Galactosylcereamidase deficiency

Alternative names 
Globoid cell leukodystrophy; Galactosylcerebrosidase deficiency; Krabbe disease

Definition
Krabbe disease is an inherited disorder characterized by a deficiency of the enzyme galactocerebroside beta-galactosidase (galactosylcereamidase). It results in destruction of myelin, a fatty material that surrounds and insulates many of the nerves.

Causes, incidence, and risk factors

Krabbe disease is inherited as an autosomal recessive trait. It is most common among people of Scandinavian descent, but it generally affects about 1 in 150,000 infants. Absence of the enzyme galactocerebroside beta-galactosidase causes increasing destruction of myelin. This results in progressive destruction of the nervous system.

Krabbe disease has an early onset form and a late onset form. In the early form, symptoms begin in the first months of life with feeding problems and failure to thrive, unexplained fevers, and vomiting.

Changes in muscle tone are frequent. Seizures may begin very early and are severe. Visual and hearing losses are progressive. Affected children eventually assume an unusual, rigid body position called decerebrate posturing. Death follows shortly thereafter, usually before the second year of life.

The late onset form of the disease begins in late childhood or early adolescence. Visual problems progressing to blindness may be the first symptom. Gait disturbance (ataxia) and muscle rigidity lead to progressive disability.

Symptoms

     
  • Family history of Krabbe disease, especially in a sibling  
  • Infantile irritability and sensitivity to loud sounds  
  • Feeding difficulties  
  • Vomiting  
  • Failure to thrive  
  • Unexplained fevers  
  • Changing muscle tone from floppy to rigid  
  • Seizures, deterioration in function of nerves in brain and body  
  • Infant who ceases to follow faces or motion (indicates blindness)  
  • Decreased hearing that progresses to deafness

Signs and tests
Examination of the retina may show optic atrophy. Abnormal posturing may be evident (opisthotonos and decerebrate posturing) in late stages of the disorder. There may be signs of deafness.

Tests:

     
  • Galactocerebroside beta-galactosidase levels (levels can be measured from the serum, white blood cells, chorionic villi, and fibroblasts)  
  • CSF total protein may be increased  
  • MRI of the head is the best test to reveal abnormal white matter of the brain  
  • CT of the head  
  • Nerve conduction velocity showing delayed nerve conduction and evidence of demyelination  
  • Presence of abnormal Globoid cells in biopsy tissue of the nervous system  
  • Genetic testing may be available for the glycosylceramidase gene (GALC)

Treatment

There is no specific treatment for Krabbe disease. Bone marrow transplantation (with its own risks) has been attempted in early stages of the disease. It is too early to know if the new bone marrow can fully restore the brain to health in the small number of patients who have had this treatment.

In the future there may be ‘enzyme replacement therapy,’ but it is in the early stages of development as of 2003. Prevention by prenatal or genetic testing is available.

Support Groups
United Leukodystrophy Foundation, (800) 728-5483

Expectations (prognosis)
The outcome is likely to be poor. On average, infantile-onset cases die before 2 years of age. Later-onset cases have survived into adulthood with neurologic disease.

Complications
Progressive central nervous system degeneration occurs. Blindness, deafness, and severe disturbances of muscle tone can result. The disease is usually fatal.

Calling your health care provider
Call your health care provider if your child develops symptoms of this disorder. Seizures, loss of consciousness, or abnormal posturing may be emergency symptoms. Call a genetic counselor if there is a family history of Krabbe disease.

Prevention
Genetic counseling is recommended for prospective parents with a family history of Krabbe disease. Whether you are a carrier for the disease can be determined by testing your white blood cells or skin cells for decreased galactocerebroside beta-galactosidase levels. Prenatal diagnosis is possible by measuring galactocerebroside beta-galactosidase levels in cultured amniotic fluid cells or from cultured chorionic villi cells.

Johns Hopkins patient information

Last revised: December 4, 2012
by Harutyun Medina, M.D.

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