Pelizaeus-Merzbacher disease

from Wikipedia, the free encyclopedia
Classification according to ICD-10
E75.2 Other sphingolipidoses
ICD-10 online (WHO version 2019)

The Pelizaeus-Merzbacher disease is a rare congenital disease of the central nervous system . In this disease from the group of leukodystrophies , a myelination disorder occurs , which can cause a variety of symptoms. The disease is named after Friedrich Christoph Pelizaeus and Ludwig Merzbacher, who first described it.

genetics

Pelizaeus-Merzbacher's disease is based on a mutation of the gene coding for proteolipid protein 1 (PLP1) on the X chromosome (Xq22). The mutation leads to the failure or uselessness of PLP1 production and subsequently to an incorrect composition of the myelin sheaths , which are necessary for the normal function of the nerve fibers . The inheritance of Pelizaeus-Merzbacher disease is X-linked recessive, which is why usually only boys and men are affected. The genetic changes in the PLP1 gene observed in the disease are manifold: in addition to deletions , duplications of the PLP1 gene have also been described. The disease belongs to the disease group of hereditary spastic spinal paralyses or spastic paraplegia . There it is called SPG2 (spastic paraplegia gen 2).

Symptoms

The main symptoms of Pelizaeus-Merzbacher disease are a delay in normal mental and motor development with uncontrollable, rhythmic movements of the eyes ( nystagmus ), paralysis of the muscles (whereby both spastic and flaccid paralysis with loss of tone, especially of the trunk muscles, can occur) and a stance - and unsteady gait ( ataxia ). The disease usually begins in infancy or childhood, but can also only manifest itself in adulthood.

Classification

According to WO Renier and employees, there are three types of classification:

  1. Classic form with manifestation in the first months of life, nystagmus , muscle hypotonia later changing into spasticity , ataxia and impaired motor development appear in the course .
  2. Congenital form with rapid deterioration from birth with additional dyspnoea and stridor and development of spastic tetraparesis
  3. Transitional form with degree of impairment between the classical and the connatal form.

Related diseases

Diseases that are similar to Pelizaeus-Merzbacher disease, but are inherited as an autosomal recessive trait, are:

  • Pelizaeus-Merzbacher like disease (PMLD) 1: caused by mutations in connexin -47 (GJA12) gene on chromosome 1q41
  • Pelizaeus-Merzbacher like disease (PMLD) 2

A disease that is similar to Pelizaeus-Merzbacher disease, but is inherited in an autosomal dominant manner and the onset of the disease is in adulthood

  • autosomal dominant leukodystrophy (ADLD).

Diagnosis

Neurological examination and anamnesis may reveal initial suspicions. However, biochemical markers for the disease do not exist. The magnetic resonance imaging of the brain has disorders of the marrow maturation ( myelination ) which, however Merzbacher disease Pelizaeus are not specific to the. A differentiation from demyelinating diseases can be done with the help of magnetic resonance spectroscopy. Evidence is provided by molecular genetic evidence of a mutation in the PLP1 gene on the X chromosome (Xq22). A prenatal diagnosis is possible.

treatment

The cause of Pelizaeus-Merzbacher's disease cannot be treated. Supportive care, including emotional support for family members, is recommended as needed. Physiotherapeutic and occupational therapy treatment aims to improve the quality of life of the affected children.

forecast

The severity of the disease varies significantly, among other things, depending on the type of PLP mutation and ranges from mild courses in diseases that only manifest themselves in adulthood to the most severe forms that start in infancy and fatal in childhood.

Individual evidence

  1. ↑ Pelizaeus: About a peculiar form of spastic paralysis with cerebral symptoms on a hereditary basis (multiple sclerosis). Arch. Psychiat. Nerve crisis 1885; 16, p. 698.
  2. ↑ Merzbacher: A peculiar form of familial hereditary disease (aplasia axialis extracorticalis congenita). In: Journal for the whole of neurology and psychiatry. 1910; 3, pp. 1-138.
  3. ^ Koeppen, Robitaille: Pelizaeus-Merzbacher disease. In: J Neuropathol Exp Neurol . 2002; 61 (9), p. 747. PMID 12230321
  4. ↑ Garbern: Pelizaeus-Merzbacher disease: Genetic and cellular pathogenesis. In: Cell Mol Life Sci. 2007; 64 (1), pp. 50-65. PMID 17115121
  5. ↑ WO Renier, FJ Gabreëls, TW Hustinx, HH Jaspar, YES Geelen, UJ Van Haelst, EJ Lommen, BG Ter Haar: Connatal Pelizaeus-Merzbacher disease with congenital stridor in two maternal cousins. In: Acta neuropathologica. Vol. 54, No. 1, 1981, pp. 11-17, ISSN  0001-6322 . PMID 7234326 .
  6. ^ Pelizaeus-Merzbacher disease. In: Orphanet (Rare Disease Database).
  7. ↑ PMLD 1.  In: Online Mendelian Inheritance in Man . (English)
  8. ↑ PMLD 2.  In: Online Mendelian Inheritance in Man . (English)
  9. ↑ ADLD.  In: Online Mendelian Inheritance in Man . (English)
  10. ↑ Hanefeld et al.: Quantitative proton MRS of Pelizaeus-Merzbacher disease: evidence of dys and hypomyelination. In: Neurology. 2005; 65 (5), pp. 701-706. PMID 16157902
  11. ↑ Garbern, Hobson: Prenatal diagnosis of Pelizaeus-Merzbacher disease. In: Prenat Diagn. 2002; 22 (11), pp. 1033-1035. PMID 12424770

Web links