Krabbe disease

Krabbe disease is a lysosomal disorder that primarily affects the white matter of both the central and peripheral nervous systems. It is caused by mutations in the GALC gene, which lead to reduced activity of the galactocerebrosidase enzyme. This condition can present in different forms, including infantile, late-infantile/juvenile, and adult variants, with many affected children initially developing typically before showing signs of regression. It is an uncommon condition, affecting approximately 1 to 9 per 100,000 people.

Individuals with Krabbe disease typically exhibit reduced tissue galactocerebrosidase activity and progressive spasticity, which are consistently observed in affected patients. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills. Other clinical features include axial hypotonia and, in some cases, CNS demyelination. Not all individuals experience all features, and severity varies considerably.

Krabbe disease is caused by pathogenic variants in the GALC gene, which encodes the enzyme galactocerebrosidase. The deficiency of this enzyme leads to the buildup of toxic substances that damage the myelin sheaths of nerve cells, disrupting normal nerve function. It is inherited in an autosomal recessive pattern, meaning an individual must inherit two mutated copies of the gene—one from each parent—to manifest the condition. Genetic counseling is recommended to help families understand recurrence risks and available testing options.

Currently, management of Krabbe disease focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically for this condition. Treatment is individualized and typically involves a multidisciplinary team to address neurological, physical, and developmental challenges. Patients are encouraged to discuss available management options with their healthcare team and to seek genetic counseling for further guidance.

Krabbe disease is a lifelong neurodevelopmental condition characterized by an initial regression, followed by a period of relative stabilization and, in some individuals, later motor decline. Outcomes vary depending on factors such as the severity of symptoms, age at diagnosis, and access to specialized care, and outcomes described in medical literature continue to evolve as standards of care improve. Not all individuals experience all features, and variability in the clinical course is common. Families are encouraged to connect with specialists and patient support groups, and genetic counseling can provide further guidance for managing long-term care.

Several clinical trials are currently investigating new treatment approaches for Krabbe disease. Individuals interested in clinical trials can search ClinicalTrials.gov or consult with their care team regarding eligibility.