Krabbe leukodystrophy. Globoid cell leukodystrophy. Early infantile form. Galactosylceramidase (galactocerebrosidase beta-galactosidase) deficiency.
Incidence
It is an autosomal recessive disorder. It occurs in most parts of the world but more prevalent in Sweden. More than one hundred and ten patients have been recorded.
Clinical Characteristics
In the majority of cases, the disease starts between three and six months and has a rapidly fatal outcome. Clinically is characterized by generalized rigidity with tonic spasms in association with clinical and electrophysiological evidence of peripheral nerve involvement and high CSF protein level. There is extensive demyelination in the central and peripheral nervous system. The pathological hallmark of the disease is the presence of multinucleated macrophages containing galactocerebrosides, called globoid cells. In a few cases, the onset is in late infancy. In 80 % of the cases, the disease begin before age six months and in 25 % before age three months. The first signs are irritability with crying spells, diminished alertness, vomiting and sitting problems. Rigidity is a very striking abnormality. The muscle hypertonia increases progressively affecting the whole body. Tonic spasms induced by any kind of stimulation and sitting lead to opistotonic position. Startle response may occur rarely. Pyramidal signs with increased tendon reflexes and Babinsky are initially present but then disappear as the spasticity decrease. Peripheral nervous system is affected early in the disease. Nerve conduction velocity are very slow. Blindness and optic atrophy appear later with pendular nystagmus and strabismus which are often the first signs of visual failure. Optic atrophy is a late finding. Occasional deafness is observed. Unexplained fever may occur. Seizures may occur but seldom are a major sign. EEG is abnormal non specific showing slow wave activity but may be normal initially. Protein in spinal fluid is high from 72 to 450 mg percent and can be present before symptoms are apparent. Very occasionally, CSF is normal. Head size is normal initially but then becomes small. Failure to thrive is very evident. The course of the disease is relatively brief and death before one year occur in 70% of the cases. Death is usually due to respiratory difficulty and pneumonia. Diagnosis is made by examining the spinal fluid showing marked elevation of protein, slow nerve conduction velocity and abnormal MRI which shows central white matter demyelination starting usually in the periventricular region of the posterior part of the brain. Measurement of the enzyme galactosylceramidasa (galactocerebroside beta-galactosidase is done in leukocytes or cultured fibroblasts. There is no specific treatment.
Precipitants
no. Tonic spasms induced by any kind of stimulation and sitting lead to opistotonic position. Startle response may occur rarely.
Provocation Tests
no
Diagnostic Procedures
EB-W, EB-F. Diagnosis is made by examining the spinal fluid showing marked elevation of protein, slow nerve conduction velocity and abnormal MRI which shows central white matter demyelination starting usually in the periventricular region of the posterior part of the brain. Measurement of the enzyme galactosylceramidasa (galactocerebroside beta-galactosidase is done in leukocytes or cultured fibroblasts.