Hernia 

Transcranial magnetic stimulation (TMS) is the essence of the technique, indications and contraindications for conducting. Tandem mass spectrometry in genetic screening

4, 1

1 FSBI "Medical Genetic Research Center" of the Russian Academy of Medical Sciences

2 SBEE HPE "Rostov State Medical University of the Ministry of Health of Russia"

3 GBUZ "Regional Clinical Hospital No. 1 named after Professor S.V. Ochapovsky" of the Department of Healthcare of the Krasnodar Territory

4 FSBI "Medical Genetic Research Center"

In order to justify the introduction of mass screening of newborns on hereditary diseases exchange (NBO) by tandem mass spectrometry (MS / MS), a retrospective study of archived blood samples of children (n \u003d 86) who died in the first year of life was carried out. Changes in the profiles of amino acids and acylcarnitines were detected in 4 cases (4.7%). In one of them, a multiple increase in the concentration of leucine, isoleucine and valine, which is specific to the disease of the smell of maple syrup urine, was found. Clinical picture and the detection of a mutation in the first exon of the BCKDHB gene (c.98delG) in a heterozygous state indirectly confirmed the diagnosis of leucinosis. In the other three cases, the revealed changes in the profile of amino acids and acylcarnitines are not of the same specific character. In these cases, repeated blood tests by the MS / MS method, additional clinical and biochemical studies would be necessary. As a result of the study, the necessity of introducing the MS / MS method into the programs of neonatal screening for NBO for their timely diagnosis and treatment was confirmed.

retrospective diagnosis

tandem mass spectrometry

hereditary metabolic diseases

1. Krasnopolskaya KD Hereditary metabolic diseases. Reference book for doctors. - M .: RPO "Center for social adaptation and rehabilitation of children" Fohat ", 2005. - 364 p.

2. Mikhailova S. V., Zakharova E. Yu., Petrukhin A. S. Neurometabolic diseases in children and adolescents. Diagnostics and approaches to treatment. - M .: "Literra", 2011. - 352 p.

3. Chace H. D. Rapid diagnosis of MCAD deficiency quantitative analysis of octanoylcarnitine and other acylcarnitines in newborn blood spots by tandem mass spectrometry / Chace H. D., Hillman S. L., Van Hove J. L. et al. // Clinical Chemistry. - 1997. - V. 43. - No. 11. - P. 2106-2113.

4. Nyhan L. W., Barshop B. A., Ozand P. T. Atlas of metabolic diseases. - Second edition. - London: Hodder Arnold, 2005 .-- 788 p.

5. Rashed M. S. Clinical application of tandem mass spectrometry: ten years of diagnosis and screening for inherited metabolic diseases // J. of Chrom. B. - 2001. - V. 758. - No. 27-48.

6. Sweetman L. Naming and counting disorders (counditions) included in newborn screening panels / Sweetman L., Millington D. S., Therrell B. L. et al. // Pediatrics. - 2006. - V. 117. - P. 308-314.

7. Van Hove J. L. Medium-chain acl-CoA dehydrogenase deficiency: diagnosis by acylcarnititne analysis in blood / Van Hove J. L., Zhang W., Kahler S. G. et al. // Am. J. Hum. Genet. - 1993. - V. 52. - P. 958-966.

Introduction

To date, more than 500 nosological forms of hereditary metabolic diseases (NBO) are known. The bulk of NBOs are extremely rare, but their total frequency in the population is 1: 1000-1: 5000. As a rule, NBO manifests itself in the first year of life with nonspecific symptoms that clinically mask them as another, non-hereditary somatic pathology. At the same time, the timely diagnosis of metabolic hereditary diseases is important, since for many of them, developed and continue to be developed effective methods pathogenetic treatment, without which the outcome of diseases often remains fatal. It is generally accepted that neonatal genetic screening is one of the most justified and effective approaches to early detection of hereditary pathology. The development of the method of tandem mass spectrometry (MS / MS) with electrospray ionization made large-scale mass spectrometric screening applicable in the practice of mass screening at NBO by the end of the 90s of the XX century. This highly sensitive micromethod makes it possible to simultaneously determine in several microliters of blood the concentration of tens of amino acids and acylcarnitines, which are important for the diagnosis of NBO. The effectiveness of the MS / MS laboratory test made it possible to include it in the state programs of neonatal screening of newborns for aminoacidopathy, organic aciduria and defects in mitochondrial β-oxidation of fatty acids in a number of countries. Nevertheless, in the Russian Federation, the MS / MS method has not been introduced into the system of mass screening of newborns and is available for selective screening for NBO only in single federal medical centers.

The purpose of this study was to scientifically substantiate the need to include MS / MS studies for the diagnosis of aminoacidopathies, organic acidurias, and mitochondrial β-oxidation defects of fatty acids into regional programs for mass screening of newborns based on retrospective mass spectrometric analysis of blood samples from sick children whose diseases have ended. lethal outcome in the first year of life.

Patients and research methods

This retrospective study included children (n \u003d 86, the ratio of boys: girls 48/38) who died in the first year of life (at the age of 5 days to 11 months of life) during one calendar year (2010) in the administrative territory of Krasnodar Territory ... The study included children with congenital malformations (n \u200b\u200b\u003d 29), infectious diseases - pneumonia, sepsis, bacterial meningoencephalitis (n \u003d 37), perinatal CNS damage (n \u003d 11), sudden death syndrome (n \u003d 6) and other diseases ( n \u003d 3). The control group consisted of 438 clinically healthy newborns (227 girls, 211 boys) at the age of 3-8 days. In this group, the reference values \u200b\u200bof the concentrations of amino acids and acylcarnitines in capillary blood were determined in healthy children of the neonatal period.

The material for the study was archived samples of peripheral blood on standard paper test forms, obtained at 3-8 days of life for standard neonatal screening. The concentration of amino acids and acylcarnitines (Table 1) in the blood was determined by tandem mass spectrometry (MS / MS) using an Agilent 6410 quadrupole tandem mass spectrometer (Agilent Technologies, USA) according to the certified method of the CHROMSYSTEM company No. V1 07 05 57136 001. The study was performed in the laboratory of medical genetics of the Rostov State Medical Institute of the Ministry of Health of Russia.

Table 1

Metabolites determined by MS / MS

Metabolite

Symbol

Metabolite

Symbol

A m in o k and slots

3-methylcrotonylcarntine

Aspartic acid

3-hydroxyisovalerylcarnitine

Glutamic acid

Hexanoylcarnitine

Leucine + Isoleucine

Octanoylcarnitine

Methionine

Octenoylcarnitine

Phenylalanine

Decanoylcarnitine

Decenoylcarnitine

Dodecanoylcarnitine

Myristilcarnitine

Citrulline

Tetradecenoylcarnitine

Tetradecinoylcarnitine

Hydroxymyristylcarntine

A ts and lkar n and t in s

Palmitoylcarnitine

Free carnitine

Hexadecenoylcarnitine

Acetylcarnitine

Hydroxyhexadecenoylcarnitine

Propionylcarnitine

Hydroxypalmitoylcarnitine

Malonylcarnitine

Stearoylcarnitine

Butyrylcartin

Oleoylcarnitine

Methylmalonylcarnitine

Hydroxystearoylcarnitine

Izovalerylcartin

Hydroxyoleoylcarnitine

Glutarylcarnitine

Hydroxylinoylcarnitine

Statistical processing of the obtained data was carried out using the Statistica 6.0 software package and Excel 2007 spreadsheets. To determine the descriptive numerical characteristics of the variables, standard statistical analysis methods were used: calculating the median, 0.5 and 99.5 percentiles.

