Combined SAP Deficiency (PSAP)

Pathogenic variants in the PSAP gene result in a spectrum of pan-ethnic, autosomal recessive neurological diseases, called metachromatic leukodystrophy, combined PSAP deficiency, atypical Gaucher disease, and atypical Krabbe disease. Metachromatic leukodystrophy results in progressive difficulty walking, deterioration of intelligence, and neuropathy. Eventually, seizures, paralysis, and loss of senses result in an unresponsive state. Age of onset can range from infancy to adulthood; life expectancy depends on the age of onset, but can be as early as childhood for those with early onset disease. Combined PSAP deficiency is a neurologic disease characterized by changes in brain structures, seizures, and difficulty controlling movements, and is fatal in infancy. Atypical Gaucher disease can cause a variety of symptoms, including anemia, organ enlargement, bone deformities, or changes in brain structures. Age of onset can range from infancy to adulthood; life expectancy depends on the age of onset, but can be as early as childhood for those with early onset disease. Atypical Krabbe disease involves loss of developmental milestones, irritability, stiffness, and hypersensitivity to stimuli. Subsequently, patients will experience a rapid, severe loss of mental and physical capabilities, until they no longer respond to stimulation. Age of onset can range from infancy to adulthood; life expectancy depends on the age of onset, but can be as early as childhood for those with early onset disease. It may be possible to predict the phenotype that will develop in some patients, depending on the pathogenic PSAP variants identified. However, this may not be possible in all patients.

For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.