ADULT SANDHOFFS-DISEASE - R505Q AND I207V SUBSTITUTIONS IN THE HEXB GENE OF THE FIRST JAPANESE CASE

We describe a 31-year-old Japanese man with adult Sandhoff's disease p resenting as spinocerebellar degeneration. There was a marked cerebell ar atrophy on MRI, and proliferation of abundant PAS-positive foamy ma crophages in the rectal mucosa. The activities of total beta-Hex, beta -Hex A, and beta-Hex B in leucocytes of the patient were 14%, 15%, and 6% of control values, respectively. However, oligosacchariduria or ul trastructural storage materials in liver tissue were nil. Direct seque ncing of cDNA and genomic DNA, and restriction digestion revealed two different homozygous base substitutions in the HEXB gene: the G(1514)- ->A substitution (R505Q) and the A(619)-->G substitution (I207V). The parents were consanguineous. His healthy mother, an enzymatic heterozy gous carrier, was homozygous for I207V but heterozygous for R505Q muta tion. Thus, the patient is probably homozygous for both base substitut ions and a R505Q mutation may be linked to the phenotype of adult Sand hoff's disease. (C) 1998 Elsevier Science B.V.