Clinical, pathological, and biochemical studies on an infantile case of sulfatide/GM1 activator protein deficiency.
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 GM1 ganglioside and a clear elevation in GM2 and GM3 gangliosides. Cultured skin fibroblasts had a normal activity for a large number of lysosomal enzymes including arylsulfatase A and galactocerebrosidase. When the cells were loaded with [14C]sulfatide only about 12% of the sulfatide was metabolized after 3 days. Extracts of the cells were subjected to SDS-PAGE and immunoblotting with antisphingolipid activator protein-1 (SAP-1) rabbit antiserum, and no cross-reacting material was detected confirming the diagnosis of metachromatic leukodystrophy caused by SAP-1 deficiency. This patient was clinically more severe than the other patients described previously with this deficiency. Further studies are underway to define the nature of the mutation in this patient.
Wenger
D A
DA
Department of Medicine, Jefferson Institute of Molecular Medicine, Jefferson Medical College, Philadelphia, PA 19107.
DeGala
G
G
Williams
C
C
Taylor
H A
HA
Stevenson
R E
RE
Pruitt
J R
JR
Miller
J
J
Garen
P D
PD
Balentine
J D
JD
D001344:Autopsy; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002675:Child, Preschool; D002855:Chromatography, Thin Layer; D046508:Culture Techniques; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000172:deficiency*; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000201:enzymology* / Q000473:pathology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D049231:Saposins; D049128:Sphingolipid Activator Proteins
D006023:Glycoproteins; C483345:PSAP protein, human; D049231:Saposins; D049128:Sphingolipid Activator Proteins