A UNIQUE FAMILIAL LEUKODYSTROPHY WITH ADULT-ONSET DEMENTIA AND ABNORMAL GLYCOLIPID STORAGE - A NEW LYSOSOMAL DISEASE

Two adult siblings with early onset dementia are described. At present ation, in their early 30s, they showed poor judgment and disinhibition . A progressive dementia ensued over several years. Brain MRI disclose d diffusely increased T2 signal in the cerebral white matter, suggesti ve of a leukodystrophy. Numerous lysosomal enzyme assays including leu cocyte arylsulphatase A and galactocerebrosidase activities, plasma an d fibroblast very long chain fatty acid concentrations, and urinary su lphatide concentrations were normal, as were CSF analyses. A brain bio psy disclosed periodic acid Schiff (PAS) and Sudan black positive mate rial in perivascular macrophages which, by electron microscopy, consis ted of stacks of straight or curvilinear paired membranes within angul ate lysosomes, indicative of abnormal glycolipid accumulation. The com bination of clinical, radiological, biochemical, and pathological feat ures of this degenerative disease is not consistent with that of any o f the known leukodystrophies or lysosomal storage disorders. These fin dings suggest a previously undescribed familial glycolipid storage dis order causing an adult onset leukodystrophy and presenting with behavi oural symptoms that mimic a psychiatric disorder.