For confirmatory molecular genetic diagnosis of leucinosis, DNA was isolated from dry blood spots using a DiatomDNAPrep reagent kit (Biocom LLC, Russia). The selection of primers for PCR amplification was carried out for 10 exons of the BCKDHA and BCKDHB genes. Sequencing of PCR fragments in order to detect rare mutations was carried out according to the manufacturer's protocol on an ABIPrism 3500 genetic analyzer (Applied Biosystem, USA).

Research results and discussion

As a result of the study of the concentrations of amino acids and acylcarnitines in the peripheral blood of 438 clinically healthy newborns, 0.5 and 99.5 percentile concentrations of the studied metabolites were determined, which were used by us in the future as reference values \u200b\u200b(Table 2). Comparison of the concentrations of amino acids and acylcarnitines, determined in blood samples of 86 children who died in the first year of life, with the reference concentration values, showed that in 82 patients (95.3%) none of the studied parameters exceeded 0.5 and 99, 5 percentiles of the control group, which made it possible to abandon the working version about the presence of metabolic disorders of amino acids and carnitines, which were not verified in vivo. However, in 4 children (4.7%) the concentrations of some amino acids and acylcarnitines were several times higher than the upper limits of the reference interval in the control group (Table 2).

table 2

Results of a retrospective assessment of the concentrations of amino acids and acylcarnitines in newborns (n \u200b\u200b\u003d 4) with the level of individual metabolites outside the range of 0.5-99.5 percentiles

Metabolites

Concentrations of individual metabolites (μmol / L)

Reference values \u200b\u200bof the control group (n \u003d 438)

in the range

0.5-99.5 percentiles

Individual patient values \u200b\u200b(n \u003d 4) *

Patient 1

Patient 2

Patient 3

Patient 4

A m in o k and slots

2503,868

1457,474

A ts and lkar n and t in s

* Note:

Patient 1 - a boy KM (diagnosis: obstructive bronchiolitis), died at the age of 11 months;

Patient 2 - a boy CF (diagnosis: pneumonia), died at the age of 1 month;

Patient 3 - female PV (diagnosis: sepsis), died at the age of 12 days.

Patient 4 - girl PA (diagnosis: pneumonia), died at the age of 6 days.

In the first case, in a CM patient who died at the age of 11 months with a diagnosis of obstructive bronchiolitis, tandem mass spectrometry of amino acids and acylcarnitines in archived blood samples revealed changes in the content of leucine, isoleucine and valine, which are quite specific in nature to speak of a high probability of congenital a metabolic defect in the pathway of leucine and isoleucine catabolism. In the studied archival blood samples, an increase in the concentration of leucine and isoleucine by more than 9 times and of valine by more than 3 times compared with the reference values \u200b\u200bwas found, which suggests the diagnosis of a disease with the smell of maple syrup urine.

From the available clinical data in favor of leucinosis in a BM child, the following clinical manifestations were evidenced: early rejection of breastfeeding, symptoms of neonatal encephalopathy, an increase in neurological symptoms - changes in muscle tone, seizures, epilepsy, delayed psychomotor development. The child often had infectious diseases respiratory tract with a severe course, which caused obliterating bronchiolitis, which was the cause of death at the age of 11 months. We do not have information about whether the child had a specific urine odor, but an increase in the concentration of metabolites typical for leucinosis and characteristic clinical symptoms confirm our assumption. In addition, the diagnosis of the disease of maple syrup urine odor is supported by the results of the DNA diagnosis of leucinosis using archived blood samples. Molecular genetic analysis revealed in the child a deletion of c.98delG in the first exon of the BCKDHB gene in a heterozygous state. The same mutation is found in the mother's blood. Due to the limited number of archived blood samples of the child and the inaccessibility of biological material from his father, the second mutation could not be detected. However, a combination of clinical, biochemical, and molecular genetic data supports the diagnosis of leucinosis (or maple syrup urine-smelling disease, MIM ID 248600) in the case studied.

In the other three cases, the revealed changes in the profile of amino acids and acylcarnitines are not of the same specific character as in the previous case. It is impossible to assume certain NBOs based on MS / MS data, and even more so to assert with certainty, in these cases. For the differential diagnosis of aminoacidopathies and organic acidurias, repeated blood tests by the MS / MS method, additional clinical and biochemical studies would be necessary.

The increase in disease-specific metabolites is variable and depends on many factors. Child's eating habits, taking some drugs should be considered when interpreting the results. So, taking drugs containing valproic acid or medium-chain triglycerides leads to an increase in C6, C8 and C10, which complicates the diagnosis of medium-chain acyl-CoAdehydrogenase deficiency. Taking carnitine-containing drugs can also lead to increased concentrations of short- and medium-chain acylcarnitines. The content of long-chain acylcarnitines in plasma and whole blood different, since they are associated with the membranes of erythrocytes, therefore, the hematocrit has a certain value. With some exceptions, one and a half to two-fold increase in concentration requires a second blood test. Thus, the levels of metabolites pathognomonic for propionic and isovalerian aciduria usually increase by more than 5 times, and even a slight change in the concentration of glutarylcarnitine requires not only a repeated blood test, but also additional research. organic acids urine characteristic of type I glutaric aciduria.

Conclusion

A retrospective study of blood samples from young children who died from various reasons, made it possible to assume in some cases hereditary metabolic pathology. In one of them, the diagnosis of the disease was confirmed by the smell of maple syrup urine (leucinosis). Timely diagnostic measures in such cases are an important component in differential diagnosis congenital metabolic errors. The study of the concentrations of amino acids and acylcarnitines in samples of biological fluids can be of diagnostic value in the analysis of cases of infant mortality. The posthumous diagnosis of hereditary metabolic disease in a deceased child is an indication for medical genetic counseling of the family. It is necessary to widely implement the MS / MS method in neonatal screening as the main tool for detecting aminoacidopathies, organic acidemias and defects in β-mitochondrial fatty acid oxidation in newborns for the timely diagnosis and treatment of NBO.

Reviewers:

Polevichenko Elena Vladimirovna, dr honey... Sci., Professor, Chief Researcher of the Department of Rehabilitation and Medical and Social Assistance of the Federal State Budgetary Institution "Federal Research Center for Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev" of the Ministry of Health of Russia, Moscow.

Mikhailova Svetlana Vitalievna, Dr. med. Sci., Head of the Department of Medical Genetics, Russian Children's Clinical Hospital of the Ministry of Health of Russia, Moscow.

