Introduction of Tandem Mass Spectrometry (MS/MS) Technology in the Program of Selective Screening of Hereditary Metabolic Diseases in Kazakhstan
Inborn errors of metabolism (IEM) are not have specific clinical signs, they masquerade as other diseases, and are difficult to diagnose using only clinical manifestations or routine laboratory tests. IEM most commonly manifest in early infancy and childhood. Despite the fact that most IEM are rare in the population, they occupy one of the first places in the structure of childhood pathology, early infant mortality and disability. IEM often remains undiagnosed, while timely diagnosis and timely treatment started can prevent severe systemic damage leading to death and disability. The appointment of a special treatment (diet therapy, cofactors, enzyme replacement therapy) prevents or significantly inhibits the development of the pathological process, especially if the diagnosis is made in the early stages of the disease. To start pathogenetic treatment as early as possible, it is necessary to diagnose IEM as accurately and as early as possible. Among the diseases included in mass screening programs IEM are especially important due to the development of disability and early mortality in the absence of timely diagnosis and treatment, as well as a high risk of recurrence in burdened families. In this connection, the main goals of mass screening - the prevention of disability in children and the reduction of early infant mortality - dictate the need to introduce modern technologies for preclinical diagnosis of IEM. Based on the results of the study, it is planned to scientifically substantiate the need for the introduction of selective screening of children for hereditary metabolic diseases using the technology of tandem mass spectrometry in the Republic of Kazakhstan for timely diagnosis, therapy of IEM and prevention of disability. The introduction of a selective newborn screening program for IEM should always be preceded by a study aimed at studying the prevalence of the disease in a certain region, determining regional reference values of the studied metabolites. Local incidence and outcome data can be used to persuade health officials to prioritize screening in health care spending. The main scientific question and hypothesis of the project is whether it is necessary to introduce tandem mass spectrometry technology in the neonatal screening program for IEM.
• Referense group: Healthy male and female children aged 1 day to 18 years. Newborns born during the study period (all newborns will be included in this study will meet all selected inclusion criteria to ensure that they do not suffer from any disorder or disease. Healthy male and female newborns must weigh within 2500 -4000 g, gestational age 37-42 weeks, Apgar score above 7 for 10 min.) Sample group: children aged 1 day to 18 years will be selected if one of the main criteria or two or more additional criteria (symptoms) is identified.
• Main criteria (symptoms): 1) Sudden deterioration in the clinical condition of the child after a period of normal development (days, weeks, months): acute metabolic encephalopathy, lethargy (coma), seizures resistant to antiepileptic therapy. 2) Hepatomegaly (hepatosplenomegaly). 3) Metabolic acidosis with an increase in the anion gap. 4) Multiple fractures. 5) Child mortality in the family from diseases with similar symptoms.
• Additional criteria (symptoms): Treatment-resistant seizures; Abnormal muscle tone: dystonia, hyperkinesis, hypotension; Speech delay; Mental retardation of unknown cause; Cardiomyopathy; Tachypnoea; Frequent spitting up (vomiting); Osteo-articular abnormalities (joint stiffness, chest deformity, rickets-like changes); Hernias (umbilical, inguinal-scrotal); Persistent or recurrent hypoglycemia; Metabolic alkalosis; Increase in ketone bodies in the blood and (or) urine; Hyperammonemia; Increase in the level of liver enzymes (AlAT, AST) more than 1.5 times the norm; Increase in the level of creatine phosphokinase (CPK) more than 2 times the norm; Decrease in the level of alkaline phosphatase (AP) below the age norm; Imaging or electrophysiological studies suggesting metabolic disorders; Leukopenia; Thrombocytopenia; Abnormal urine, body, ear wax, any unusual smell; Hair growth disorders, alopecia; Ophthalmological anomalies; Unusual appearance, dysmorphic features; History of previous sibling death of unknown cause; Parents' consanguinity; A positive family history of metabolic disorders.