# Juvenile Metachromatic Leukodystrophy in a Seven-Year-Old Child With a Familial History: A Case Report Suggesting Saposin B Deficiency

## TL;DR

A 7-year-old boy with a rare neurological disorder showed symptoms of MLD despite normal enzyme levels, highlighting the need for genetic testing.

## Contribution

This case suggests a possible atypical form of MLD linked to a PSAP gene variant and normal enzymatic activity.

## Key findings

- The patient had elevated urinary sulfatide levels with normal enzyme activity, indicating a non-classical MLD presentation.
- Genetic analysis identified a homozygous PSAP c.777G>A variant, pointing to saposin B deficiency.
- Comprehensive testing, including neuroimaging and electrophysiology, confirmed a leukodystrophic process and peripheral demyelination.

## Abstract

Metachromatic leukodystrophy (MLD) is a rare inherited disorder of the white matter with higher incidences in consanguineous populations. In children, manifestations vary with age of onset: early forms present with motor regression and developmental delay, whereas later forms begin with motor difficulties followed by behavioural or cognitive decline. We describe a 7-year-old boy with previously normal development who exhibited progressive motor deficits, speech difficulties, cognitive impairment, and loss of bladder control. Neurological examination revealed generalized hypotonia, areflexia, gait ataxia, and axial spasticity. Audiovisual function was preserved. Laboratory workup showed elevated urinary sulfatide levels despite normal enzymatic activity of the main sulfatide-degrading enzyme. Additional metabolic tests were unremarkable aside from signs of increased ketone bodies. Neuroimaging revealed white matter abnormalities consistent with a leukodystrophic process, and electrophysiological studies confirmed peripheral demyelination. Genetic analysis revealed a homozygous PSAP c.777G>A variant, affecting a gene essential for sulfatide degradation and suggesting a possible atypical form of MLD. This case highlights the diagnostic complexity of non-classical presentations and underscores the value of comprehensive metabolic and genetic evaluation. This case illustrates that MLD can present with normal enzymatic assays and highlights the importance of combined biochemical, neuroimaging, and genomic testing in children with rapid motor and cognitive decline.