Clinical, pathological, and biochemical studies on an infantile case of sulfatide/GM1 activator protein deficiency

Abstract

A 28‐month‐old black male died with severe complications of mental and motor deterioration, seizures, and aspiration. Autopsy demonstrated moderate liver enlargement, normal spleen and kidneys, small testes, and a grossly normal brain. Further examination showed irregular macrogyrae with evidence of a storage or sclerotic process. Thin layer chromatography of the lipids in formalin‐fixed tissue demonstrated elevated levels of ceramide trihexoside and possibly sulfatides in liver and a decrease in the ratio of galactosylceramide to sulfatide in brain. Examination of the gangliosides in formalin‐fixed brain indicated a slight increase in the percentage of G_M1 ganglioside and a clear elevation in G_M2 and G_M3 gangliosides. Cultured skin fibroblasts had a normal activity for a large number of lysosmal enzymes including arysulfatase A and galactocerebrosidase. When the cells were loaded with [¹⁴C]sulfatide only about 12% of sulfatide was metabolized after 3 days. Extracts of the cells were subjected to SDS‐PAGE and immunoblotting with antisphingolipid activator protein‐1 (SPA)rabbit antiserum, and no cross‐reacting material was detected confirming the diagnosis of metachromatic leukodystrophy caused by SAP‐1deficiency. This patient was clinically more severe than the other patuent described previsously with this deficiency. Further studies are underway to define the nature of the mutation in this patient.