Metachromatic leukodystrophy (MLD) is a rare autosomal recessive lysosomal storage disorder caused by the accumulation of sulfatides due to arylsulfatase A (ARSA) or saposin B deficiency. This accumulation results in progressive demyelination of the central and peripheral nervous systems, leading to neurological deterioration. MLD commonly presents in childhood, with clinical features varying by age of onset. Late- infantile forms often present with motor regression and developmental delay, while juvenile forms may initially manifest as behavioral or cognitive changes followed by motor decline. Diagnosis is based on clinical symptoms, brain MRI findings, elevated urinary sulfatides, enzymatic assays, and genetic testing. 

We report the case of a 7-year-and-5-month-old boy, born to consanguineous parents, with normal early development. He presented with progressive quadriparesis, gait imbalance, speech regression, incontinence, and cognitive decline. Neurological examination revealed generalized hypotonia, abolished deep tendon reflexes, ataxic gait, and mild spasticity of the upper trunk. Vision and hearing were preserved. Biological investigations showed elevated urinary sulfatides but normal ARSA enzyme activity. Plasma homocysteine and very long-chain fatty acids were normal. Amino acid chromatography revealed global hyperaminoacidemia, and organic acid analysis indicated increased ketone bodies without lactic acidosis. Brain MRI revealed bilateral symmetric white matter hyperintensities in the periventricular and subcortical regions, consistent with the “butterfly wing” sign typical of MLD. Electroneuromyography supported demyelinating polyneuropathy. While ARSA deficiency is the classical enzymatic defect in MLD, a normal ARSA level does not rule out the disease. In rare cases, the underlying cause is a mutation in the PSAP gene, which affects saposin B, a cofactor essential for sulfatide breakdown. This variant leads to the same pathological accumulation of sulfatides seen in classic MLD. The Whole-exome sequencing identified a homozygous variant of uncertain significance in the PSAP gene, suggesting saposin B deficiency. This case illustrates an atypical juvenile-onset MLD, likely linked to saposin B deficiency. 

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