galactosylceramide beta-galactosidase deficiency

Krabbe Disease

Clinical Characteristics
Ocular Features: 

Subtle cherry red spots have been reported in one patient.  More than half (53%) have abnormal VEP response but the ERG is normal.  Optic atrophy with blindness is not uncommon but the full ocular phenotype remains unknown.  A 6-month-old male child had MRI T2 evidence of intracranial optic nerve hypertrophy which was attributed to an accumulation of globoid cells.

Systemic Features: 

There is considerable variation in the time of onset and rate of progression in Krabbe disease, even within families.  Patients with infantile disease may present with symptoms at about 6 months of life, while others are not diagnosed until late childhood or adolescence.  Some evidence of psychomotor retardation is often the first sign of disease with ataxia and limb spasticity soon following.  Irritability is an early sign.  Neurophysiologic studies often show abnormal nerve conduction and this has been documented even in newborns.  The disorder is one of progressive neurodegeneration of both central and peripheral nervous systems leading to weakness, seizures and loss of protective reflexes.  The MRI may reveal T2 hyperintensity in cerebral and cerebellar white matter, internal capsules and pyramidal tracts.  Infection and respiratory failure are responsible for most deaths.

The life-span of Infants with Krabbe disease is approximately one year while those with late-onset disease may not develop symptoms until almost any age and the clinical course is highly variable.


This is an autosomal recessive disorder secondary to mutations in the GALC gene (14q31) encoding the enzyme galactosylceramidase, important in the growth and maintenance of myelin.

One patient has been reported with ‘atypical’ Krabbe disease (611722) secondary to a homozygous mutation in the PSAP gene (10q22.1).  The infant had a deficiency of saposin A as well as decreased galactocerebrosidase activity in white blood cells

Autosomal recessive
Treatment Options: 

Normal blood galactocerebrosidase can be restored and CNS deterioration may be delayed or improved with transplantation of allogeneic hematopoietic stem cells or umbilical cord blood.   However, some patients have residual language deficits and mild to severe delays in motor function.  Results are better if treatment is commenced during infancy before development of symptoms.  These treatments are experimental and long range outcomes remain uncertain.

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