Peripheral neuropathy detected on electrophysiological study as first manifestation of metachromatic leucodystrophy in infancy.

Abstract

SYNOPSIS A case of infantile metachromatic leucodystrophy is described in which symptoms started at 1 year of age with weakness and hypotonus in the lower extremities. The electrophysiological status was typical of a polyneuropathy, showing fibrillation and a reduction of the nerve conduction velocity to 30%. of the average for normal children of the same age. Clinical signs of a central lesion and mental regression were not evident until a year later. Nerve biopsy showed metachromatic granules in the phagocytes and in the Schwann cells, confirming the diagnosis of metachromatic leucodystrophy. In peripheral neuropathy in infancy without obvious cause, a nerve biopsy is the most appropriate method for diagnosis of the metachromatic leucodystrophy.

A spontaneously immortalized Schwann cell line to study the molecular aspects of metachromatic leukodystrophy

“…Weakness of lower limbs with characteristic lamellar inclusions in Schwann cells and macrophages was observed in MLD patients (Bindu et al, 2005;Fressinaud et al, 1992). Similar reports with peripheral neuropathy in MLD patients were published by different groups (Coulter-Mackie et al, 2002;Hansen et al, 1994;Martinez et al, 1975). In addition, ASA-deficient mice older than 18 months show degeneration of up to 20% of fibers in peripheral nerves (Gieselmann, 2003).…”

Multifocal slowing of nerve conduction in metachromatic leukodystrophy

“…In addition to MLD, other disorders to be considered include Krabbe disease, adrenomyeloneuropathy, Leigh disease, Cockayne syndrome, giant axonal neuropathy, and, in adolescents, cerebrotendinous xanthomatosis. 4 In contrast, when peripheral nervous system findings predominate clinically, 22,25 and there is a significant delay between the onset of these and the subtler central nervous system findings, NCS often have an important role in directing further diagnostic studies. Because infants and children in the early stages of MLD, as well as presymptomatic siblings, may benefit from bone marrow transplantation, early diagnosis is important.…”

“…Motor unit potentials, described in 2 patients, were long-duration, rapidly firing, and polyphasic, with associated fibrillation potentials. 8,22 There are rare reports of multifocal conduction slowing in MLD, but they relate mostly to the adult form. 7,12,35 In 1 case of early juvenile MLD, the initial NCS at 4 years of age revealed nonuniform slowing in distal and proximal segments of the ulnar and peroneal nerves, with differences of 28 and 19 m/s, respectively.…”

“…2,5,15,32 These findings are supported by segmental abnormalities on pathologic studies. 1,16,29 Several investigators have reported on electrophysiologic abnormalities in patients with MLD, mostly in the form of single case reports, 3,8,9,18,22,30,31 although some patient series include late infantile or early juvenile MLD. 13,21,24,28,33 Conduction velocities were significantly reduced (10 -30 m/s) and CMAP amplitudes were diminished or, rarely, normal.…”

“…21,23 Developmental delay or cognitive decline is eventually evident in all forms, as is a sensorimotor demyelinating polyneuropathy. The neuropathy, however, may sometimes precede central nervous system manifestations for as long as 1 year in the late infantile variant 22 and 2 years in the early juvenile form. 21 Very rarely, adults have isolated polyneuropathies that develop years after onset.…”