Metachromatic Leukodystrophy

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Classification according to ICD-10
E75.2 Other sphingolipidoses
Metachromatic leukodystrophy
ICD-10 online (WHO version 2019)

The metachromatic leukodystrophy (from ancient Greek μετά meta , German , between, after ' (and in terms of a deviation) ancient Greek χρῶμα chroma , German , color' , see also Metachromasia , as well as ancient Greek λευκός leukós , German , white ' , ancient Greek δύς DYS , German 'Bad' and ancient Greek τροφή trophé , German 'nutrition' ), MLD, also called aryl sulfatase A deficiency, belongs to the group of lipid storage diseases ( sphingolipidoses ). It leads to white matter degeneration or demyelination .

Epidemiology

The frequency is given as 1: 40,000 without gender preference. The disease appears autosomal - recessive to be inherited, with different genes are involved.

clinic

Depending on the age of onset, a distinction is made between various sub-forms:

  • Late infantile form (40%), synonyms: metachromatic leukodystrophy type Greenfield; late infantile form
  • Juvenile form (40%), synonyms: Metachromatic leukodystrophy type Scholz; juvenile form
  • Adult form (20%), synonyms: Metachromatic leukodystrophy Austin type; adult form

The first symptoms appear in previously inconspicuous children with chronic deterioration . The main symptoms are unsteady gait, ataxia , loss of language skills and flaccid paralysis . Spastic paralysis develops over time. A loss of vision caused by optic atrophy is also typical and can be seen in the fundus of the eye through a blown papilla. Other symptoms include dementia, inflammation of the gallbladder, and the formation of gallstones , which can lead to colic .

root cause

Metachromatic leukodystrophy is a lack of arylsulfatase A caused. As a result, the sulphate group of sulphated glycosphingolipids cannot split off and the lipids cannot subsequently be further degraded in the lysosome as is usual : they accumulate there. There is a storage of sulfatide mainly in the myelin sheaths of the CNS and PNS with subsequent myelin sheath degeneration.

diagnosis

The white matter disorder can be detected by a skull magnetic resonance imaging . Typical findings are:

The differential diagnosis are M.Krabbe , ADEM , adrenoleukodystrophy and multiple sulfatase deficiency delineate.

The diagnosis is confirmed by the determination of aryl sulfatase A in the urine . The reduced activity of aryl sulfatase A in leukocytes is considered specific .

therapy

No causal therapy is known, so symptomatic therapy is the main focus. However, there is a new approach according to which the intact nucleic acid sequence of the gene responsible for the disease is integrated into the patient's blood stem cells with the help of transgenic, i.e. modified, lentiviruses . The method makes use of the fact that lentiviruses such as HIV, for example, integrate parts of their genome into the genome of the host cells. Clinical studies are investigating the administration of genetically engineered aryl sulfatase A into the brain via a catheter.

forecast

The diseases are usually fatal within months or a few years.

swell

  • K. Masuhr, M. Neumann: Dual Series - Neurology. 4th edition. Hippokrates Verlag, 1998, ISBN 3-7773-1334-3 .
  • A. Biffi et al .: Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy. In: Science Express. July 11, 2013, doi: 10.1126 / science.1233158 .

Individual evidence

  1. ↑ a b J. P. Kuhn, TL Slovis, JO Haller (Ed.): Caffey's Pediatric Diagnostic Imaging. 10th edition. Mosby, 2004, ISBN 0-323-01109-8 .
  2. ↑ - ( Memento of the original from December 30, 2013 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. MLD Foundation. @1@ 2Template: Webachiv / IABot / www.mldfoundation.org
  3. ↑ a b M. van derKnaap, J. Valk: Magnetic Resonance of Myeliation and Myelin Disorders. Springer, 2005, ISBN 3-540-22286-3 .
  4. ↑ Bernfried Leiber (founder): The clinical syndromes. Syndromes, sequences and symptom complexes . Ed .: G. Burg, J. Kunze, D. Pongratz, PG Scheurlen, A. Schinzel, J. Spranger. 7., completely reworked. Edition. tape 2 : symptoms . Urban & Schwarzenberg, Munich et al. 1990, ISBN 3-541-01727-9 .
  5. ↑ a b - ( Memento of the original dated December 31, 2013 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Myelin Project: Metachromatic Leukodystrophy. @1@ 2Template: Webachiv / IABot / myelin.de
  6. ↑ Alessandra Biffi et al .: Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy. 2013.
  7. ↑ https://clinicaltrials.gov/ct2/show/NCT01510028 .

Web links