Diamond Blackfan Syndrome

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Classification according to ICD-10
D61.0 Congenital aplastic anemia
- Blackfan-Diamond anemia
ICD-10 online (WHO version 2019)

The Diamond-Blackfan anemia (lat. Erythrogenesis imperfecta ), and Diamond-Blackfan anemia (DBA) or chronic congenital hypoplastic anemia called, is a severe chronic anemia with a too low number of red blood cells in affected mostly already during the occurs in the first year of life.
Its cause has the anemic disease, a special form of aplastic anemia , in the selective disruption of the formation of erythrocytes (red blood cells) in bone marrow. Other hereditary diseases or malformations also occur in around 25% of those affected (see diagnosis ).

history

Louis Diamond and Kenneth Blackfan described hereditary hypoplastic anemia for the first time in 1938. In 1961, Diamond and his colleagues presented a longitudinal study over 25 years based on data from 30 patients and found an association with abnormalities in the skeletal structure.

In 1997, the area on chromosome 19 was identified that carries the corresponding mutated gene of Diamond-Blackfan syndrome.

In 1999, it was found that mutations in the ribosomal protein -S19 gene (RPS19) are responsible for the disease of 42 of 172 DBS patients.

In 2001 it was discovered that a second gene responsible for Diamond-Blackfan Syndrome is on chromosome 8 .

etiology

Autodominant 01.png

The disease can autosomal - recessive or - dominant hereditary be. The change is located on the long arm of chromosome 19 at position 13. In most people affected, the disease occurs sporadically. In around 15% of those affected, the disease was passed on from their parents to their children. The actual cause of the occurrence of the disease is not yet known. It is thought that a congenital red cell stem cell abnormality could be responsible for the disease. As a result of this anomaly, the erythrocyte stem cells in the bone marrow can no longer be stimulated enough by erythropoietin to divide, so that those affected develop anemia with an insufficient number of red blood cells.

Occur

Diamond Blackfan Syndrome is an extremely rare disease. With a frequency of 0.3 diseases per 100,000 people, aplastic anemia (including the special forms of Fanconi anemia and Diamond-Blackfan syndrome) are so rare in Europe that most medical professionals are never confronted with this disease during their entire working hours. The frequency of DBAs is around 5 - 7 cases per 1 million live births.

Around 800 cases have been described worldwide; there are currently around 130 patients in Germany.

Symptoms

Anemia usually manifests itself in the first six months of life, in around half of the cases before the third month of life, in around a third of the cases even at birth or in the first month of life with paleness. People with Diamond-Blackfan syndrome can often have malformations of the body, such as a cleft lip and palate , a small skull ( microcephalus ), small eyeballs ( microphthalmos ), wide-spaced eyes ( hypertelorism ) and a high palate. Half of those with Diamond Blackfan Syndrome are short. One third of those affected have a heart defect , malformation of the kidneys or malformations of the fingers, especially the thumb. In addition, the mental development of affected children can be delayed.

The combination of congenital hypoplastic anemia and certain malformations - such as triphalangia of the thumb, hydrocephalus , cleft lip and palate and multiple joint contractures - is called Aase syndrome or Aase-Smith syndrome II . It is unclear whether it is actually a separate clinical picture or a variant of Diamond Blackfan Syndrome.

diagnosis

Characteristic a is Erythroblastenmangel ( " congenital Erythroblastophthise "; Erythroblastophthise = loss of erythropoietic tissue in the bone marrow, a aplastic anemia in the narrow sense) having reticulocytopenia which possibly with abnormalities of the sexual tract, pseudomongoloidem habit (typical facial expression), microcephaly (abnormal smallness of the cranium) , Microphthalmos ("small eye"), hypertelorism (large eye relief), high palate ( Gothic palate ), as well as a lag in mental and physical development.

While the hemoglobin value (Hb) in the blood of healthy people is above 11 g / dl, it can be below 6 g / dl with a DBA. The diagnosis of DBA can be confirmed by a bone marrow puncture after analyzing the blood with typical changes . In DBA patients, there are no or only little maturing precursor cells of the red blood cells in the bone marrow .

In about 20 to 25% of DBA patients, the disease can be diagnosed by genetic testing via the mutation of the RPS19 gene.

therapy

The disease can be treated well with corticosteroids . In one study, 82% of patients initially responded to corticosteroid therapy with red blood cell formation. This corticosteroid treatment should only be started after the first year of life.

Blood transfusions are used to treat DBAs in the first year of life or in patients who are unresponsive to corticosteroid treatment . An accumulation of iron in the body, a so-called hemosiderosis , must be prevented from the age of three with so-called chelating agents such as deferoxamine . During treatment with transfusions and corticosteroids, periods of remission may occur during which no transfusions or steroid administration are necessary.

A stem cell transplant (bone marrow transplant (BMT)) can cure DBA anemia. This measure is particularly considered in patients who are dependent on transfusions, as frequent transfusions can lead to organ damage. BMT is currently the only form of therapy that can cure DBAs. Finding a suitable bone marrow donor is difficult and the risk of a bone marrow transplant from a non-family donor is so high that such therapy must be decided on a case-by-case basis. A cure by eliminating the cause of the disease is not possible as the cause is not yet known and changes in the chromosomes cannot be reversed. Only in a few cases have spontaneous healing of the Diamond-Blackfan syndrome been described.

See also

Individual evidence

  1. a b c d e Freiburg University Hospital: Diamond Blackfan Anemia - a rare congenital bone marrow disease, accessed on August 7, 2007
  2. ^ LK Diamond, KD Blackfan: Hypoplastic anemia. In: Am. J. Dis. Child. 56/1938, pp. 464-467.
  3. ^ LK Diamond, DW Allen, FB Magill: Congenital (erythroid) hypoplastic anemia: a 25 year study. In: Am. J. Dis. Child. 102/1961, pp. 403-415.
  4. P. Gustavsson et al .: Diamond-Blackfan anemia: genetic homogeneity for a gene on chromosome 19q13 restricted to 1.8 Mb. In: Nat. Genet. 16/1997, pp. 368-371.
  5. P. Gustavsson et al .: Diamond-Blackfan anaemia in a girl with a de novo balanced reciprocal X; 19 translocation. In: J. Med. Genet. 34/1997, pp. 779-782.
  6. N. Draptchinskaia et al .: The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anemia. In: Nat. Genet. 21/1999, pp. 168-175.
  7. H. Gazda et al .: Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease. In: Blood . 97/2001, pp. 2145-2150.
  8. www.diamond-blackfan.de accessed on August 7, 2007
  9. Aase-Smith syndrome at whonamedit.com
  10. Ludwig Heilmeyer , Herbert Begemann: Blood and blood diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition ibid. 1961, pp. 376–449, here: p. 416: The aplastic anemia in the narrower sense (Erythrobladtophthise).
  11. Medical practice: D. Blackfan syndrome ( Memento from September 28, 2007 in the Internet Archive )
  12. A. Vlachos et al: The Diamond Blackfan Anemia Registry: tool for investigating the epidemiology and biology of Diamond-Blackfan anemia. In: J. Pediatr. Hematol. Oncol. 23/2001, pp. 377-382.

literature

  • Friedrich Carl Sitzmann: Pediatrics. (= Dual row). 2nd Edition. Georg Thieme Verlag, Stuttgart 2002, ISBN 3-13-125332-0 , p. 455.

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