Bibliographic reference

Baydakova G.V., Antonets A.V., Golikhina T.A., Matulevich S.A., Amelina S.S., Kutsev S.I., Kutsev S.I. RETROSPECTIVE DIAGNOSTICS OF HEREDITARY DISEASES OF EXCHANGE BY THE METHOD OF TANDEM MASS SPECTROMETRY // Modern problems of science and education. - 2013. - No. 2 .;
URL: http://science-education.ru/ru/article/view?id\u003d8953 (date of access: 12.12.2019). We bring to your attention the journals published by the "Academy of Natural Sciences"

MINISTRY OF HEALTH OF SVERDLOVSK REGION

ORDER

ON THE DIAGNOSIS OF HEREDITARY METABOLIC DISEASES IN CHILDREN BY THE METHOD OF TANDEM MASS SPECTROMETRY ON THE TERRITORY OF THE SVERDLOVSK REGION

In accordance with the Order of the Ministry of Health of the Russian Federation of 15.11.2012 N 917n "On approval of the Procedure for providing medical care to patients with congenital and (or) hereditary diseases", in order to early detection of hereditary metabolic diseases, prevention of disability, and reduction of mortality from hereditary diseases

i order:

1. Approve:

1) Indications for referral of children of the Sverdlovsk region to the diagnosis of hereditary metabolic diseases by the method of tandem mass spectrometry (TMS) (Appendix No. 1);

2) Protocol for examining children for hereditary diseases metabolism by the TMS method (Appendix No. 2);

3) form of the form for referral for laboratory research by the TMS method (Appendix No. 3);

4) Form of the survey result form (Appendix N 4).

2. To the heads of state healthcare institutions of the Sverdlovsk region:

1) ensure the examination of children according to the indications in accordance with Appendix No. 1 to this Order;

2) introduce the Protocol for the examination of children for hereditary metabolic diseases using the TMS method in accordance with Appendix No. 2 to this Order;

3) ensure the delivery of test forms in accordance with the Protocol for the examination of children for hereditary metabolic diseases by the TMS method in the GBUZ SO "Clinical and Diagnostic Center" Maternal and Child Health Protection "(Yekaterinburg, Flotskaya st., 52, tel. / fax 374-31-10);

3. To recommend to the director of the Ural Research Institute of Maternity and Infancy Protection of the Ministry of Health of Russia NV Bashmakova, to the head of the Health Department of the Administration of Yekaterinburg A.A. Dornbusch:

1) ensure the examination of children according to the indications in accordance with Appendix No. 1;

2) implement the Protocol for the examination of children for hereditary metabolic diseases using the TMS method in accordance with Appendix No. 2;

3) ensure the delivery of test forms in accordance with the Protocol for screening children for hereditary metabolic diseases using the TMS method;

4) ensure the routing of children with a high risk of hereditary metabolic diseases who need additional examination, clarification of the diagnosis on call to the GBUZ SO "Clinical and Diagnostic Center" Maternal and Child Health Protection "within 48 hours.

4. Chief physician GBUZ SO "Clinical and Diagnostic Center" Maternal and Child Health Protection "Nikolaeva EB to ensure:

1) examination of children of the Sverdlovsk region for hereditary metabolic diseases by the TMS method in the laboratory of neonatal screening GBUZ SO "Clinical and Diagnostic Center" Maternal and Child Health Protection "(Appendix No. 2);

2) confirmatory diagnostics in the laboratory of molecular genetic studies for a number of hereditary metabolic diseases, taking into account the results of examining children by the method of tandem mass spectrometry;

3) carrying out medical and genetic counseling of families based on the results of the examination. If necessary, referral for research to federal centers in accordance with paragraphs 16, 17 of the Procedure for providing medical care patients with congenital and (or) hereditary diseases, approved by the Order of the Ministry of Health of the Russian Federation dated 12.11.2012 N 917n "On approval of the Procedure for providing medical care to patients with congenital and (or) hereditary diseases";

4) provision of advisory specialized medical care, including dispensary observation, to children with identified pathology.

5. To the chief physician GBUZ SO "Regional Children's Clinical Hospital N 1" SR Belomestnov. to ensure the provision of consultative and diagnostic and inpatient care to children with hereditary metabolic diseases who need additional examination, clarification of the diagnosis, treatment in the direction of GBUZ SO "Clinical and Diagnostic Center" Maternal and Child Health Protection ".

6. Responsibility for the implementation of this Order shall be assigned to the head of the department for the organization of medical care for mothers and children of the Ministry of Health of the Sverdlovsk Region, SV Tatareva.

8. A copy of this Order should be sent within 7 days to the Main Directorate of the Ministry of Justice in the Sverdlovsk Region.

9. Control over the implementation of this Order shall be entrusted to the Deputy Minister of Health of the Sverdlovsk Region Zholobova E.S.

Minister of Health
Sverdlovsk region
A.R.Belyavsky

Appendix N 1. INDICATIONS FOR REFERRING CHILDREN TO DIAGNOSTICS OF HEREDITARY DISEASES OF METABOLIC METHOD BY TANDEM MASS SPECTROMETRY (TMS)

Appendix N 1
to the Order
Ministry of Health
Sverdlovsk region


The method of tandem mass spectrometry (TMS) reveals hereditary metabolic diseases:

1) amino acids: phenylketonuria, disease with the smell of urine maple syrup (leucinosis), homocystinuria, hyperornithinemia, ornithine trascarbamylase deficiency, hyperprolinemia, hyperornithinemia-hyperammonemia-homocytrullinemia syndrome, arginine succinase deficiency, cytrulethioninemia, hyperprolinemia

2) organic acids: methylmalonic, propionic, isovaleric acidemias, glutaric aciduria type I, biotinidase deficiency, 3-methylcrotonylglycinuria, holocarboxylase synthetase deficiency;

3) defects of mitochondrial beta-oxidation of fatty acids: short-chain acyl-CoA dehydrogenase deficiency, medium-chain acyl-CoA dehydrogenase deficiency, primary carnitine deficiency / carnitine transport defect, carnitine palmitoyltransferase deficiency of I and II types, acyl Acyl-CoA dehydrogenase deficiency very long-chain acyl-CoA dehydrogenase, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, mitochondrial trifunctional protein deficiency, carnitine acylcarnitine translocase deficiency, beta-ketothiolase deficiency, hydroxymethyl-lytarylase deficiency.

In addition, secondary changes in the spectrum of amino acids can be detected: prolinemia, hyperalaninemia, and others.

Indications for referring children to the diagnosis of hereditary metabolic diseases by tandem mass spectrometry:

1) similar cases of the disease in the family;

2) cases of sudden death of a child at an early age in the family;

3) a sharp deterioration after a short period of normal development of the child. The asymptomatic interval can range from several hours to several weeks and depends on the nature of the defect, diet and other factors;

4) unusual body odor and / or urine ("sweet", "mouse", "boiled cabbage", "the smell of sweaty feet", etc.);

5) features of the phenotype: hypopigmentation, facial dysmorphia and congenital defects development in combination with neurological pathology, delayed physical development of unknown etiology;

6) neurological disorders - impaired consciousness (depression syndrome, lethargy, coma), generalized, less often focal seizures, changes in muscle tone (diffuse muscle hypotension or spastic tetraparesis), coordination disorders, ophthalmoplegia, delayed psychomotor development of an unknown cause. Neurological symptoms often combined with respiratory rhythm disturbances (distress syndrome, bradypnea, tachypnea, apnea, irregular breathing, hiccups);

7) violations from other organs and systems (violation of sucking, swallowing, refusal to eat, vomiting and regurgitation syndrome, dehydration, jaundice, hepatomegaly, liver cirrhosis, hepatosplenomegaly, liver dysfunction, cardiomyopathy, renal tubular dysfunction, hemorrhagic syndrome, cataract, retinopathy);

8) reye-like syndrome;

9) changes in blood and urine parameters - thrombocytopenia, neutropenia, anemia, metabolic ketoacidosis / acidosis, respiratory alkalosis, hypoglycemia / hyperglycemia, bouts of hyperammonemia, lactic acidosis, increased activity of liver enzymes and creatine phosphokinase levels, ketonuria, myoglobinuria.

