Diagnostic methods for Lysosomal Storage Disease.

Lysosomal storage disorders (LSD) are a class of metabolic disturbance in which manifested by the accumulation of large molecules (complex lipids, glycoproteins, glycosaminoglycans, etc.) in lysosomes. LSDs have a wide range of clinical symptoms that may contain organ dysfunction, neurological and skeletal disorders. The first stage of diagnosis is clinically suspected by a physician. Next stage is enzyme activity assays including Fluorometry and MS/MS methods. These methods usually placed in newborn program screening. The second laboratory diagnostic stage is molecular examination (RFLP-PCR and ARMS-PCR, Mutations Scanning Methods, DNA sequencing, MLPA and NGS methods) that is confirmation of the enzyme assays. In this article, routine diagnostic methods for LSDs were discussed. The gold standard for enzyme activity assay and molecular diagnosis is TMS and NGS, respectively.

Frequency of Inborn Errors of Metabolism in a Northeastern Iranian Sample with High Consanguinity Rates.

OBJECTIVE: Inborn errors of metabolism (IEMs) are disorders with various manifestations that occur mainly in the pediatric population. In countries where consanguineous marriage is common, the association between consanguinity and IEMs is highly important. No studies have been conducted in Iran examining the impact of consanguinity on IEMs. METHODS: In this retrospective study, the incidences of metabolic disorders were evaluated for the years 2006 through 2016 in the North East Iran Regional Diagnostic Laboratory (Pardis Clinical and Genetic Laboratory). A total of 13,327 infants with clinical symptoms were referred and investigated for IEMs. Newborn screening was performed on samples from all patients suspected of having IEMs. RESULTS: Of 13,327 infants examined, 60 different IEMs were diagnosed in 1,118. The most frequent disorders among our patients were glucose-6-phosphate dehydrogenase deficiency (G6PDD) (14.04%), methylmalonic and propionic acidurias (MMA/PA) (9.12%), phenylketonuria (PKU) (8%), and isovaleric acidemia (IVA) (6.98%). A significant difference was found in the prevalence of amino acid disorders between the offspring of consanguineous and those of non-consanguineous parents. No statistically significant differences were found between the 2 groups for organic or fatty acids, carnitine or urine cycles, or lysosomal storage disorders. A total of 707 of the 1,118 infants with metabolic diseases (63.24%) were children of consanguineous parents. These findings show that consanguinity can be an important factor in the inheritance of recessive mutations in a homozygous state. CONCLUSION: This study found a greater frequency of metabolic diseases in offspring of consanguineous parents than in those of non-consanguineous parents in a population with a high rate of consanguinity.