metachromatic leukodystrophy due to saposin B deficiency

Metachromatic leukodystrophy due to saposin B deficiency is an inherited disorder that primarily affects the nervous system and peripheral nerves. The condition is caused by changes in the PSAP gene, which plays a critical role in the activation of enzymes involved in lipid metabolism. Although precise prevalence estimates are not available, this autosomal recessive disorder typically presents in early childhood. Both motor function and cognitive development are impacted, with affected individuals often experiencing significant neurological and developmental challenges.

The clinical presentation of metachromatic leukodystrophy due to saposin B deficiency is marked by a range of neurological and motor impairments. Early in life, children may develop hypotonia, muscle weakness, and signs of peripheral neuropathy. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills. As the condition progresses, individuals commonly exhibit polyneuropathy, decreased nerve conduction velocity, and loss of ambulation, in addition to global developmental delay affecting cognitive functions. Not all individuals experience all features, and severity varies considerably.

Metachromatic leukodystrophy due to saposin B deficiency results from pathogenic variants in the PSAP gene. The PSAP gene is responsible for producing saposin proteins that are essential for the proper functioning of cerebroside sulfatase, an enzyme involved in the breakdown of certain fats in the body. The disruption of this process leads to an accumulation of sulfatides in the nervous system. Inherited in an autosomal recessive manner, the condition requires that an affected individual inherit two altered copies of the gene, one from each parent. Genetic counseling is recommended for families to understand recurrence risks and family planning options.

Currently, management focuses on supportive care and symptom management. Since there are no FDA-approved treatments or foundational therapies specifically linked to metachromatic leukodystrophy due to saposin B deficiency, treatment is tailored to address the individual’s needs through a multidisciplinary approach. Supportive therapies may include physical and occupational therapy to help maintain mobility and function, along with interventions to manage feeding difficulties and other complications. Genetic counseling is recommended, and patients should discuss treatment options with their healthcare team to determine which interventions may be appropriate for their specific situation.

The long-term outlook for individuals with metachromatic leukodystrophy due to saposin B deficiency is variable. This lifelong neurodevelopmental condition is characterized by an initial phase of developmental regression, followed by a period of relative stabilization and, in some individuals, later motor decline. With current standards of care, many individuals experience improvements in quality of life as supportive therapies and multidisciplinary management strategies evolve. Outcomes vary depending on symptom severity, age at diagnosis, and access to specialized care. Families are encouraged to connect with genetic counselors and support groups to help navigate the challenges associated with the condition.