Krabbe disease due to saposin A deficiency

Krabbe disease due to saposin A deficiency is a severe neurological condition marked by progressive deterioration of the central nervous system. It is caused by pathogenic variants in the PSAP gene and follows an autosomal recessive inheritance pattern. Affected individuals typically present in infancy with symptoms that affect multiple systems, and while precise prevalence estimates are not available, the condition is considered very rare. Modern care continues to evolve, offering hope for improved surveillance and management of complications.

The clinical presentation of this condition is dominated by significant neurological impairment and involves multiple obligate features. Nearly all affected individuals develop progressive neurologic deterioration, which is accompanied by abnormalities on brain imaging such as ventriculomegaly, global brain atrophy, and hyperintensity of the cerebral white matter. Other consistent findings include a mix of abnormal muscle tone with both hypertonia and atypical reflex patterns ( hyporeflexia and hyperreflexia), central apnea, tonic seizures, and peripheral axonal neuropathy. Affected children also experience feeding difficulties and respiratory challenges that may culminate in respiratory failure and a vegetative state. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills, although not all individuals experience the full spectrum of features and severity varies considerably.

This condition results from mutations in the PSAP gene, which plays a critical role in the metabolism of sphingolipids. The dysfunction of the protein product, saposin A, disrupts normal lipid degradation processes, leading to widespread neurological impairment. Inheritance is autosomal recessive, meaning that an affected individual inherits one mutated copy of the gene from each parent. Families should consider genetic counseling to understand the implications for future pregnancies and to receive guidance on family planning.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved or foundational treatments specifically available for this condition. Treatment is highly individualized and typically involves a multidisciplinary team that addresses the complex needs of affected individuals, including neurological, respiratory, and nutritional support. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Patients and families are encouraged to discuss available management options with their healthcare team and to seek genetic counseling as part of comprehensive care.

The overall course of Krabbe disease due to saposin A deficiency is highly variable. The condition is characterized by an initial phase of developmental regression, followed by a period of relative stabilization in some individuals and later potential motor or respiratory decline in others. Outcomes described in medical literature continue to evolve as standards of care improve, and many factors such as symptom severity, age at diagnosis, and access to specialized care influence long-term health. Families often find it helpful to connect with specialists familiar with this complex condition as well as genetic counselors for further guidance on managing expectations and planning for the future.