Shapiro et al. (1979) and Hahn et al. (1982) described 3 patients from 2 families with metachromatic leukodystrophy and normal arylsulfatase A activity.
Stevens et al. (1981) defined this biochemically distinct form of metachromatic leukodystrophy in ... Shapiro et al. (1979) and Hahn et al. (1982) described 3 patients from 2 families with metachromatic leukodystrophy and normal arylsulfatase A activity. Stevens et al. (1981) defined this biochemically distinct form of metachromatic leukodystrophy in 2 sibs of consanguineous Mexican-American parents. The clinical picture was that of juvenile MLD. Instead of the expected profound deficiency of arylsulfatase A, their enzyme levels were about half-normal, and the enzyme from fibroblasts had properties identical to those of normal fibroblasts. Nevertheless, hydrolysis of cerebroside sulfate by growing fibroblasts was markedly attenuated. Supplementation of the fibroblasts with the cerebroside sulfatase activator saposin B normalized the response in the loading test. The cerebroside sulfatase activator was purified and characterized as a heat stable, low molecular weight, anionic, lysosomal protein that exerts its effects by interacting with and dispersing the hydrophobic sulfatide (Fischer and Jatzkewitz, 1977). A bile salt such as sodium taurodeoxycholate or sodium cholate could substitute for the activator, indicating its essentially detergent mechanism of action. With a monoclonal antibody, Inui et al. (1983) demonstrated little or no CRM for the activator protein. They also demonstrated that sulfatide metabolism in cultured cells from the patient of Shapiro et al. (1979) could be corrected not only by the sulfatide sulfatase activator protein but also by the activator protein for GM1 ganglioside beta-galactosidase, indicating possible identity of these proteins. Wenger et al. (1989) described a fourth case of saposin B deficiency. The infant, who was unusually severely affected, was born of Nigerian parents. Rafi et al. (1992) demonstrated that cultured cells deficient in SAPB had correction of sulfatide metabolism when transfected with a virally transferred prosaposin cDNA; the cells produced normal levels of mature SAPB. Henseler et al. (1996) reported a Turkish boy, born of consanguineous parents, with juvenile metachromatic leukodystrophy. He acquired the ability to walk autonomously at age 14 months, but later developed motor difficulties and ceased walking at age 24 months. Clinical examination at age 25 months showed signs of peripheral neuropathy and slight psychologic delay. Laboratory studies showed normal arylsulfatase A activity with increased urinary excretion of sulfatides and globotriaosylceramide. Cultured fibroblasts of the patient metabolized very little endocytosed-labeled sulfatide in a sulfatide-loading experiment; normal catabolism was restored when mature saposin B was added to the culture medium. Wrobe et al. (2000) reported a 4-year-old girl of Spanish ancestry with saposin B deficiency. At the age of 2 years, she showed severe motor deterioration, hypotonia, weakness, and signs of CNS demyelination and polyneuropathy. At 4 years of age, nerve conduction was severely decreased, and sural nerve biopsy showed active demyelination and metachromatic deposits in macrophages. A bone marrow transplant (BMT) was attempted at the age of 4 years 9 months, but the child died 2 months postengraftment. Her younger sister, aged 2 years, also showed moderate hypotonia, patellar hyperreflexia, and signs of initial occipital demyelination, and BMT was performed at the age of 2 years 8 months. Kuchar et al. (2009) reported a boy with saposin B deficiency. He presented at age 9 months with signs of a mild, right-sided spastic hemiparesis. By age 2 years, he lost the previously acquired ability to walk a few steps, and showed decreased muscle strength with hyporeflexia. At age 43 months, he developed seizures, lost speech, and had spastic tetraparesis with almost no use of his hands. There was a progressive deterioration, and he was severely disabled at age 6 years with unreactive pupils. Brain MRI showed extensive white matter lesions and evidence of an old infarction. Urine analysis showed increased levels of sulfatide, similar to those seen in metachromatic leukodystrophy. Genetic analysis identified compound heterozygosity for 2 mutations in the PSAP gene (176801.0014 and 176801.0015), resulting in complete loss of 1 allele and generation of transcripts with deletions affecting only the SapB domain from the other allele.
In a Turkish boy with metachromatic leukodystrophy due to saposin B deficiency, Henseler et al. (1996) identified a homozygous mutation in the PSAP gene (176801.0006).
In a 4-year-old girl of Spanish ancestry with saposin B deficiency, ... In a Turkish boy with metachromatic leukodystrophy due to saposin B deficiency, Henseler et al. (1996) identified a homozygous mutation in the PSAP gene (176801.0006). In a 4-year-old girl of Spanish ancestry with saposin B deficiency, Wrobe et al. (2000) identified a mutation in the PSAP gene (176801.0007).