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In a family with juvenile metachromatic leukodystrophy (sulfatide lipidosis) 2 patients showed residual arylsulfatase A activities of 5–6%. The patients' healthy father was characterized biochemically by a 39% normal activity of leukocyte plus plasma arylsulfatase A. The father was further characterized by a high sulfatide excretion (0.2–0.5 mg/l urine) and, paradoxically, by a normal sulfatide degrading enzyme activity in vitro. This special carrier is suspected to be heterozygous for a) arylsulfatase A deficiency and b) arylsulfatase A (sulfatidase) lability. This presumed additional genetic defect could be the cause of the sulfatide excretion which, in turn, would be a sign of the preclinical stage of an exceptional form of adult metachromatic leukodystrophy. The normal sulfatidase activity seems to be due to an in vitro effect.

Cultured skin fibroblasts from controls and patients with lysosomal storage diseases were loaded with GM1 ganglioside that had been labelled with tritium in its ceramide moiety. After a 65-h or 240-h incubation, a large percentage of this ganglioside remained undegraded in GM1 gangliosidoses, whereas in the other storage diseases studied, one of its metabolites accumulated by 2–4 fold relative to controls. Labelled GM2 ganglioside accumulated in 4 variants of GM2 gangliosidosis, whereas labelled GM3 ganglioside accumulated in sialidosis, galactosialidoses and sphingolipid activator protein 1 (SAP-1, saposin B) and prosaposin (saposin A, B, C an D) deficient lipidoses. The reduced degradation of GM3 ganglioside in the SAP-1 and prosaposin deficiencies was attributed to the deficient function of SAP-1. The prosaposin deficient cells also showed a reduced re-utilization of radioactive metabolites from GM1 ganglioside (i.e. sphingosine and fatty acid) for phospholipid biosynthesis compared with fibroblasts from the SAP-1 deficient patient or normal controls. This anomaly was ascribed to the previously shown defect in ceramide degradation in prosaposin deficiency.

The recessive inheritance of the enzyme deficiencies (total hexosaminidase, hexosaminidase A, arylsulfatase A) in nine families with neurolipidoses (variant 0 of Tay-Sachs disease=“Sandhoffs disease”, classic Tay-Sachs disease, metachromatic leukodystrophy) has been studied. 62 family members were identified as: genotypically normals, phenotypically normal heterozygous carriers, or patients, according to the enzyme levels (normal, about half normal or low) in the leukocytes. The activities of the lysosomal enzymes involved in the diseases are related to the mean relative activity of three or four lysosomal reference enzymes thereby identifying the heterozygous carrier state by the enzyme level about half the normal enzyme. It cannot be completely excluded that the heterozygous state or total enzyme deficiency occur more frequently than would be expected according to Mendel's laws. This problem is discussed.