Appendix N 2. PROTOCOL OF EXAMINATION OF CHILDREN FOR HEREDITARY DISEASES OF METABOLISM METHOD BY TMS

Appendix N 2
to the Order
Ministry of Health
Sverdlovsk region
dated November 10, 2015 N 1769-p


This Protocol regulates the organization of government agencies Healthcare of the Sverdlovsk region examination of children for hereditary metabolic diseases by tandem mass spectrometry (TMS) for the purpose of their early detection, timely treatment, prevention of disability and the development of severe clinical consequences, as well as reducing infant mortality from hereditary diseases. The protocol for examining children for hereditary metabolic diseases is regulated by the Procedure for the provision of medical care to patients with congenital and (or) hereditary diseases, approved by Order of the Ministry of Health of the Russian Federation of November 12, 2012 N 917n "On approval of the Procedure for providing medical care to patients with congenital and (or) hereditary diseases ".

According to the indications according to Appendix No. 1 to this Order, children who are in the departments of pathology of newborns, intensive care units, intensive care, infectious, gastroenterological, neurological, pediatric, endocrinological departments are subject to examination.

A referral for laboratory research by the TMS method is drawn up in accordance with Appendix No. 3 to this Order.

The collection of blood samples from children is carried out by a specially trained responsible medical officer.

Blood sampling is performed in the morning, on an empty stomach (2 hours after feeding for infants), if the child requires a blood transfusion, it is preferable to take blood before the transfusion or 48 hours after the transfusion.

Blood sampling from children is carried out only on special test forms issued by the neonatal screening laboratory of the Clinical and Diagnostic Center "Maternal and Child Health Protection", with the control of the expiration date of the test forms.

The following information about the child is recorded on the form:

Territory;

The name of the medical institution and department;

Surname, name, patronymic of the child;

Date of birth of the child;

Date of taking the child's blood;

Child's condition (diagnosis);

Contact phone number of the child's parents;

Name of the person who took the blood.

The lettering on the letterhead should be written in a ballpoint pen clearly and legibly. The inscription should not touch blood stains.

Capillary blood sampling technique:

Wipe the puncture area with a sterile cloth dampened with 70% alcohol. Dry with a dry, sterile tissue (to avoid blood hemolysis);

Use an automatic disposable scarifier (guillotine type) to puncture the skin. Remove the first drop after cutting the skin with a dry sterile napkin;

With gentle massage movements, promote the accumulation of a second drop of blood, apply it to a special test blank. Pay attention that from the front and from the seamy side the stain looks equally bright and uniform, without white blotches of paper and caked areas;

Apply 5 blood spots this way. It is unacceptable to saturate the same area twice. The blood stains must be at least the size indicated on the form. If not enough blood is obtained, the piercing should be repeated. The accuracy and reliability of the study depends on the quality of blood sampling!

The blood sample is dried horizontally on a dry, clean, fat-free surface until completely dry for at least 2 hours, without the use of additional heat treatment and avoiding direct sunlight. Do not allow the forms to touch each other during drying.

Dried test blanks are packed, without touching stains, in a clean envelope to avoid contamination and in special packaging in compliance with the temperature regime (+2 - +8 degrees C) are delivered for research to the Clinical Diagnostic Center. and baby "within 48 hours.

A trained medical professional who fills out a special filter paper test form is responsible for the correctness of blood sampling and the reliability of the specified information.

Test forms are delivered for research to the Clinical and Diagnostic Center "Maternal and Child Health Protection" (52, Flotskaya st.) By courier in a thermal container in compliance with the temperature regime (+2 - +8 degrees C).

Reception of blood samples in the laboratory department of the GBUZ SO "Clinical and Diagnostic Center" Protection of the Health of the Mother of the Child "is carried out from 8-00 to 15-00 (Monday - Friday), from 8-00 to 14-00 (Saturday), on holidays - on a special schedule.

Laboratory tests of children's blood samples are carried out in the neonatal screening laboratory of the Clinical and Diagnostic Center "Maternal and Child Health Protection" within 10 days after the delivery of the blood sample.

The result of the examination is reported to the attending physician by phone and in electronic form / fax to the referring healthcare facility in accordance with the approved form (Appendix No. 4).

In GBUZ SO "Clinical and Diagnostic Center" Maternal and Child Health Protection "children are provided with medical and genetic counseling with additional molecular genetic or biochemical studies, depending on nosology. Research is carried out on the basis of existing laboratories GBUZ SO" Clinical Diagnostic Center " maternal and child health ". Based on the results of the analyzes obtained and additional studies, the final diagnosis is made and treatment is prescribed. If necessary, medical genetic counseling is carried out in the mode of telemedicine consultations.

In the direction of the GBUZ SO "Clinical and Diagnostic Center" Protection of the Mother's of the Child ", a child in need of additional examination and clarification of the diagnosis of a hereditary disease is hospitalized in the State Budgetary Healthcare Institution of the Regional Children's Clinical Hospital No. 1.

If it is necessary to establish a final diagnosis in connection with the atypical course of the disease, the lack of effect from the therapy with the likely effectiveness of other methods of treatment, the need for additional examination in diagnostically difficult cases, specialized medical care is provided in federal state medical organizationsadministered by the Ministry of Health of the Russian Federation.

When a diagnosis of a hereditary disease from a group of rare diseases detected by tandem mass spectrometry is established, a geneticist individually draws up an application for the necessary medical nutrition or drug supply for a sick child and is transferred to the department of drug supply organization and pharmaceutical activities of the Ministry of Health of the Sverdlovsk Region, treatment is carried out at the expense of the regional budget.

Laboratory control of the treatment of sick children, medical and genetic counseling, and subsequent prenatal diagnosis of a family with a child with a hereditary disease is carried out by the Clinical Diagnostic Center “Maternal and Child Health”.

