What is Krabbe Disease (Globoid Cell Leukodystrophy)?
Krabbe disease (globoid cell leukodystrophy) is a rapidly progressive demyelinating degenerative disease of the central nervous system.
Causes of Krabbe Disease (Globoid Cell Leukodystrophy)
The type of inheritance is autosomal recessive. The basis of the disease is a decrease in the activity of the enzyme galactosilceramide-b-galactosidase, which normally cleaves galactocerebroside to ceramide and galactose.
Pathogenesis during Krabbe Disease (Globoid Cell Leukodystrophy)
Galactocerebroside and its derivative psychosin accumulate in the brain, liver, spleen, kidneys, leukocytes, fibroblasts. The amount of the latter increases 10-100 times, which has a toxic effect on oligodendroglial cells that form the myelin sheath. In the demyelination zones around the small blood vessels, the white matter contains a large number of globoid histiocytes (macrophages). Decrease in oligodendroglial cells is accompanied by gliosis. Peripheral nerves undergo axonal degeneration with an accumulation of foamy histiocytes.
Symptoms of Krabbe Disease (Globoid Cell Leukodystrophy)
As a rule, the first clinical symptoms appear in the fourth month of life. Anxiety and muscle hypertension are noted. The upper and lower limbs of sick children are in a bent state, their fists clenched. Soon, psychomotor retardation becomes noticeable. Later, myoclonic seizures, generalized motor response to auditory stimuli, spastic tetraparesis, increased deep tendon reflexes develop, and in the study of the fundus of the eye there is atrophy of the optic nerves. Manifestations of peripheral neuropathy are found only in individual cases. Subsequently, characteristic deep mental disorders, sluggish tetraparesis develop, tendon reflexes decrease, muscle hypertension is replaced by hypotension. Patients die at the age of 7 months to 3 years.
Diagnosis of Krabbe Disease (Globoid Cell Leukodystrophy)
The diagnosis is based on the clinical picture, the increase in the protein content in the cerebrospinal fluid, the detection of a decrease in the activity of galactosilceramide-b-galactosidase. Differential diagnosis is carried out with other forms of leukodystrophy on the basis of biochemical analysis.
Treatment of Krabbe Disease (Globoid Cell Leukodystrophy)
Specific treatment is not developed. Prenatal diagnosis of Krabbe’s disease is possible by examining galactosylceramide-b-galactosidase activity in cultured amniotic cells.