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.
Department of Medicine, Jefferson Institute of Molecular Medicine, Jefferson Medical College, Philadelphia, PA 19107.
D A
DA
Wenger
G
G
DeGala
C
C
Williams
H A
HA
Taylor
R E
RE
Stevenson
J R
JR
Pruitt
J
J
Miller
P D
PD
Garen
J D
JD
Balentine
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