Appendix N 3. FORM OF THE FORM FOR SENDING FOR A LABORATORY STUDY BY THE METHOD OF TANDEM MASS SPECTROMETRY

Appendix N 3
to the Order
Ministry of Health
Sverdlovsk region
dated November 10, 2015 N 1769-p

┌═════════════════════════════════════════════════════════════════════════‰

│ directing institution, branch │
│ │
│ DIRECTION │
│ │
│ In GBUZ SO "Clinical and Diagnostic Center" Maternal Health │
│ and a child "for testing for hereditary diseases │
│ Metabolism by tandem mass spectrometry │
│ │
│ Full name patient _______________________________________________________ │
│ Date of birth __ / __ / ____ │
│ Full name mother _________________________________________________________ │
│ Residence ______________________________________________________ │
│ Contact phone number of parents __________________________________________ │
│ Diagnosis _______________________________________________________________ │
│ _______________________________________________________________________ │
│ _______________________________________________________________________ │
│ Full name doctor __________________________________________________________ │
│ Phone of the attending physician ________________________________________________ │
│ Date and time of blood sampling __ / __ / ____ │
│ │
│ Date of referral Doctor's signature, transcript Doctor's stamp │
│ │
└═════════════════════════════════════════════════════════════════════════…

Appendix N 4. FORM OF RESULTS FOR RESULTS BY TANDEM MASS SPECTROMETRY

Appendix N 4
to the Order
Ministry of Health
Sverdlovsk region
dated November 10, 2015 N 1769-p

GBUZ SO "Clinical and Diagnostic Center" Maternal and Child Health Protection "Yekaterinburg, 52 Flotskaya st. Laboratory of neonatal screening Tel. 374-31-10

Date of Birth

Date of blood collection

The patient's biological material (blood) was examined by tandem mass spectrometry

CONCLUSION

According to the results of a study of data for hereditary aminoacidopathies, organic aciduria and defects in beta-oxidation of fatty acids, were not identified.

__ / __ / ____ Head LNS ______________

In the epoch of modern times with the flourishing of natural-scientific thought, special attention was paid to "animal electricity". Inquiring minds were agitated by the experiments of Luigi Galvani, which caused the frog's leg to contract. Later, with the advent of the "voltaic pillar", everyone who considers himself modern man and a natural scientist, conducted similar experiments. Physical properties muscle tissue was examined with the help of a current, and the apotheosis of "similarity to the Creator" was considered an experiment in which a direct current pulse forced the muscles of a corpse to contract.

With the development of electrical engineering and the advent of Faraday's experiments, new equipment appeared that made it possible to obtain magnetic fields using current, and vice versa. So, the idea of \u200b\u200busing not directly an electric current, but a magnetic field to influence parts of the cerebral cortex was gradually born. After all, a magnetic field creates an electric current, and it already causes various processes in the body. It was from this idea that the method called transcranial magnetotherapy was born. What is it, and how does science define it?

Definition

TCMS, or transcranial magnetic stimulation, is a method used in scientific and clinical practice that allows to stimulate the cerebral cortex at a distance without pain and directing an electric current magnetic field, receiving various responses to the impact of short pulses of a magnetic field. This method is used for both diagnosis and treatment of certain types of diseases.

The essence of the technique and mechanism of action

The device for electromagnetic brain stimulation is based on the principle of electromagnetic induction excitation. The property of the current passing through the inductor is known to generate a magnetic field. If we select the characteristics of the current and the coil so that the magnetic field is strong and the eddy currents are minimal, then we will have the TKMS apparatus. The basic sequence of events might be:

The device block generates pulses of high-amplitude currents, discharging the capacitor when a high-voltage signal closes. The capacitor is distinguished by high amperage and high voltage - these specifications are very important for obtaining strong fields.

These currents are directed into a hand-held probe, on which a magnetic field generator - an inductor - is located.

The probe travels very close to the scalp, so the generated magnetic field up to 4 Tesla is transmitted to the cerebral cortex.

Modern inductors are forced-cooled because they still get very hot due to eddy currents. Do not touch the patient's body with them - you can get burned.

Four tesla is a very impressive figure. Suffice it to say that this exceeds the power of a high-field MRI scanner, which gives 3 T each on a large ring of electromagnets. This value is comparable with the data of large dipole magnets of the Large Hadron Collider.

Stimulation can be performed in different modes - single-phase, two-phase, and so on. You can choose the type of inductor coil that allows you to give a differently focused magnetic field to different depths of the brain.

In the bark are generated secondary processes - depolarization of neuronal membranes and generation of electrical impulses. The TMS method allows, by moving the inductor, to achieve stimulation of different parts of the cortex and get a different response.

Transcranial magnetic stimulation requires interpretation of the results. A series of different impulses are sent to the patient, and the result is the identification of the minimum threshold of the motor response, its amplitude, delay time (latency) and other physiological parameters.

If the doctor acts on the cortex, as a result, the muscles of the trunk can contract according to the "motor homunculus", that is, in accordance with the cortical representation of the muscles of the motor zone. This is the MEP, or motor evoked potentials.

If at the same time the sensors are placed on the desired muscle and electroneuromyography is performed, then it is possible to "ring out" the nervous tissue taking into account the characteristics of the induced impulse.

Indications for the procedure

In addition to the research function, the "artificial" impulse created by neurons can provide curative action with muscle diseases. In children with cerebral palsy, the TCMS procedure stimulates muscle development, has positive effect with spasticity. Transcranial magnetic stimulation is used to diagnose and treat the following diseases:

  • multiple sclerosis and other demyelinating diseases;
  • cerebral atherosclerosis, diffuse vascular lesions of the brain;
  • the consequences of injuries and trauma to the brain and spinal cord;
  • radiculopathies, myelopathies, lesions of the cranial nerves (Bell's palsy);
  • parkinson's disease and secondary parkinsonism;
  • various dementias (Alzheimer's).

In addition, the method of transcranial magnetic stimulation can help in the diagnosis of speech disorders, for problems associated with neurogenic bladder, with angiocephalgia (migraine) and epilepsy.

Solid experience (mostly foreign) has been accumulated when this technique is used for depression, affective states and neuroses. Helps TCMS and obsessive-compulsive conditions ( obsessive-compulsive disorder). Its course application helps to eliminate psychotic symptoms in exacerbations of schizophrenia, as well as in various hallucinations.

But this method, which uses strong magnetic fields, cannot but have contraindications.

Contraindications

Despite the fact that TCMS is a non-invasive technique, strong magnetic fields are its effectors. It should be remembered that, unlike MRI, where the entire human body is exposed to a powerful magnetic field, transcranial magnetotherapy generates it at a distance of several centimeters. There are a number of serious and even absolute contraindications to its implementation, for example, ferromagnetic materials inside the skull (implants), or hearing aids. A pacemaker is also a contraindication, but theoretical, since it can only accidentally be in the zone of the magnetic field.

Nowadays there are devices for deep brain stimulation, for example, in Parkinson's disease. In this case, the procedure is also contraindicated.

Clinical contraindications include:

  • focal formations of the central nervous systemthat can cause seizures;
  • the appointment of funds that can increase the excitability of the cerebral cortex (and receive a synchronous discharge);
  • traumatic brain injury with prolonged loss of consciousness;
  • anamnestically - a seizure or epilepsy, epic activity on the encephalogram;
  • increased intracranial pressure.

As can be seen from the above, the main danger is to get a synchronous hemispheric or total focus of excitation of cortical neurons, or an epileptic seizure.

About side effects

It would be naive to think that such a serious effect as the secondary induction of the neural action potential by a strong magnetic field can proceed without any side effects... The most common conditions include:

  • stomach discomfort and nausea;
  • fear of unexpected muscle contractions;
  • redness of the skin;
  • temporary loss of speech (with stimulation of Broca's zone), often accompanied by violent laughter;
  • pain in the muscles of the head and face;
  • dizziness and tiredness;
  • temporary hearing loss.

