Clinical Presentation and Molecular Findings in Two Index Patients with GM2 Gangliosidosis/Mb. Sandhoff

Background/Purpose: Sandhoff disease is an autosomal-recessive inherited lysosomal storage disorder and among the more frequent subtypes of sphingolipidoses (1:130,000). Mutations in the HEXB gene cause a combined β-hexosaminidase A and B deficiency with neuronal storage of GM2 gangliosides and oligosaccharides and pathological excretion of oligosaccharides. A cherry red spot is occasionally found. We present two unrelated patients with a late infantile and juvenile form, respectively.

Methods: Case report of two unrelated patients with Sandhoff disease.

Results: Patient 1 (P1) had primary motor developmental delay and presented at the age of 30 months with proximal and distal weakness, followed by progressive spastic paraplegia, loss of ambulation, and regression of speech. Patient 2 (P2) presented with stagnation of motor development, absent speech development, regression in social behavior, and epileptic seizures before 24 months. Cranial MRI revealed mild, unspecific signal alterations in the deep white matter and funduscopy showed a cherry red spot in both patients. Oligosaccharide excretion was pathologic in P1 and unremarkable in P2. Hexosaminidase A and B activity was 5% in P1 and 7% in P2. Results of genetic testing are pending.

Conclusion: P1 had a juvenile onset with pseudo-peripheral symptomatology. This phenotype has been reported in other late-onset forms of GM2 gangliosidoses. P2 showed a typical late infantile course, but a normal urinary profile of oligosaccharides. A cherry red spot should be searched in all patients with unclear motoneural affection or neurodegeneration. Even in the presence of normal urinary excretion of oligosaccharides, hexosaminidase A and B activities should be analyzed in leukocytes or fibroblasts.