Burden of Lysosomal Storage Disorders in India: Experience of 387 Affected Children from a Single Diagnostic Facility

Abstract

Lysosomal storage disorders (LSDs) are considered to be a rare metabolic disease for the national health forum, clinicians, and scientists. This study aimed to know the prevalence of different LSDs, their geographical variation, and burden on the society. It included 1,110 children from January 2002 to December 2012, having coarse facial features, hepatomegaly or hepatosplenomegaly, skeletal dysplasia, neuroregression, leukodystrophy, developmental delay, cerebral-cerebellar atrophy, and abnormal ophthalmic findings. All subjects were screened for I-cell disease, glycolipid storage disorders (NiemannPick disease A/B, Gaucher), and mucopolysaccharide disorders followed by confirmatory lysosomal enzymes study from leucocytes and/or fibroblasts. Niemann-Pick disease-C (NPC) was confirmed by fibroblasts study using filipin stain. Various storage disorders were detected in 387 children (34.8 %) with highest prevalence of glycolipid storage disorders in 48 %, followed by mucopolysaccharide disorders in 22 % and defective sulfatide degradation in 14 % of the children. Less common defects were glycogen degradation defect and protein degradation defect in 5 % each, lysosomal trafficking protein defect in 4 %, and transport defect in 3 % of the patients. This study demonstrates higher incidence of Gaucher disease (16 %) followed by GM2 gangliosidosis that includes Tay-Sachs disease (10 %) and Sandhoff disease (7.8 %) and mucopolysaccharide disorders among all LSDs. Nearly 30 % of the affected children were born to consanguineous parents and this was higher (72 %) in children with Batten disease. Our study also demonstrates two common mutations c.1277_1278insTATC in 14.28 % (4/28) and c.964G>T (p.D322Y) in 10.7 % (3/28) for Tay-Sachs disease in addition to the earlier reported c.1385A>T (p.E462V) mutation in 21.42 % (6/28).

Gaucher Disease

“…3,96 In our Indian multicentre study which included 5 centres from across the country, there was history of consanguinity in 50% of families. The first 25 patients who were treated with ERT were analyzed and found to have significant improvement in the liver and spleen sizes and blood counts.…”

“…3 The risk of developing GD increases with consanguinity in the family. Its frequency differs with different populations-being most prevalent-1:450 birth incidence in individuals of Ashkenazi Jewish descent.…”

Clinical genetics and India

“…[2] There lies a great need to study the epidemiology of these genetic disorders in Indian population. Most of these genetic disorders are "rare disorders" which are difficult to diagnose.…”

Amniotic fluid glycosaminoglycans in the prenatal diagnosis of mucopolysaccharidoses - A useful biomarker

“…The burden of lysosomal storage disorders in India is high as reported in a recent study of LSDs [3]. With the availability of diagnostic facilities, more number of LSDs were being identified across the world and there is an increased demand for prenatal diagnosis (PND).…”