Bartter syndrome

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Classification according to ICD-10
E26.8 Other hyperaldosteronism
- Bartter syndrome
ICD-10 online (WHO version 2019)

The Bartter syndrome is an extremely rare inherited disease of the ascending branch of the loop of Henle in the kidney with salt-wasting syndrome, hypokalemic metabolic alkalosis and secondary hyperaldosteronism with normal or low blood pressure. In addition to the classic form, there is an antenatal form of the unborn fetus with polyhydramnios . These are tubulopathies . Renal failure does not occur .

description

There is a defect in the furosemide- sensitive Na + / K + / 2Cl - cotransporter (NKCC2, type I; also called BSC1) [or the apical K + channel ( ROMK ; type II) or the basolateral Cl - channel ( CLCKB, type III), which cooperate with Na + / K + / 2Cl - cotransport during the resorption of NaCl in the dilution segment ] in the ascending branch of Henle's loop of the kidney. As a result, sodium ions cannot be reabsorbed enough, which means that blood pressure drops. On the one hand, this leads to the release of catecholamines via pressoreceptors in the aorta and, on the other hand, because of the reduced blood flow to the vasa afferentia, to a release of renin and hyperreninemic hyperaldosteronism .

Type IV is characterized by a defect in Barttin, the essential β subunit of the ClC-K-channel except in the basolateral membrane of the loop of Henle in the basolateral membrane of the stria vascularis in the inner ear expressed is. This phenotype shows an additional deafness because the production of the K + -rich endolyphe is inhibited.

Type V has a mutation in the CaSR (extracellular calcium ion sensing receptor) that inhibits NKCC2 and ROMK.

Hyperprostaglandin E syndrome is a combination of types I, II and III.

frequency

The disease is very rare with a probability ( prevalence ) of 1 to 9: 1,000,000.

genetics

Types I to IV inheritance is autosomal - recessive . Type V is, however autosomal - dominant inherited.

So far, five different genes have been found that are involved in the development of Bartter syndrome:

Bartter syndrome Chromosome gene locus gene encoded protein
Type I. Chromosome 15q15-q21.1 SLC12A1 NKCC2
Type II Chromosome 11q21-25 KCNJ1 ROMK
Type III Chromosome 1p36 ClCNKb ClCN-Kb
Type IV Chromosome 1p31 BSND Bartender
Type V Chromosome 3q13.3-q21 CASR CaR

Symptoms

The blood pressure is typically despite increased renin and aldosterone decreased. With low potassium levels, metabolic alkalosis and salt loss occur. Dehydration , vomiting, and polyuria are possible. As a result of hyperaldosteronism , hypokalemia and metabolic alkalosis develop .

Other symptoms are:

Differential diagnosis of urinary concentration disorders

Bartter syndrome Schwartz-Bartter Syndrome Diabetes insipidus centralis Diabetes insipidus renalis
Pathophysiology Channel defect in the kidney
(Na + / K + / 2Cl - -Symporter, ROMK or CLCKB )		 Inappropriately high ADH secretion
→ incorporation of aquaporins ↑		 Insufficient ADH secretion
→ incorporation of aquaporins ↓		 ADH type 2 receptor defect
→ aquaporin incorporation ↓ or aquaporin defect
etiology hereditary (autosomal recessive)
  1. paraneoplastic (small cell lung cancer )
  2. secondary to infections or CNS disorders
  1. idiopathic (approx. 1/3 of the cases)
  2. secondary in tumors, after trauma, in infections
  1. hereditary (X-linked or autosomal recessive)
  2. acquired in kidney disease
clinic Salt appetite, muscle weakness and muscle pain , cramps CNS symptoms , muscle weakness and pain , cramps increased amount of urine , increased amount of drink increased amount of urine , increased amount of drink
laboratory Serum: Na + ↓, K + ↓, osmolality ↓, pH value ↑ Serum: ADH ↑, Na + ↓, K + ↓, osmolality ↓, pH value ↑ Serum: ADH ↓, Na + ↑, osmolality ↑ Serum: ADH ↔, Na + ↑, osmolality ↑
Urine: Na + ↑, K + ↑, osmolality ↑ Urine: Na + ↑, osmolality ↑ Urine: Na + ↓, osmolality ↓ Urine: Na + ↓, osmolality ↓
Further diagnostics Evidence of secondary aldosteronism
  1. Thirst test: ADH ↔
  2. Desmopressin test: urine osmolality ↑
  1. Thirst test: ADH ↑
  2. Desmopressin test: urine osmolality ↔

