Clinical presentation and outcome in infantile Sandhoff disease: a case series of 25 patients from Iranian neurometabolic bioregistry with five novel mutations

Ali Reza Tavasoli,
Nima Parvaneh,
Mahmoud Reza Ashrafi,
Zahra Rezaei,
Johannes Zschocke and
Parastoo RostamiEmail author

Orphanet Journal of Rare Diseases201813:130

https://doi.org/10.1186/s13023-018-0876-5

Received: 7 February 2018
Accepted: 18 July 2018
Published: 3 August 2018

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.