Günther's disease

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Classification according to ICD-10
E80.0 Hereditary erythropoietic porphyria
ICD-10 online (WHO version 2019)

The Günther's disease or Günthersche disease (also congenital erythropoietic porphyria ., Abbr CEP, and porphyria congenita ) is a rare autosomal - recessive inherited disease (<1: 1,000,000), which manifests itself in childhood. That of mutation affected gene encodes for the III synthase uroporphyrinogen , an enzyme of porphyrin - metabolism . The disease is named after the German doctor Hans Günther (1884–1956).

The technically incorrect name Günther's disease is also understood in some places to mean a number of diseases that are related to the use of ammunition containing uranium . The clinical picture was described by the German doctor Siegwart-Horst Günther in the early 1990s .

Pathogenesis

CEP is a hereditary disorder of the biosynthesis of heme , the iron-containing pigment in red blood cells . Together with the globins, heme forms hemoglobin, which is located on the red blood cells and is necessary for the transport of oxygen.

The disease is caused by a decreased activity of uroporphyrinogen III synthase , one of the 8 enzymes required for the synthesis of heme. This is followed by an accumulation of hydroxymethylbilane , which the affected enzyme should "further process".

Symptoms

For most people, the first symptoms manifest themselves at birth or in early childhood. CEP is characterized by photosensitivity of skin areas exposed to light; this can lead to greater fragility, the development of bubbles or even to photomutilation (severely disfiguring photodermatosis ). The latter is due to an accumulation of the heme precursor uroporphyrinogen I in the skin, bones and other tissues. Hypertrichosis , focal hyper / hypopigmentation and skin thickening can occur. The severity of a person's symptoms can vary.

The first manifestation of CEP is often pink to red, fluorescent urine. Hemolytic anemia and splenomegaly (enlarged spleen) are common. A red discoloration of the teeth (erythrodontia) is pathognomonic for CEP.

Unlike erythropoietic protoporphyria, there is no swelling, pain, or itching during or after exposure to light.

diagnosis

Detection of uroporphyrinogen I in the urine using HPLC .

The first signs of CEP in the newborn may be pink / dark red colored urine. This is particularly important in connection with the phototherapy used in neonatal jaundice , as infants with CEP can get the most severe, disfiguring burns. Since CEP is inherited recessively, the parents are usually not affected, so that there is no family history that would suggest a CEP in the newborn.

therapy

Gene therapy as a causal therapy was successfully carried out on mice in 2008.

Sun protection is particularly important, as exposure to the sun causes the strong skin symptoms. An allogeneic stem cell transplant may be considered. In this way, the defective cells are replaced, with the disadvantage of lifelong immunosuppression, of course .

forecast

The prognosis is unfavorable given concerns about the severity of the disease and the available therapy options.

confusion

The CEP is not to be confused with the Xeroderma pigmentosum ("moonlight children") caused by skin damage by UV light , which is based on a failure of the ability to repair DNA damage in the skin.

Trivia

The symptoms of pallor due to the existing anemia , disfigurement of the face due to photodermatosis , nocturnal lifestyle due to the sensitivity to light and reddish teeth suggest that early cases of Günther's disease may have contributed to the development and / or formation of the vampire myth. Cases of increased body hair should also be observed in M. Günther, which would also encourage the legend. In addition, due to the content of cytochrome P450, which can intensify the existing hemolysis , it is not uncommon for patients to react intolerably to garlic and related plants. The literary vampire templates and real porphyria symptoms, which are in any case not uniform from author to author, often differ from one another, but with most authors and among the common popular vampire legends, at least partial matches with the listed symptoms can regularly be found.

Individual evidence

  1. ↑ annals.edu.sg .
  2. ↑ indianpediatrics.net
  3. ↑ H. de Verneuil, E. Robert-Richard, C. Ged, F. Mazurier, E. Richard, F. Moreau-Gaudry: Successful gene therapy of mice with congenital erythropoietic porphyria . In: Med Sci (Paris) . tape 24 , no. 6-7 , 2008, pp. 615-620 , PMID 18601879 (French).
  4. ↑ Urs-Nikolaus Riede, Martin Werner, Hans-Eckart Schaefer: General and special pathology. Thieme Verlag, year ?, ISBN ?, p.?
  5. ↑ AM Cox: Porphyria and vampirism: Another myth in the making. In: Postgraduate medical journal. Volume 71, Number 841, November 1995, pp. 643-644, PMID 7494765 , PMC 2398345 (free full text).

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