The utility of two dimensional electrophoresis in diagnosis of mucopolysaccharidosis disorders.

BACKGROUND: Mucopolysaccharidoses are a group of inherited lysosomal storage disorders consisting of 7 distinct clinical types and numerous subtypes. These are the result of deficiency of certain lysosomal degradative enzymes which are required to breakdown Glycosaminoglycans. The clinical features observed among Mucopolysaccharidoses subtypes show overlapping signs and symptoms with other lysosomal storage disorders and rheumatologic disorders. This makes clinical diagnosis a challenge. With the advent of new therapies, appropriate medical management is possible and hence establishing timely diagnosis has become crucial. METHODS: In this retrospective data analysis, 2 different diagnostic approaches were discussed. The first diagnostic approach involves screening by Glycosaminoglycans' quantification and two-dimensional cellulose acetate electrophoresis and confirmation by enzyme analysis. The second diagnostic approach involves direct enzyme analysis on basis of the clinical suspicion. RESULTS: This first approach seems to be appropriate for the diagnosis of almost all types of Mucopolysaccharidoses. The second approach is found to be more pertinent for type III Mucopolysaccharidosis. CONCLUSIONS: Our retrospective data analysis suggests that urinary Glycosaminoglycans screening followed by enzyme analysis confirmation seems to be rapid and cost effective approach for diagnosing these disorders.

Clinical evaluation of chitotriosidase enzyme activity in Gaucher and Niemann Pick A/B diseases: A retrospective study from India.

Plasma chitotriosidase originates from activated macrophages and is reported to be elevated in many Lysosomal Storage Disorders. Measurement of this enzyme activity has been an available tool for monitoring therapy of Gaucher disease. The degree of elevation of chitotriosidase is useful for differential diagnosis of Gaucher disease and Niemann Pick A/B. However the potential utility of this chitotriosidase assay depends on the frequency of deficient chitotriosidase activity in a particular population. We therefore aim to study the clinical utility of this assay Gaucher and Niemann Pick A/B diseases in the backdrop of chitotriosidase deficiency in our population. The study comprises 173 patients with clinical suspicion of either Gaucher disease (n=108) or Niemann Pick A/B (n=65) and 92 healthy controls. The plasma samples of controls, Gaucher disease, and Niemann Pick A/B showed chitotriosidase deficiency of 12%, 25% and 27% respectively. The degree of elevation of chitotriosidase in Gaucher disease and Niemann Pick A/B patients is 40-326 (11,325.7±6395.4nmol/h/ml) and 7-22 folds (1192.5±463.0nmol/h/ml) respectively. In view of these findings of distinguishable fold elevation of chitotriosidase in Gaucher disease or Niemann Pick A/B, it can be a potential surrogate differential diagnostic marker for these groups of diseases, except in the patients in whom this enzyme is deficient.

The relative frequency of lysosomal storage disorders: a medical genetics referral laboratory's experience from India.

Lysosomal storage disorders are a group of rare, genetically inherited metabolic disorders. Because the literature on epidemiologic data is scanty from India, we attempted to determine their relative frequency and regional distribution. Our retrospective study included 1558 patients with clinical suspicion of various lysosomal storage disorders referred to Sandor Lifesciences Pvt Ltd during 2007 to 2012. About 30% of the cases were tested positive, with sphingolipidoses as the most common subgroup, followed by mucopolysaccharidoses, and Gaucher disease as the most frequently occurring individual lysosomal storage disorder. Our data indicates that lysosomal storage disorders are more common in males than females and infants comprise the most common age group followed by juvenile. The burden of these disorders is predicted to be high in India because of the large population, coupled with the practice of consanguineous marriages. This study emphasizes the importance of epidemiologic studies in order to implement appropriate preventive measures.