Also, the device is used with extreme caution when working with children. When stimulating a child's motor acts, it is difficult to expect complete control and relaxation from him. There is a danger that if the probe with the coil is accidentally held near the heart, the device may cause disturbances in the heart rhythm. Usually, the magnetic field causes extrasystole, and no help is needed. But in patients with atrial fibrillation, with thyrotoxicosis, this can lead to a worsening of the condition.

For many years, screening has mainly been done testsspecific for each individual disease. For example, PKU screening was based on microbiological or chemical assessment of an increase in phenylalanine.

This situation has completely changed in the last decade with the advent of tandem mass spectrometry (TMS) technology. Tandem mass spectrometry (TMS) analysis can not only accurately and quickly detect elevated phenylalanine in a blood spot in a newborn with fewer false positives compared to older methods, but also simultaneously detect several dozen other biochemical abnormalities.

Some of them have already screened individual tests... For example, many states have used specific tests to detect elevations in methionine to detect Tandem mass spectrometry (TMS) has also proven to be a reliable method for non-natal screening for certain diseases that meet screening criteria but lack a previously reliable test.

For example, insufficiency of MCAD - a disease of fatty acid oxidation, usually asymptomatic, but clinically detectable when the patient has increased catabolism. Detection of MCAD deficiency at birth can be vital because sick children have a very high risk of life-threatening hypoglycemia in early childhood in catabolic conditions caused by intercurrent diseases such as viral infection.

Almost a quarter of children with undiagnosed MCAD deficiency die on the first episode. When correct treatment the metabolic disorder can be stopped. If MCAD is insufficient, the primary goal of screening is to warn parents and doctors about the risk of metabolic decompensation, since children are practically healthy between attacks and do not need daily treatment, except to exclude prolonged fasting.

Still use tandem mass spectrometry (TMS) for neonatal screening remains questionable. In addition to providing rapid testing of many disorders for which neonatal screening is already being done or may be warranted, tandem mass spectrometry (TMS) also detects newborns with congenital metabolic errors such as methylmalonic acidemia, which are usually not included in screening programs due to their rarity and difficulty in providing definitive therapythat protects against progressive neurological deterioration.

Diseases Detected by Tandem Mass Spectrometry

I. Aminoacidemias:
- PKU
- Urine disease with a maple syrup smell
- Homocystinuria
- Citrullinemia
- Arginine amber aciduria
- Tyrosinemia type I

II. Organic acidemia:
- Propionic acidemia
- Methylmalonic acidemia
- Isovalerian acidemia
- Isolated 3-methyl-crotonyl-glycinemia
- Glutaric acidemia (type I)
- Deficiency of mitochondrial acetoacetyl-coA-thiolase
- Hydroxymethylglutaric acidemia
- Lack of many coA carboxylases

III. Fatty acid oxidation disorders:
- Insufficient SCAD
- Lack of hydroxy-SCAD
- Lack of MCAD
- Insufficiency of VLCAD
- LCAD deficiency and trifunctional protein deficiency
- Glutaric acidemia type II
- Lack of carnitine palmitoyltransferase II

Tandem mass spectrometry (TMS) can also identify abnormal metabolites of undetermined health significance. For example, SCAD deficiency is another fatty acid oxidation disorder that is most often asymptomatic, although some patients may have difficulty with episodic hypoglycemia. Thus, the predictive value of a positive tandem mass spectrometry (TMS) assay for symptomatic SCAD is likely to be very low.

Does the advantage of detection outweigh sCAD deficiencies negative effect of the test, causing undue concern to parents, for the majority of newborns with a positive test result, who never showed clinical symptoms? Thus, not every disease detected by tandem mass spectrometry (TMS) meets the criteria for neonatal screening.

This is why some experts the health system is arguing that parents and doctors should only be told about abnormalities in metabolites with proven clinical benefit. Others advocate the use of all the information provided by tandem mass spectrometry (TMS) and suggest that parents and doctors should be informed about all abnormal metabolites, regardless of how well the disease meets the standard criteria for neonatal screening. Patients with anomalies of unknown significance can then be closely monitored. For all these reasons, the use of tandem mass spectrometry (TMS) in newborn screening remains a matter of debate.

For population screening In the prenatal period, two tests are commonly used: chromosomal analysis in older women and maternal serum AFP or triple NTD and chromosomal aneuploidy.

If pregnancy is at risk from an invasive procedure for prenatal diagnosis of chromosomal aneuploidy due to maternal age, additional testing should also be offered, such as determining the AFP level in amniotic fluid, genome-wide comparative hybridization to search for dangerous submicroscopic deletions, screening for mutations in cystic fibrosis and other common diseases.


[06-225 ] Blood test for amino acids (32 indicators)

5645 RUB

To order

Amino acids are important organic substances in the structure of which there are carboxyl and amine groups. A comprehensive study that determines the content of amino acids and their derivatives in the blood reveals congenital and acquired disorders of amino acid metabolism.

* Study composition:

  1. Alanine (ALA)
  2. Arginine (ARG)
  3. Aspartic acid (ASP)
  4. Citrulline (CIT)
  5. Glutamic acid (GLU)
  6. Glycine (GLY)
  7. Methionine (MET)
  8. Ornithine (ORN)
  9. Phenylalanine (PHE)
  10. Tyrosine (TYR)
  11. Valine (VAL)
  12. Leucine (LEU)
  13. Isoleucine (ILEU)
  14. Hydroxyproline (HPRO)
  15. Serine (SER)
  16. Asparagine (ASN)
  17. Glutamine (GLN)
  18. Beta-alanine (BALA)
  19. Taurine (TAU)
  20. Histidine (HIS)
  21. Threonine (THRE)
  22. 1-methylhistidine (1MHIS)
  23. 3-methylhistidine (3MHIS)
  24. Alpha-aminobutyric acid (AABA)
  25. Proline (PRO)
  26. Cystathionine (CYST)
  27. Lysine (LYS)
  28. Cystine (CYS)
  29. Cysteic acid (CYSA)

Synonyms Russian

Screening for aminoacidopathies; amino acid profile.

Synonymsenglish

Amino Acids Profile, Plasma.

Methodresearch

High performance liquid chromatography.

What biomaterial can be used for research?

Venous blood.

How to properly prepare for the study?

  • Eliminate alcohol from the diet for 24 hours before the study.
  • Do not eat for 8 hours before the study, you can drink clean non-carbonated water.
  • Completely exclude taking medications within 24 hours before the study (as agreed with the doctor).
  • Eliminate physical and emotional stress for 30 minutes before the study.
  • Do not smoke for 30 minutes prior to examination.

General information about the study

Amino acids are organic substances containing carboxyl and amine groups. About 100 amino acids are known, but only 20 are involved in protein synthesis. These amino acids are called "proteinogenic" (standard) and, if possible, synthesis in the body are classified into nonessential and irreplaceable. Essential amino acids include arginine, valine, histidine, isoleucine, leucine, lysine, methionine, threonine, tryptophan, phenylalanine. Replaceable amino acids are alanine, asparagine, aspartate, glycine, glutamate, glutamine, proline, serine, tyrosine, cysteine. Proteinogenic and non-standard amino acids, their metabolites are involved in various metabolic processes in the body. An enzyme defect at various stages of the transformation of substances can lead to the accumulation of amino acids and their conversion products, and have a negative effect on the state of the body.

