OMIM ID:
Krabbe Disease
Alternate Names
Defective Genes
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.
Genetics
Inheritance
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
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.