Objective: Sandhoff disease (SD) is a rare neurological disease with high clinical heterogeneity. SD in juvenile form is much rarer and it is often misdiagnosed in clinics. Therein, it is necessary to provide additional case information to the literature.

Background: SD is a rare autosomal recessive inheritance neurological disease, a GM2 gangliosidoses, caused by mutations in HXEB gene, leading to deficiency in HEXA, HEXA&B. Clinical presentations of SD vary greatly. In most scenarios, it attacks infants, and can also affect adolescents and adults. Due to low incidence of SD, it is difficult to make correct diagnosis in clinics and it is necessary to raise clinical awareness of SD.

Method: Neurological physical examinations were conducted, Furthermore, Brain magnetic resonance imaging (MRI), whole exome sequencing (WES) and blood tests for leukocytic total β-Hex (HEXA&B) and HEXA activities were ordered.

Results: A 14 years-old boy with eight years of walking difficulties, and was ever misdiagnosed as spinocerebellar ataxia. His brain MRI showed marked atrophy in bilateral cerebellar hemispheres and mild atrophy in cerebrum, similar to other juvenile SD cases. Leukocytic HEXA&B and HEXA actives of this patient were decreased by 92.4% and 21.7% compared to the low limit of normal ranges, which were 75.4-158.6nmol/mg/h and 54.5-140.3nmol/mg/min. Following genetic testing, we found this patient carrying rs201580118 and a novel gross deletion in HEXB (g.74012742_74052694del). This was the first gross deletion identified at the 3’end of HEXB, associated with juvenile onset SD from China.

Conclusion: This case expanded our knowledge about the genotype and phenotype correlations in SD. Comprehensive genetic testing is important for the diagnosis of unexplained ataxia.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-juvenile-onset-sandhoff-disease-case-caused-by-hemizygous-mutations-of-hexb/