Amino acid metabolism disorders can be primary (congenital) or secondary (acquired). Primary aminoacidopathies are usually inherited autosomal recessively or linked to the X chromosome and manifest early childhood... Diseases develop due to a genetically determined deficiency of enzymes and / or transport proteins associated with the metabolism of certain amino acids. More than 30 variants of aminoacidopathies are described in the literature. Clinical manifestations can range from mild benign disorders to severe metabolic acidosis or alkalosis, vomiting, delay mental development and growth, lethargy, coma, sudden infant death syndrome, osteomalacia, and osteoporosis. Secondary disorders of amino acid metabolism can be associated with diseases of the liver, gastrointestinal tract (for example, ulcerative colitis, Crohn's disease), kidneys (for example, Fanconi syndrome), inadequate or inadequate nutrition, neoplasms. Early diagnosis and timely treatment can prevent the development and progression of disease symptoms.

This study allows to comprehensively determine the concentration in the blood of standard and non-proteinogenic amino acids, their derivatives and assess the state of amino acid metabolism.

Alanin (ALA) is able to be synthesized in the human body from other amino acids. It is involved in the process of gluconeogenesis in the liver. According to some reports, an increased content of alanine in the blood is associated with an increase in blood pressure, body mass index,.

Arginine (ARG) depending on age and functional state organism refers to the semi-essential amino acids. Due to the immaturity of enzyme systems, premature babies are not capable of its formation, therefore they need an external source of this substance. Increased demand for arginine occurs during stress, surgery, and trauma. This amino acid is involved in cell division, wound healing, hormone release, nitric oxide and urea formation.

Aspartic acid (ASP) can be formed from citrulline and ornithine and is a precursor of some other amino acids. Aspartic acid and asparagine (ASN)participate in gluconeogenesis, the synthesis of purine bases, nitrogen metabolism, the function of ATP synthetase. In the nervous system, asparagine plays the role of a neurotransmitter.

Citrulline (CIT) can be formed from ornithine or arginine and is an important component of the urea cycle in the liver (ornithine cycle). Citrulline is found in filaggrin, histones and plays a role in autoimmune inflammation in rheumatoid arthritis.

Glutamic acid (GLU) - a nonessential amino acid, which is of great importance in nitrogen metabolism. Free glutamic acid is used in the food industry as a flavor enhancer. Glutamic acid and glutamateare important excitatory neurotransmitters in the nervous system. A decrease in glutamate release is noted in classical phenylketonuria.

Glycine (GLY) is a nonessential amino acid that can be formed from serine by pyridoxine (vitamin B6). It takes part in the synthesis of proteins, porphyrins, purines and is an inhibitory mediator in the central nervous system.

Methionine (MET) - an essential amino acid, the maximum content of which is determined in eggs, sesame, cereals, meat, fish. Homocysteine \u200b\u200bcan be formed from it. Deficiency of methionine leads to the development of steatohepatitis.

Ornithine (ORN) is not encoded by human DNA and is not involved in protein synthesis. This amino acid is formed from arginine and plays a key role in the synthesis of urea and the elimination of ammonia from the body. Ornithine-containing preparations are used to treat cirrhosis, asthenic syndrome.

Phenylalanine (PHE) - an essential amino acid, which is a precursor of tyrosine, catecholamines, melanin. A genetic defect in the metabolism of phenylalanine leads to the accumulation of amino acids and its toxic products and the development of aminoacidopathy - phenylketonuria. The disease is associated with impaired mental and physical development, seizures.

Tyrosine (TYR) enters the body with food or is synthesized from phenylalanine. It is a precursor of neurotransmitters (dopamine, norepinephrine, adrenaline) and melanin pigment. With genetic disorders of tyrosine metabolism, tyrosinemia occurs, which is accompanied by damage to the liver, kidneys and peripheral neuropathy. Important differential diagnostic value has the absence of an increase in the level of tyrosine in the blood in phenylketonuria, in contrast to some other pathological conditions.

Valine (VAL), Leucine (LEU)and isoleucine (ILEU) - essential amino acids, which are important sources of energy in muscle cells. With fermentopathies, which disrupt their metabolism and lead to the accumulation of these amino acids (especially leucine), there is "maple syrup disease" (leucinosis). The pathognomonic symptom of this disease is the sweet smell of urine, which resembles maple syrup. Symptoms of aminoacidopathy begin at an early age and include vomiting, dehydration, lethargy, hypotension, hypoglycemia, seizures and opisthotonus, ketoacidosis, and central nervous system abnormalities. The disease is often fatal.

Hydroxyproline (HPRO) is formed by hydroxylation of proline under the influence of vitamin C. This amino acid ensures the stability of collagen and is its main component. With a deficiency of vitamin C, the synthesis of hydroxyproline is disrupted, the stability of collagen decreases and damage to the mucous membranes occurs - symptoms of scurvy.

Serine (SER) is a part of almost all proteins and is involved in the formation of active centers of many enzymes in the body (for example, trypsin, esterases) and the synthesis of other nonessential amino acids.

Glutamine (GLN) is a partially non-essential amino acid. The need for it increases significantly with injuries, some gastrointestinal diseases, intense physical exertion. It takes part in nitrogen metabolism, purine synthesis, regulation of acid-base balance, and performs a neurotransmitter function. This amino acid accelerates the healing and recovery processes after injuries and surgeries.

Gamma Aminobutyric Acid (GABA) synthesized from glutamine and is the most important inhibitory neurotransmitter. GABA drugs are used to treat a variety of neurological disorders.

Beta-aminoisobutyric acid (BAIBA) is a metabolic product of thymine and valine. An increase in its level in the blood is observed with a deficiency of beta-aminoisobutyrate-pyruvate aminotransferase, starvation, lead poisoning, radiation sickness and some neoplasms.

Alpha Aminobutyric Acid (AABA) - a precursor of the synthesis of ophthalmic acid, which is an analogue of glutathione in the lens of the eye.

Beta Alanine (BALA), unlike alpha-alanine, it is not involved in the synthesis of proteins in the body. This amino acid is part of carnosine, which, as a buffer system, prevents the accumulation of acids in the muscles during physical activity, decreases muscle pain after training, accelerates the recovery process after injuries.

Histidine (HIS) - an essential amino acid, which is a precursor of histamine, is a part of the active centers of many enzymes, is contained in hemoglobin, promotes tissue regeneration. In a rare genetic defect in histidase, histidinemia occurs, which can present with hyperactivity, developmental delay, learning difficulties, and in some cases, mental retardation.

Threonine (THRE) - an essential amino acid required for protein synthesis and the formation of other amino acids.

1-methylhistidine (1MHIS) is anserine derivative. The concentration of 1-methylhistidine in the blood and urine correlates with the consumption of meat food and increases with a deficiency. An increase in the level of this metabolite occurs with a deficiency of carosinase in the blood and is observed in Parkinson's disease, multiple sclerosis.

