Krabbe disease

The Krabbe disease is a well-known also under the name Krabbe Leukodystrophy disease and belongs to the Sphingolipidoses, a class of storage diseases (see also sphingolipids and cerebrosides ).

The Krabbe's disease is named after the Danish physician Knud Krabbe (1885-1961) and is inherited as an autosomal recessive trait. Cause is a defect in the GALC gene is located on chromosome 14 in the section Q3.1 and serves as a blueprint for the enzyme galactocerebrosidase. The absence of this enzyme leads to the accumulation of substances which are produced during the metabolism of myelin, in particular galactocerebroside and psychosine. Psychosine is toxic to oligodendrocytes, which are necessary for the establishment and maintenance of myelin. The result is a progressive demyelination of the nervous system.

One distinguishes the classic infantile form of late incipient special forms of the disease.

Symptoms

The symptoms usually begins at the age of three to six months. The children are easily irritable and prone to heavy influenced screaming fits. The cognitive- motor development comes to a halt. On external stimuli may lead to tonic extension of the legs. Reflexes are no longer triggered. In optic atrophy leads to blindness.

In the further course of deafness develop a permanent opisthotonos with bent arms and legs stretched out and drooling and fever. In the late beginning of the special forms it comes in the same symptoms, only the disease starts later and runs slower.

Diagnosis

In the cerebrospinal fluid ( CSF) is typically found an increased protein concentration. The nerve is reduced. In imaging reveals the demyelination. In autopsy specimens to monocytes and polynuclear macrophage accumulation ( globoid cells) with PAS -positive, but not metachromatic inclusions in gliotisch altered brain tissue show.

To confirm the diagnosis, one can determine the activity of the enzyme galactocerebrosidase in leukocytes or fibroblasts cultures or perform a genetic analysis. In the latter, there is a mutation in chromosome 14 ( q3 section 1).

Since it is a recessive genetic disease, the risk for siblings is also contracting the disease 25%. By prenatal diagnosis can be a Krabbe disease already diagnose or exclude In Utero. Similarly, one can examine relatives, whether they are carriers of the disease.

Therapy

The disease is not curable. Treatment options are limited to symptomatic therapy or palliative measures. Have proved to pain killers and sedatives and muscle relaxants. In late forms could be achieved in some cases by a stem cell transplant good results.

Forecast

The children die at an average age of about 13 months.

• Disease in neurology
• Neurodegenerative disease
• Lysosomal storage disease