therapy

Attempts are made to raise potassium and sodium levels through infusions. In addition, aldosterone antagonists and prostaglandin synthesis inhibitors (e.g. indomethacin ) can be used.

Antenatal Bartter Syndrome

The antenatal Bartter syndrome is also usually inherited as an autosomal recessive trait. The same loss-of-function mutations were described as for the classic form. The loss of salt in the thick ascending branch of the Henle loop leads to massive polyuria and severe polyhydramnios in utero , which usually lead to premature birth . The treatment mainly includes a fluid balance and a salt supplement in each case antepartally for the pregnant woman . Nonsteroidal anti-inflammatory drugs are in neonates due to the possibility of serious adverse events in the postpartum ( postnatal only used with caution). A postpartum treatment of the mother is not required.

In addition, a Marburg working group described in 2016 a transient form of the antenatal Bartter syndrome with an X-linked inheritance , triggered by a mutation of the gene for the "melanoma-associated antigen D2" (MAGE-D2) in the area Xp11.2 . The exact molecular function of this protein is not known. It binds to the chaperone Hsp-40 and to the cytoplasmic Gs-alpha protein and is involved in cell cycle regulation, apoptosis and neurogenesis . It is also associated with some cancers . The main clinical implication is that the high-risk postnatal therapy of Bartter syndrome is not necessary.

history

Bartter syndrome was first described in 1962 by the American endocrinologist Frederic Bartter (1914-1983).

See also

References and footnotes

  1. ↑ orpha.net: Bartter Syndrome
  2. ↑ a b G. Colussi: Bartter syndrome. In: Orphanet encyclopedia. March 2005.
  3. ↑ SLC12A1 = Solute carrier family 12 sodium / potassium / chloride transporters, member 1
  4. ↑ Gerd Herold : Internal Medicine . Cologne 2007, p. 564-565, 712-713 .
  5. ↑ Kamel Laghmani, Bodo B. Beck, Sung-Sen Yang, Elie Seaayfan, Andrea Wenzel, Björn Reusch, Helga Vitzthum, Dario Priem, Sylvie Demaretz, Klasien Bergmann, Leonie K. Duin, Heike Göbel, Christoph Mache, Holger Thiele, Malte P. Bartram, Carlos Dombret, Janine Altmüller, Peter Nürnberg, Thomas Benzing, Elena Levtchenko, Hannsjörg W. Seyberth, Günter Klaus, Gökhan Yigit, Shih-Hua Lin, Albert Timmer, Tom J. de Koning, Sicco A. Scherjon, Karl P. Schlingmann, Mathieu JM Bertrand, Markus M. Rinschen, Olivier de Backer, Martin Konrad, Martin Kömhoff: Polyhydramnios, Transient Antenatal Bartter's Syndrome, and MAGED2 Mutations . The New England Journal of Medicine 2016, Volume 374, Issue 19, May 12, 2016, Pages 1853–1863, DOI: 10.1056 / NEJMoa1507629
  6. ↑ Nine VAM Knoers, René J. Bindels: MAGE-D2 and the Regulation of Renal Salt transporter . The New England Journal of Medicine 2016, Volume 374, Issue 19, May 12, 2016, pages 1888-1890, DOI: 10.1056 / NEJMe1603856
  7. ↑ Frederic C. Bartter u. a .: Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis: a new syndrome. In: Am. J. Med. 33/1962, pp. 811-828. PMID 13969763

literature

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