PRELIMINARY RESULTS ON THE USING TANDEM MASS SPECTROMETRY IN DIAGNOSIS OF INHERITED METABOLIC DISEASES

Abstract

BACKGROUND According to the results of the researches common indexes of the prevalence of inherited metabolic diseases (IMD) varies from 1 to 800 on 1 to 2500 alive newborns. IMD are taking one of the first places among children pathology, early children death (40%) and disability[1]. According to systematic review of the 43 forms of the inborn errors of metabolism are related to unexpected death of newborns. For IMD it is common to have a wide spectrum of the unusual clinical manifestation, often they are not diagnosed, while well timed diagnoses and proper treatment are able to prevent severe systematic lesions, which lead to death and disability[2]. For that reason one of the most significant problems of the modern pediatrics is to early diagnosis of IMD. The only way to diagnosis of orphan metabolic diseases is the tandem mass spectrometry (TMS) [3]. AIM Scientifically substantiate the need for implementation of selective screening IMD of children using TMS method in Republic of Kazakhstan (RK) for early diagnosis, therapy of the inherited metabolic diseases, to reduce disability and death rate. MATERIALS AND METHODS Material of the research – dry blood spots, taken using standard methodology on filtered DBS papers, which are used in RK in the program of neonatal screening (for retrospective research – archived samples of the dry blood spots of the children dead during first year of life). Method of the research is tandem mass spectometry (QSight Perkin Elmer). RESULTS Analysis of the archived dry blood spot samples showed metabolic deviations in 20.4% of the cases. The detected changes are related to amino acids metabolic disorders, defects of -oxidation of the fat acids, decrease activity of the glucocerebrosidase (Gaucher’s disease) and sphingomyelinase (Nimman – Pick disease). Results of the selective screening have shown metabolic disorders in 5% of the cases (defects of -oxidation of the fat acids, aminoacidopathy, organic aciduria). CONCLUSIONS The preliminary results of the using TMS for the diagnosis of IMD have shown the need for implementation of selective screening IMD using TMS, which is able to conduct diagnosis of 75 metabolites of 49 IMD in single blood spot, which were not detected in RK previously. Taking into the consideration economic expenses of the government, related to the costs of the systematic treatment, medical service, life expectancy and lifelong support of the disabled children with IMD, early detection of orphan metabolic diseases is the vital condition of the decrease of newborn and children death rate, sickness rate and disability. This research study was carried out as a part of a scientific project funded by West Kazakhstan Marat Ospanov Medical University.