Beta Galactocerebrosidase (GALC) Deficiency; Galactosylceramide Deficiency; Galactosylceramide Lipidosis; Globoid Cell Leukodystrophy (GLD); Krabbe Leukodystrophy; Sphingolipidoses, Krabbe type

Krabbe disease (KD) is a rare, inherited degenerative disorder of the central and peripheral nervous systems. Krabbe disease is one of a group of genetic disorders called the leukodystrophies. These disorders impair the growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers, and cause severe degeneration of mental and motor skills. Myelin, which lends it color to the “white matter” of the brain, is a complex substance made up of at least 10 different enzymes. Each of the leukodystrophies affects one (and only one) of these substances. Krabbe disease is a lysomal storage disease caused by a deficiency of galactocerebrosidase (GALC), an essential enzyme for myelin metabolism.

Infantile form: This is the most common type and onset is almost always before 6 months of age and even during the first week of life. The baby usually dies within the first one or two years of life, most commonly due to infection and/or bulbar palsy.

Diagnostic testing: Before birth, a fetus can be screened for Krabbe disease. Using a needle, the doctor can withdraw amniotic fluid surrounding the fetus, and then the cells in this fluid can be examined in the lab. This requires obtaining fetal cells by chorionic villus sampling or culturing amniotic fluid cells obtained by amniocentesis. After birth, a physical exam of the child, evaluating signs and symptoms and diagnostic testing including: blood, skin (biopsy) samples, lumbar puncture (spinal tap), MRI and CT scans, nerve conduction studies, eye exam, and genetic testing may be done to confirm the diagnosis.

Physical findings:

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  Restlessness;

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  Intermittent fever;

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  Irritability and progressive stiffness (irritable-hypertonic presentation);

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  Fever without infection;

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  Convulsions may be part of the symptoms. There are also

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  Increased muscle tone and pyramidal signs;

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  Absent or weak deep tendon reflexes;

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  Rapid deterioration in motor function, with chronic opisthotonos and myoclonic jerking;

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  Hyperpyrexia, hypersalivation, and hypersecretion from the lungs; and

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  Rapid and severe motor and mental deterioration.

ICD-9: 330.0

Infantile Krabbe disease is generally fatal before age 2. Prognosis may be significantly better for children who receive umbilical cord blood stem cells prior to disease onset or early bone marrow transplantation.

There is no specific, proven treatment for advanced, symptomatic Krabbe disease. Treatment at this stage is designed primarily to ease symptoms. For example, anticonvulsant medications may be used to manage the seizures associated with this disease. Other drugs may reduce the risk of vomiting. Some research indicates possible benefits associated with the use of bone marrow transplantation or cord blood transfusion as treatments for Krabbe disease. For pre symptomatic infants and older individuals with mild symptoms, hematopoietic stem cell transplantation (HSCT) with cord blood provides a benefit over symptomatic treatment only.

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  Genetic testing of GALC gene (targeted mutation or sequence analysis);

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  Enzyme assay for GALC enzyme activity;

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  MRI or CAT scan with characteristic white matter abnormalities; and

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  A description of motor findings (limb stiffness, spasticity, ataxia, progressive psychomotor decline).

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