Abstract
Introduction
Saposin B deficiency is an ultrarare lysosomal disorder caused by biallelic mutations in the PSAP gene. Although it clinically resembles classical arylsulfatase A (ARSA)–deficient metachromatic leukodystrophy (MLD), ARSA activity remains biochemically normal. Fewer than 30 genetically confirmed patients have been reported to date.
Patient Presentation
We describe 2 pediatric patients with homozygous PSAP gene mutations. Both presented with progressive neurodegeneration, spastic quadriparesis, demyelinating peripheral neuropathy, and radiologic findings consistent with MLD. The first patient harbored a canonical splice-site variant (c.577-1G>T), whereas the second carried a recurrent missense mutation (p.Cys241Ser). Notably, the first patient also had a PMP22 duplication consistent with coexisting CMT1A. Despite preserved ARSA activity, both patients fulfilled clinical and imaging criteria for MLD. Abdominal imaging revealed gallbladder sludge in both patients, with additional biliary tract dilation in one. These hepatobiliary findings have not been previously reported in genetically confirmed saposin B deficiency, broadening the known phenotypic spectrum.
Conclusion
These patients underscore the importance of PSAP gene sequencing in MLD-like presentations with normal ARSA activity and suggest that hepatobiliary involvement may be an underrecognized feature of saposin B–related MLD.
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