3-methylhistidine (3MHIS) is a product of actin and myosin metabolism and reflects the level of protein breakdown in muscle tissue.

Proline (PRO) synthesized in the body from glutamate. Hyperprolinemia due to a genetic defect in enzymes or against the background of inadequate nutrition, high content lactic acid in the blood, liver disease can lead to seizures, mental fatigue and other neurological pathology.

Lysine (LYS) - an essential amino acid, which is involved in the formation of collagen and tissue repair, the function of the immune system, the synthesis of proteins, enzymes and hormones. Lack of glycine in the body leads to asthenia, memory loss and impaired reproductive functions.

Alpha Aminoadipic Acid (AAA) - an intermediate product of lysine metabolism.

Cysteine \u200b\u200b(CYS) is an essential amino acid for children, the elderly and people with malabsorption nutrients... Have healthy people this amino acid is synthesized from methionine. Cysteine \u200b\u200bis part of the keratins of hair and nails, participates in the formation of collagen, is an antioxidant, a precursor of glutathione and protects the liver from the damaging effects of alcohol metabolites. Cystine is a dimeric cysteine \u200b\u200bmolecule. With a genetic defect in the transport of cystine in the renal tubules and intestinal walls, cystinuria occurs, which leads to the formation of stones in the kidneys, ureters and bladder.

Cystathionine (CYST) - an intermediate product of the metabolism of cysteine \u200b\u200bduring its synthesis from homocysteine. With hereditary deficiency of the enzyme cystathionase or acquired hypovitaminosis B 6, the level of cystathionine in the blood and urine increases. This condition is described as cystathioninuria, which is benign without obvious pathological signs, but in rare cases it can manifest itself as a deficit of intelligence.

Cysteic acid (CYSA) formed during the oxidation of cysteine \u200b\u200band is a precursor of taurine.

Taurine (TAU) is synthesized from cysteine \u200b\u200band, unlike amino acids, is a sulfonic acid containing a sulfo group instead of a carboxyl group. Taurine is a part of bile, participates in the emulsification of fats, is an inhibitory neurotransmitter, improves reparative and energy processes, has cardiotonic and hypotensive properties.

In sports nutrition, amino acids and proteins are widely used and are used to increase muscle mass... In vegetarians, due to the lack of animal protein in the diet, a deficiency of some essential amino acids... This study makes it possible to assess the adequacy of these types of nutrition and, if necessary, carry out their correction.

What is research used for?

  • Diagnostics of hereditary and acquired diseases associated with metabolic disorders of amino acids;
  • differential diagnosis of the causes of violations of nitrogen metabolism, removal of ammonia from the body;
  • monitoring compliance with diet therapy and the effectiveness of treatment;
  • nutritional status assessment and nutritional modification.

When is the study scheduled?

  • If there is a suspicion of a violation of the metabolism of amino acids in children, including newborns (vomiting, diarrhea, metabolic acidosis, a special smell and color of diapers, impaired mental development);
  • with hyperammonemia (an increase in the level of ammonia in the blood);
  • with a burdened family history, the presence of congenital aminoacidopathies in relatives;
  • when monitoring compliance with dietary recommendations, the effectiveness of treatment;
  • when examining athletes (for example, bodybuilders) using sports nutrition (proteins and amino acids);
  • when examining vegetarians.

What do the results mean?

  • Alanine (ALA):
  • Arginine (ARG):
  • Aspartic Acid (ASP):
  • Citrulline (CIT):
  • Glutamic Acid (GLU):
  • Glycine (GLY)
  • Methionine (MET)
  • Ornithine (ORN)
  • Phenylalanine (PHE)
  • Tyrosine (TYR)
  • Valine (VAL)
  • Leucine (LEU)
  • Isoleucine (ILEU)
  • Hydroxyproline (HPRO)
  • Serine (SER)
  • Asparagine (ASN)
  • Alpha-aminoadipic acid (AAA)
  • Glutamine (GLN)
  • Beta-alanine (BALA): 0 - 5 μmol / L.
  • Taurine (TAU)
  • Histidine (HIS)
  • Threonine (THRE)
  • 1-methylhistidine (1MHIS)
  • 3-methylhistidine (3MHIS)
  • Gamma-aminobutyric acid (GABA)
  • Beta-aminoisobutyric acid (BAIBA)
  • Alpha-aminobutyric acid (AABA): 0 - 40 μmol / l.
  • Proline (PRO)
  • Cystathionine (CYST): 0 - 0.3 μmol / L.
  • Lysine (LYS)
  • Cystine (CYS)
  • Cysteic acid (CYSA): 0.

Interpretation of the results is carried out taking into account age, dietary habits, clinical condition and other laboratory data.

An increase in the total level of amino acids in the blood is possible with:

  • eclampsia;
  • violation of fructose tolerance;
  • diabetic ketoacidosis;
  • renal failure;
  • reye's syndrome.

A decrease in the total level of amino acids in the blood can occur when:

  • hyperfunction of the adrenal cortex;
  • fever;
  • hartnup's disease;
  • chorea of \u200b\u200bHuntington;
  • inadequate nutrition, fasting (kwashiorkore);
  • malabsorption syndrome in severe diseases of the gastrointestinal tract;
  • hypovitaminosis;
  • nephrotic syndrome;
  • fever pappatachi (mosquito, phlebotomy);
  • rheumatoid arthritis.

Primary aminoacidopathies

Enhancement arginine, glutamine- arginase deficiency.

Enhancement arginine succinate, glutamine- arginosuccinase deficiency.

Enhancement citrulline, glutamine - citrullinemia.

Enhancement cystine, ornithine, lysine - cystinuria.

Enhancement valine, leucine, isoleucine - maple syrup disease (leucinosis).

Enhancement phenylalanine - phenylketonuria.

Enhancement tyrosine - tyrosinemia.

Secondary aminoacidopathies

Enhancement glutamine - hyperammonemia.

Enhancement alanine - lactic acidosis (lactic acidosis).

Enhancement glycine - organic aciduria.

Enhancement tyrosine - transient tyrosinemia in newborns.

Literature

  • Part 8. Amino Acids. In: Scriver CR, Beaudet AL, Valle D, Sly WS, Childs B, Kinzler KW, Vogelstein B, eds. The Metabolic and Molecular Bases of Inherited Disease... 8th ed. New York, NY: McGraw-Hill, Inc; 2001; 1665-2105.
  • Part IV. Disorders of amino acid metabolism and transport. Fernandes J, Saudubray J-M, Van den Berghe G, eds. Inborn Metabolic Diseases Diagnosis and Treatment... 3 rd ed. New York, NY: Springer; 2000; 169-273.
  • Part 2. Disorders of amino acid metabolism. Nyhan WL, Barshop BA, Ozand PT, eds. Atlas of Metabolic Diseases... 2nd ed. New York, NY: Oxford University Press Inc; 2005; 109-189.
  • Blau N, Duran M, Blaskovics ME, Gibson KM, eds. Physician's Guide to the Laboratory Diagnosis of Metabolic Diseases... 2nd ed. New York, NY: Springer; 2003.
  • Human Metabolome Database. Access mode: http://www.hmdb.ca/
Have questions?

Report a typo

Text to be sent to our editors:

Send message