Krabbe disease

Krabbe diseaseKrabbe disease (also known as globoid cell leukodystrophy or galactosylceramide lipidosis,diffuse globoid body sclerosis ) is a rare inherited disorder that causes neurodegeneration.

Description
Krabbe disease is a form of sphingolipidosis and affects myelin sheath of the nervous tissue Usually the disease occur during infancy, although the cases of tha later onset have also been reported. The main symptoms of the disease include seizures, mental and psychomotor retardation, sight and hearing loss.

As long as there is no cure for the disorder most children die before the age of 2.

Cause
Disorder is caused by the disturbed sphingolipids metabolism. The disease is inherited in an autosomal recessive pattern and mutation in the GALC gene locate on chromosome 14 (14q31) that controls the function of the galactosylceramidase.This enzyme is stored in lysosomes and is rezuired to hydrolyze specific galactolipids (galactosylceramide and psychosine) that are involved in the metabolism of myelin. In case of the Krabbe disease galactolipids are accumulated in so-called globoid cells.


Risk factors
The incidence of the disorder is higher among the Scandinavians.

Symptoms
After the birth babies seem to be healthy. The first symptoms appear when the kids are at the age between 3 and 6 months, although sometimes the disorder has a late onset and occur when a child is older or in adolescence. According to the age of the manifestation of the disease are distinguished 4 subtypes:

    • Type 1 – Infantile (classic) form and occurs in the majority of cases (about 85-90%). This type develops gradually in 3 stages. The stage 1 involves the initial symptoms of the disease. During the stage 2 siezures and psychomotor retardation occur. Stage 3 includes severe impairment of the neurologic development, loss of voluntary movements and decerebrate posturing (the involuntary extension of the upper extremities).
    • Type 2 – Late infantile is characterized by the development of the first symptoms when a child is older.
    • Type 3 – Juvenile form of the disease occur when a child is at the age of 3-8 years. At first the regression of the psychomotor functions is fast, but later it is followed by the slower degeneration.
    • Type 4 – Adults experience a big variety of symptoms and different tempto of its progression.

 

Usually the beginning of the disease is characterized by the irritability, fever without any visible cause, hypertonia, hyperesthesia, seizures, persistent vomiting, muscle spasms and change of the muscle tone, difficulties while feeding, delays in psychomotor and mental development. The children also experience loss of developmental abilities as the disease progresses and gradually decreasing hearing and sight. The muscles are stiff and rigid.

Late onset of the disease is associated with slower progression of the clinical symptoms. It is believed that the prognosis for such patients is better.

[See also:Kufs disease]


Diagnosis
To confirm the diagnosis the Galactosylceramide beta-galactosidase (GALC) activity measurement is required. Genetic counseling is also necessary. The analysis of cerebrospinal fluid reveals elevated protein levels along with abnormal protein electrophoresis pattern. Brain CT or MRI may reveal symmetric atrophy of the cerebral tissue and areas of demyelination.

Treatment
Nowadays the most spread treatment of the Krabbe disease is bone marrow transplantation. Hematopoietic stem cell transplantation (HSCT) is considered to be a  potential treatment of the disease. Physical therapy is performed to maintain the state of the muscles. Symptomatic therapy is used to prevent the progression of the disease and provide supportive care for the affected person.