Adult Onset Krabbe Disease Presenting As Complex Form Of CMT, With Peculiar Features On Sural Nerve Biopsy
Peripheral neuropathy is a common feature of classic infantile Krabbe disease and is characterised, on pathological ground, by segmental demyelination, reduction of large myelinated fibers, presence of crystalloid and prismatic inclusions within Schwann cells and histocytes. We report a fifty-nine-year-old man who presented a progressive weakness in his distal limb muscles since the age of forty-seven. At first examination, at the age of 50, there was a slight weakness of small hand muscles and of tibio-peronei (F = 4, MRC scale) with bilateral pes cavus. Reflexes were moderately brisk with bilateral Babinski sign. There was a slight tongue atrophy. Electrophysiological examination showed generalised slowing of nerve conduction velocities. T2-weighted magnetic resonance images showed bilateral periventricular hyperintensity of the white matter. A diagnosis of “complex form” of Charcot Marie Tooth disease was made. Over ten years of follow-up a progressive worsening was observed, particularly in the proximal and distal muscles of his left upper limb. He was intellectually normal. Leukocyte galactocerebroside beta-galactosidase activity, performed at the age of 59, was absent. On sural nerve biopsy the most striking finding was the presence of uniformly thin myelin sheaths without evidence of de-remyelination. Myelinated fiber density was moderately reduced. Two brothers suffered from the same disease. Symptoms started at 41 and 47 years and were characterised by progressive weakness in the limbs with death occurring at 61 and 59 years, respectively, due to respiratory failure. Nerve conduction velocity was slowed in both patients. Sural nerve biopsy was performed in one of them, 4 years before death, and disclosed a complete absence of myelinated and unmyelinated fibers. Parents were not consanguineous and did not suffer from neurological diseases. In conclusion our findings show that peripheral neuropathy may be the presenting feature of late-onset Krabbe disease. We found that hypomyelination rather than demyelination was responsible for slowing of nerve conduction. Our data confirm the only report in the literature (Matsumoto et al., Acta Neuropathol 1996, 92:635) suggesting that hypomyelination may play a role in late-onset Krabbe disease.
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Document Type: Abstract
Affiliations: Neurological Institute, Catholic University, Rome.
Publication date: March 1, 2001