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It has an estimated prevalence of 1/100,000 in the Northern European population (higher in certain populations) and a worldwide incidence of 1/100,000-1/250,000 live births. The infantile form is the most common form and accounts for 85-90% of cases in the Northern European population. Later-onset forms may be more common in other populations.

The infantile form has an onset at 2-6 months of age and is divided into 3 stages. In the first stage, symptoms include irritability, stiffness, poor head control, feeding difficulties, intermittent thumb clasp, episodes of increased temperature, and developmental delay. In the second stage, hypertonic episodes occur with opisthotonus, myoclonic seizures, developmental regression, fisting and vision deficits. In the third stage, hypotonia, blindness and deafness occur. Patients progress into a vegetative state and usually die before the age of 2-3 years, generally due to respiratory infections. In the late infantile/juvenile (1-16 years) and adult (>16 years) forms, the presenting symptoms vary greatly and progression is variable (generally slower in older patients). Patients with late infantile /juvenile onset most resemble infantile patients, while the first signs in adult forms are often weakness, gait disturbances (spastic paraparesis or ataxia), burning paresthesias, hemiplegia, and/or vision loss, with or without peripheral neuropathy. Cognitive regression is variable and often absent in adult forms. In the later-onset forms the disease progresses at a slower rate than infantile patients with some adults living until the sixth decade with mild symptoms.

The disease is due to mutations in the GALC gene (14q31) encoding the lysosomal enzyme galactocerebrosidase (GALC), that catabolizes the hydrolysis of galactose from galactocerebroside and galactosylsphingosine (psychosine). The accumulation of cytotoxic psychosine leads to apoptosis of oligodendrocytes and demyelination of the CNS and PNS. Rarely, infantile Krabbe disease is caused by a mutation in the PSAP gene (10q21-q22), encoding prosaposin which is necessary for GALC activity.

Diagnosis is suspected by the clinical picture, slow nerve conduction velocity, abnormal electroencephalogram, and brain MRI revealing white matter abnormalities (demyelination, gliosis, late-stage cerebral atrophy, cerebral calcifications). It is established by enzymatic assays in leukocytes or cultured fibroblasts that reveal, in almost all cases, a deficiency of GALC activity. Biopsy of nervous tissues is not indicated for diagnosis. Mutation analysis is sometimes done to confirm the diagnosis. Newborn screening (NBS) may be available in certain regions; however additional studies are required after an initial positive test.

Differential diagnosis includes metachromatic leukodystrophy, GM1 gangliosidosis, GM2 gangliosidosis, Canavan disease, encephalopathy due to prosaposin deficiency, X-linked adrenoleukodystrophy, Pelizaeus-Merzbacher disease and Alexander disease.

Antenatal diagnosis (enzymatic assay or mutation analysis) is possible for at-risk families. If the disease-causing mutations in the family are known, pre-implantation genetic diagnosis is also possible.

Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% chance of having an affected child.

Treatment is currently limited to hematopoietic stem cell transplantation in pre-symptomatic infantile patients and mildly affected late-onset patients. It has been shown to slow the progression of the disease. Most individuals predicted to have infantile Krabbe disease and treated before 4 weeks of age can live into the second decade with mostly preserved cognitive functioning, but with difficulty in walking and in expressive language.

Steady neurodegeneration and early death within two to three years occur in most infantile cases. In late infantile/juvenile patients, the disease is generally fatal 2-7 years after the symptoms begin. Adult-onset patients can survive many years after symptoms present.