Metachromatic leukodystrophy

The metachromatic leukodystrophy ( from Ancient Greek μετά meta " between ", "in the midst " and ancient Greek χρῶμα chroma " color", see also metachromasia, as well as ancient Greek λευκός leukos "white", ancient Greek δύς dys " bad" and ancient Greek τροφή trophé " food " ) ( MLD, also called arylsulfatase A deficiency ) belongs to the group of the lipid storage diseases ( Sphingolipidoses ). It leads to a degeneration of the white matter or demyelination.

Epidemiology

The incidence is 1:40 000 with specified without gender preference. The disease appears to be inherited as an autosomal recessive trait, with different genes are involved.

Clinic

Depending on the age of onset different subtypes can be distinguished:

  • Late infantile form (40%)
  • Juvenile form (40%)
  • Adult form (20%)

The first symptoms occur in previously normal children on chronic deterioration. The main symptoms first appear unsteady gait, ataxia, loss of language skills as well as flaccid paralysis. In the course of spastic paralysis develop. Also typical is a loss of vision caused by optic atrophy and shows as a characteristic cherry-red spot in the fovea centralis in the funduscopy. Other symptoms include dementia, gallbladder inflammation and the formation of gallstones, which can lead to colic.

Cause

The metachromatic leukodystrophy is caused by a deficiency of arylsulfatase A. Thus, the sulfate group of sulfated glycosphingolipids not split off and the lipids can not be subsequently degraded in the lysosome as usual: They accumulate there. There will be a storage of sulfatide, especially in the myelin sheath of the CNS and PNS, followed by Mark Distinctive generation.

Diagnosis

The disorder of the white matter can be discovered by a cranial magnetic resonance imaging. Typical findings are:

  • Symmetry of the changes
  • Diffuse signal change in the white matter of the cerebrum
  • Early involvement of the beam as well as the brain stem

Differential diagnosis M.Krabbe, ADEM, delineate adrenoleukodystrophy.

The diagnosis is confirmed by determining the arylsulfatase A in urine. As is specific to the decreased activity of arylsulfatase A in leukocytes.

Therapy

A causal therapy is not known, so that symptomatic treatment is paramount. However, there is a new approach after using transgenic, ie modified lentiviruses the intact nucleic acid sequence of the gene responsible for the disease is incorporated into the blood stem cells of the patient. The method makes use of the fact that lentiviruses, such as HIV, integrate parts of their genome into the genome of host cells.

Forecast

The disease generally run within months or a few years deadly.

Swell

  • K. Masuhr, M. Neumann: Dual row - Neurology. Hippocrates Verlag 1998, 4th edition. ISBN 3-7773-1334-3
  • A. Biffi et al. Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy. Science Express, July 11, 2013, DOI: 10.1126/science.1233158.
Metachromasy Autosome Acute disseminated encephalomyelitis Medical diagnosis
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