Krabbe disease

Krabbe disease
Synonyms	Globoid cell leukodystrophy Galactosylceramide lipidosis GALC deficiency Galactocerebrosidase deficiency
Pronounce	N/A
Field	N/A
Symptoms	Infancy: Developmental delay, irritability, spasticity, hypotonia, microcephaly, optic atrophy Juvenile: Muscle weakness, vision loss, developmental regression Adult: Burning paresthesias in extremities, loss of manual dexterity, muscle weakness, sensory neuropathy, muscle atrophy
Complications	Severe neurological deterioration, paralysis, blindness, seizures, respiratory failure
Onset	Usually within 3 to 6 months of birth, but can present in childhood or adulthood
Duration	Progressive and degenerative
Types	Infantile, juvenile, and adult
Causes	Mutation of GALC gene
Risks	Parents who are heterozygous for a GALC mutation
Diagnosis	Histopathology, genetic testing, enzyme assay
Differential diagnosis	Metachromatic leukodystrophy, adrenoleukodystrophy, Pelizaeus-Merzbacher disease
Prevention	Prenatal diagnosis and screening of at-risk couples
Treatment	Primarily supportive care, symptomatic treatment, stem cell transplantation
Medication	No specific cure, palliative care is the mainstay
Prognosis	Poor in infantile onset; better outcomes with early hematopoietic stem cell transplantation
Frequency	Approximately 1 in 100,000 births
Deaths	High mortality rate, especially in early-onset forms

Krabbe disease (globoid cell leukodystrophy) is a rare, inherited lysosomal storage disorder affecting the central nervous system. It leads to progressive demyelination, causing severe neurological decline. The condition is caused by a mutation in the GALC gene, which results in a deficiency of the galactosylceramidase enzyme. This leads to the toxic accumulation of psychosine, damaging myelin-producing cells called oligodendrocytes.

The disease is named after Knud Krabbe, a Danish neurologist who first described the condition in 1916.

Signs and Symptoms

Symptoms vary based on the age of onset:

Krabbe Disease Symptoms by Age Group

Age of Onset	Symptoms
Infantile-onset (most common, before 12 months)	Irritability, hypotonia, spasticity, feeding difficulties, developmental regression, optic atrophy, seizures, paralysis, blindness
Juvenile-onset (1–10 years)	Muscle weakness, vision loss, behavioral changes, developmental regression, loss of motor skills, ataxia
Adult-onset (rare, after adolescence)	Burning paresthesias, muscle atrophy, sensory neuropathy, cognitive impairment, tremors, gait disturbances

Causes

Krabbe disease is caused by a mutation in the GALC gene, located on chromosome 14 (14q31). The condition is inherited in an autosomal recessive manner, meaning a child must inherit two copies of the mutated gene (one from each parent) to develop the disease.

The GALC enzyme deficiency leads to:

• Accumulation of galactosylceramide, leading to toxic effects on myelin-forming cells.
• Buildup of psychosine, which destroys oligodendrocytes, preventing proper myelin formation.
• Widespread demyelination, disrupting nerve signaling in the brain and spinal cord.

Diagnosis

Krabbe disease is diagnosed through:

• Newborn screening – Blood tests to measure GALC enzyme activity.
• Genetic testing – Identification of mutations in the GALC gene.
• MRI brain scan – Shows white matter abnormalities due to demyelination.
• Nerve conduction studies – Assess neurological impairment.
• Lumbar puncture (CSF analysis) – Elevated protein levels suggestive of leukodystrophy.
• Biopsy – Examining globoid cells in the nervous system.

Treatment

There is no cure for Krabbe disease. Treatment focuses on:

• Hematopoietic stem cell transplantation (HSCT) – If performed before symptoms appear, it may slow disease progression.
• Supportive care – Physical therapy, speech therapy, nutritional support.
• Seizure management – Anticonvulsants for epilepsy.
• Pain management – Muscle relaxants, analgesics.
• Feeding support – Gastrostomy tubes for feeding difficulties.
• Respiratory care – Assistance with breathing problems in advanced cases.

Prognosis

The prognosis depends on the age of onset:

• Infantile-onset – Severe and usually fatal by age 2.
• Juvenile-onset – Progresses more slowly, survival varies.
• Adult-onset – Milder but leads to progressive disability.

Epidemiology

Krabbe disease is rare, occurring in 1 in 100,000 births worldwide. However, its frequency varies by population:

• Higher rates in Scandinavian countries (1 in 50,000 births).
• Higher rates in the Druze population in Israel (6 in 1,000 births due to consanguinity).
• Extremely rare in Japan.

Society and Culture

The disease gained public attention through:

• Hunter Kelly, son of NFL quarterback Jim Kelly, who was diagnosed with Krabbe disease in 1997.
• Legislative efforts to include Krabbe disease in newborn screening programs in several U.S. states.

Krabbe Disease in Animals

Krabbe disease has been identified in:

• Dogs – Common in West Highland White Terriers and Cairn Terriers.
• Cats – Certain feline breeds.
• Monkeys and mice – Used for scientific research.

See Also

• Lysosomal storage diseases
• Leukodystrophy
• Genetic disorders
• Neurometabolic disorders
• Hematopoietic stem cell transplantation

External Links

Classification	ICD-10: E75.2 ICD-9-CM: 330.0 OMIM: 245200 DiseasesDB: 29468
External resources	MedlinePlus: 001198 eMedicine: ped/2892 Orphanet: 487

• GeneReviews entry on Krabbe disease
• OMIM entries on Krabbe disease

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