Abstract Details

Title Correlation between Sural Nerve Sulfatide Accumulation and Severity of Peripheral Neuropathy in Metachromatic Leukodystrophy

Topic Child Neurology/Developmental Neurobiology

Presentation(s) P02 - (-)

Poster/Presentation
Number 091

Objective

Background BACKGROUND: The disease is characterized by progressive spasticity, gait difficulties and psychomotor delays. Pathologically, MLD is associated with neuronal loss and demyelination of the central (CNS) and the peripheral (PNS) nervous systems.

Design/Methods DESIGN/METHODS: We report baseline clinical, biochemical, pathological, and electrophysiological findings in 12 children (8 girls/4 boys; age 2-5 years) before intravenous replacement therapy with recombinant human ASA. Nerve conduction studies (NCS) were carried out in the sural, median and peroneal nerves. Electron and light microscopic studies and sulfatide and lysosulfatide (ng/mg dry weight) measurements were obtained from the right sural nerves.

Results RESULTS: NCS revealed demyelinating neuropathy in 10 patients, whereas two had normal findings. Compared with 4 control sural nerve biopsies (aged 2 months, and 2, 3, and 11 years) there was variable loss of large myelinated fibers, thin myelin, reduced slope of the myelin/fiber thickness relationship, and increased g-ratios. The nerve fiber loss correlated with electrophysiological abnormalities. The two patients with normal NCS had abnormalities on biochemical and EM analysis of the sural nerves. The sulfatide and lysosulfatide levels correlated with the loss of large myelinated fibers in the nerve and with reduced motor and sensory conduction velocities and amplitudes of motor and sensory compound action potentials.

Conclusions CONCLUSIONS: The results indicate that the main pathological abnormality is demyelination with axonal loss, and suggest that the extent of sulfatide and lysosulfatide accumulation is proportional to the severity of damage to nervous tissue in MLD. The studies suggest that the severity of neurological disease and nerve damage are due to the toxic effect of raised sulfatide and lysosulfatide content.

Authors/Disclosures
Christian Krarup, MD, DMSc, FRcP, FAAN (Rigshospitalet) PRESENTER	Dr. Krarup has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Shire/Takeda. Dr. Krarup has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Shire/Takeda. Dr. Krarup has received publishing royalties from a publication relating to health care.
Daniel M. Harrison, MD, FAAN (University of Maryland School of Medicine)	Dr. Harrison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon Therapeutics. Dr. Harrison has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American College of Physicians. The institution of Dr. Harrison has received research support from Roche-Genentech. Dr. Harrison has received publishing royalties from a publication relating to health care.
Christine I. Dali, MD	Dr. Dali has received personal compensation for serving as an employee of Orphazyme A/S .
	No disclosure on file
	No disclosure on file
Norman W. Barton, MD, PhD	Dr. Barton has received personal compensation for serving as an employee of Takeda Pharmaceutical Co. LTD. Dr. Barton has received stock or an ownership interest from Takeda Pharmaceutical Co. LTD.

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