Spectrum of Lysosomal Storage Disorders at a Medical Genetics Center in Northern India.

Background: There is limited literature available on the phenotypic and mutation spectrum of Indian patients with Lysosomal storage disorders (LSD). Objective: To elucidate the clinical, biochemical and mutation spectrum and to study the management options in Indian patients with lysosomal storage disorders. Design: Descriptive study. Subjects and Methods: All patients with lysosomal storage disorders diagnosed in the Medical Genetics department of a tertiary care institute in North India over a three year period from January 2008 to December 2010. Results: Out of the total of 93 patients clinically suspected to have LSDs, 68 (mean age at presentation 4.5 years) were confirmed to have LSDs based on the laboratory/neuroimaging findings and documentation of deficient enzymatic activity in the peripheral blood (leucocytes or plasma) and/or skin fibroblasts. The commonest clinical features at presentation were growth retardation (failure to thrive 47.2% and short stature 17.6%), hepatosplenomegaly (41.2%) and neuroregression (33.8%). A history of consanguinity was present in 32.4% of the families. Prenatal diagnosis was done in a total of 6 affected families; two pregnancies were found to be affected (one each with Gaucher disease and Tay Sachs disease) and in both cases the parents opted for termination of pregnancy. Of the remaining four pregnancies which were found to be unaffected and therefore continued, three were confirmed to be normal on post-natal follow up. Enzyme replacement therapy (ERT) is being given for a total of 8 LSD patients and all of them are showing a gradual amelioration of their symptoms and an improvement in the quality of life. Conclusions: Lysosomal storage disorders constitute an important group of genetic metabolic disorders for many of which therapeutic options are now available.

Utility of MLPA in mutation analysis and carrier detection for Duchenne muscular dystrophy.

CONTEXT: Multiplex ligation probe amplification (MLPA) is a new technique to identify deletions and duplications and can evaluate all 79 exons in dystrophin gene in patients with Duchenne muscular dystrophy (DMD). Being semi-quantitative, MLPA is also effective in detecting duplications and carrier testing of females; both of which cannot be done using multiplex PCR. It has found applications in diagnostics of many genetic disorders. AIM: To study the utility of MLPA in diagnosis and carrier detection for DMD. MATERIALS AND METHODS: Mutation analysis and carrier detection was done by multiplex PCR and MLPA and the results were compared. RESULTS AND CONCLUSIONS: We present data showing utility of MLPA in identifying mutations in cases with DMD/BMD. In the present study using MLPA, we identified mutations in additional 5.6% cases of DMD in whom multiplex PCR was not able to detect intragenic deletions. In addition, MLPA also correctly confirmed carrier status of two obligate carriers and revealed carrier status in 6 of 8 mothers of sporadic cases.