Clinical presentation and outcome in infantile Sandhoff disease: a case series of 25 patients from Iranian neurometaboli
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RESEARCH
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Clinical presentation and outcome in infantile Sandhoff disease: a case series of 25 patients from Iranian neurometabolic bioregistry with five novel mutations Ali Reza Tavasoli1, Nima Parvaneh2, Mahmoud Reza Ashrafi1, Zahra Rezaei1, Johannes Zschocke3 and Parastoo Rostami4*
Abstract Background: Infantile Sandhoff disease (ISD) is a GM2 gangliosidosis that is classified as a lysosomal storage disorder. The most common symptoms of affected individuals at presentation are neurologic involvement. Here we report clinical course and demographic features in a case series of infantile Sandhoff disease. Enzymatically and some genetically proven cases of ISD were extracted from the Iranian Neurometabolic Registry (INMR) in Children’s Medical Center, Iran, Tehran from December 2010 to December 2016. Result: Twenty five cases of infantile SD (13 female, 12 male) were included in this study. The age range of patients was 9–24 months with a mean of 15.8 months. The consanguinity rate of parents affected families was about 80%. The mean age of patients at disease onset was 6.4 months and the mean age at diagnosis was 14 months. Patients were diagnosed with a mean delay of 7.8 months. Eleven of patients died due to aspiration pneumonia and intractable seizure. The most common features at presentation (92%) were developmental delay or regression in speech and cognitive domains. Cherry red spots were detected in 17 patients (68%). Organomegaly was detected only in two patients. Enzyme studies showed marked reductions of both Hexosaminidase A and B in all patients. HEXB gene mutation studies performed in eight patients identified 6 different mutations, which five of them were novel. Conclusion: Infantile SD should be considered for each child presented with neurologic symptoms such as developmental delay and regression and cherry red spots in ophthalmic examination. Organomegaly is not a frequent clinical finding in infantile SD. Additionally; there are a genetic heterogenisity among Iranian patients. Keywords: Infantile Sandhoff disease, Organomegaly, Cherry red spot, HEXB gene
Background Lysosomal storage disorders (LSDs) are a specific group of inborn errors of metabolism including more than fifthy different diseases caused by a structural defect or deficiency of lysosomal enzymes [1]. GM2 gangliosidosis is one group of LSDs that is classified into three types: Sandhoff (0 variant), Tay-Sachs (B variant) and GM2 activator deficiency (GM2A-AB variant). Mutations in HEXA, HEXB and GM2A genes that are inherited by * Correspondence: [email protected] 4 Growth and Development Research Center, Division of Endocrinology and metabolism, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran Full list of author information is available at the end of the article
autosomal recessive pattern lead to defective β-Hexosaminidase activity and accumulation of GM2 ganglioside in the intracellular organelles of visceral and neural cells [2]. Sandhoff disease (SD, OMIM 26880) due to a deficiency
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