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Krabbe Disease

Crab
Picmonic
Krabbe’s disease is a sphingolipidosis caused by a deficiency of the enzyme galactocerebrosidase. This enzyme is required for the catabolism of galactocerebroside to ceramide and galactose and a deficiency of the enzyme causes accumulation of unmetabolized galactocerebroside which affects the growth and development of the myelin sheath around nerves. Infants with Krabbe’s disease are normal at birth but begin to show symptoms between the ages of 3 and 6 months with irritability, fevers, feeding difficulties, and developmental delay. Other symptoms include optic atrophy and peripheral neuropathy. The disease can be diagnosed by finding globoid cells, which are engorged macrophages with multiple nuclei in the parenchyma and around blood vessels. 
7 KEY FACTS
PATHOPHYSIOLOGY
Autosomal Recessive
Recessive-chocolate

Krabbe Disease is inherited in an autosomal recessive modality. This means two copies of the abnormal gene must be present in order for the disease to develop.

Galactocerebrosidase Deficiency
Galaxy-cerebro-guy-on-side

This enzyme is required for the catabolism of galactocerebroside to ceramide and galactose and a deficiency of the enzyme causes accumulation of unmetabolized galactocerebroside which affects the growth and development of the myelin sheath around nerves.

Increased Psychosine
Up-arrow Psycho-sun

Galactocerebrosidase normally breaks down psychosine, and a lack of the former leads to an increased buildup of psychosine. Increased psychosine levels are believed to lead to widespread destruction of oligodendroglia in the CNS and to subsequent demyelination, as psychosine preferentially accumulates in white matter.

SIGNS AND SYMPTOMS
Developmental Delay
Developmental-bus

Infants with Krabbe's disease are normal at birth but begin to show symptoms between the ages of 3 and 6 months with irritability, fevers, feeding difficulties, and developmental delay. The developmental delay is directly related to damage of the myelin sheaths caused by accumulation of galactocerebroside.

Peripheral Neuropathy
Purple-wavy Neuron-extremities

Peripheral neuropathy is a general term that describes damage to the nerves of the peripheral nervous system. Symptoms can include abnormal sensory function and motor symptoms. Peripheral neuropathy is a common finding in Krabbe's disease due to damage of the myelin sheaths in the peripheral nerves.

Optic Atrophy
Optic @-trophy glasses

Optic atrophy occurs when there is loss of some or most of the fibers in the optic nerve. Optic atrophy can lead to vision changes or vision loss and is a common finding in Krabbe's disease due to damage of myelin.

DIAGNOSIS
Globoid Cells
Globe

Globoid cells are engorged macrophages with multiple nuclei found in the parenchyma and around blood vessels in individuals with Krabbe's disease. Finding globoid cells can be diagnostic of Krabbe's disease.

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