Krabbe leukodystrophy. Globoid cell leukodystrophy. Late onset (late infantile and juvenile form). Galactosylceramidase (galactocerebrosidase beta-galactosidase) deficiency.
Incidence
It is very rare. AR. Only 23 cases reported up to 1987 and 40 more patients between 1987 and 1990. It accounts for 10 to 15 % of all cases of Krabbe leukodystrophy. It has a world wide distribution. Seems to be especially frequent in Southern Italy.
Clinical Characteristics
The disorder starts between age fifteen months and ten years. Mostly before age five years. There is no significant difference in symptoms between late infantile and juvenile form. There is an equinovarous deformity of the feet that is progressive and may be present for several years before other symptoms and signs are appreciated. Gait difficulty in a previous normal or mildly retarded child is usually the first indication of the condition. Spastic paraparesis with pyramidal signs, cerebellar ataxia or a combination of both are the main features neurologically. Occasionally a spastic hemiplegia may begin the clinical picture, but it is followed by bilateral involvement later. Dystonia occasionally has been reported. There is involvement of peripheral nerves from the onset of the disease in some patients. Half of the patients have absent deep tendon reflexes and/or slow nerve conduction velocity. With the progression of the disease, the neuropathy is more obvious. There is optic atrophy and visual failure in most patients in the advanced stage of the disease (in 20 % of cases it can be the initial finding). Blindness is related to optic atrophy in early onset cases and demyelination of optic radiation in later onset variants. Seizures are frequent and occasionally they may be severe. Dementia appears progressively after the onset of motor signs. Some patients may remain normal mentally. Occasionally it can be presented as behavioral changes with irritability and intellectual impairment. Some 50 % of cases have high protein in spinal fluid. MRI of the brain show periventricular parietal occipital areas of demyelination. CT scan may be normal in the early stage. Sural nerve biopsy shows segmental demyelination. If the nerve conduction velocity is normal, the nerve biopsy is normal also. Most patients become tetraplegic and demented after a period of two to five years but other patients may be alive after one or two decades. Sometimes, infections may worsen the disease. It is an autosomal recessive disorder. The brain pathology is similar to the classical early infantile disease. There is deficiency of galactocerebroside betagalactosidase in leukocytes and fibroblasts as severe as in the early infantile type. The more important symptoms and signs are progressive spastic paraplegia, progressive cerebellar ataxia, progressive visual failure with optic atrophy and cortical blindness, slowly progressive hemiplegia, peripheral neuropathy and absence of visceral involvement. Be aware that 50% of cases have normal nerve conduction velocity and normal CSF protein in contrast to early infantile form . In this cases, diagnosis is done by the specific enzymatic defect.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
EB-W, EB-F There is deficiency of galactocerebroside betagalactosidase in leukocytes and fibroblasts as severe as in the early infantile type. Sural nerve biopsy shows segmental demyelination. In 50 % of cases there is high protein in spinal fluid.