Fanconi anemia
| Classification according to ICD-10 | |
|---|---|
| D61.0 | Congenital aplastic anemia - Fanconi anemia |
| ICD-10 online (WHO version 2019) | |
The Fanconi anemia (FA) is an extremely rare genetic disease and form of anemia that can affect children and adults of any ethnicity. It leads - in various ways - both to a reduced synthesis of red and white blood cells and to the excessive breakdown of these cells. This disease was named after the Swiss pediatrician Guido Fanconi .
Clinical picture
Typical features of FA can include: congenital malformations (for example of the thumb (see also tripartite thumb polysyndactyly syndrome ), forearms, kidneys, esophagus, hips, ears or the heart), small stature, small head circumference, regression of the bone marrow (severe aplastic anemia), pigment abnormalities of the skin and an extremely increased risk of leukemia and solid tumors (especially mucosal carcinomas ). In the past, Fanconi anemia was almost always fatal. Although the average survival age has risen significantly thanks to improved treatment methods, FA patients still need close and professional care and regular preventive examinations from experienced experts.
As the children get older, the bone marrow almost always regresses (onset from the age of three to five). The severity can vary. Often all three rows of blood cells ( white and red blood cells and the thrombocytes (blood platelets)) are no longer sufficiently formed. The children are noticeably pale and often exhausted after just a little exertion. They are also noticeable through frequent infections, excessive bruising, bleeding from the nose or gums. The greatest life-threatening danger with extremely low blood values is pneumonia and cerebral hemorrhage. Serious threats can only be averted through regular blood counts and timely platelet and erythrocyte transfusions as well as, if necessary, professional treatment with antibiotics, anti-virus and anti-fungal drugs. There is also an increased risk of developing acute myeloid leukemia .
genetics
Fanconi anemia is primarily an autosomal recessive hereditary disease, a chromosome break syndrome . Thirteen different Fanconi anemia subgroups are currently known (as of May 2007). The individual subgroups are named after letters of the alphabet: Fanconi anemia A, B, C, D1, D2, E, F, G, I, J, L, M and N. Over 60% of the cases belong to group A, the The genetic defect is on chromosome 16q24.3 . The gene for subgroup B (FANCB) is an exception: it is located on the X chromosome. Only boys are affected by this Fanconi anemia subgroup. The defect that causes the disease is transmitted from the mother, who is clinically healthy but is the carrier of the disease.
The BRIP-1 gene on chromosome 17q23.2 , also called FANCJ, is responsible for many other cases of FA.
In all of the other FA subgroups discovered so far, the disease occurs equally in boys and girls. It can only arise if both parents are carriers of a genetic defect in the same FA subgroup. Only if this requirement is met is there a 25% risk of the child being affected in any pregnancy. These parents usually only find out about their hidden genetic defect when one of their children is diagnosed with Fanconi anemia.
Epidemiology
It is estimated that there are around five to ten new cases for every million births. There are currently around 200 to 300 affected people living in Germany. Few doctors have sufficient experience with the distinguishing features of Fanconi anemia. It must be expected that a number of FA patients will still be diagnosed relatively late or not at all. Genetic counseling and testing is recommended for all families in whom FA has already occurred. In countries or cultures in which relatives marriages are much more common than in Germany, the proportion of FA patients is higher.
therapy
Treatments with androgen preparations (drugs that contain synthetically manufactured male hormones) can stabilize blood formation for months to years in the majority of patients. If serious side effects occur, the medication must be reduced or discontinued. According to information from the Berlin Charité from 2006, the probability of survival of FA patients with a bone marrow transplant was over 60 to 70% for third-party donors and over 80 to 90% for sibling donors, whereby the protocol for the pretreatment before bone marrow transplants (type and dose of chemotherapy or radiation) or the age of the patient (younger FA patients often tolerate the treatment much better) play a significant role in the chances of success.
FA patients who have survived a bone marrow transplant in the long term are cured of the blood formation disorders. Cells that do not belong to the (foreign) blood-forming system are still affected by the defect. The cell repair function remains disturbed. The patients therefore show a greatly increased risk of cancer for life, especially for mucosal tumors (especially in the mouth, throat, esophagus and genital area). Like FA patients without a bone marrow transplant, they must undergo regular checkups so changes can be diagnosed and treated promptly. Research is currently not yet clear whether the increased risk of cancer in transplanted FA patients is to be understood as an after-effect of the treatment to destroy their own bone marrow before the transplant (today in Germany mostly only individually adapted chemotherapy, early chemotherapy and radiation) .
Web links
- FA Handbook of the German Fanconi Anemia Help e. V. (2005 edition, PDF, 380 pages, 2.9 MB)
- Link catalog on the subject of Fanconi anemia (English) at curlie.org (formerly DMOZ )
Individual evidence
- ^ BP Alter: Fanconi anemia and the development of leukemia. In: Best practice & research. Clinical haematology. Volume 27, number 3-4, 2014 Sep-Dec, ISSN 1532-1924 , pp. 214-221, doi : 10.1016 / j.beha.2014.10.002 , PMID 25455269 , PMC 4254647 (free full text).
- ↑ B. Frank et al: BRIP1 (BACH1) variants and familial breast cancer risk: a case-control study. In: BMC Cancer , 7/2007, p. 83. PMID 17504528
