Alport syndrome

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Classification according to ICD-10
Q87 Other specified congenital malformation syndromes involving multiple systems
Q87.8 Other specified congenital malformation syndromes, not elsewhere classified
Alport syndrome
ICD-10 online (WHO version 2019)

The Alport syndrome , and hereditary nephritis ( "hereditary nephritis") or progressive hereditary nephritis called, is a hereditary disease with malformed collagen fibers of the type IV. It was first in 1927 by Arthur Cecil Alport described by a British family.

frequency

Alport syndrome is an inherited, chronic progressive nephropathy that can lead to kidney failure. The prevalence is around 1: 7500. 80% of those affected are male.

root cause

To date, over 300 different mutations are known that cause defects in the α chain of type IV collagen, which occurs in the basement membranes of the inner ear , eye and kidney . Depending on the location of the mutation, different inheritance patterns can exist:

  • In 80% of cases is an X-linked - dominant before inheritance. The mutation is on Xq22.3 and affects the gene COL4A5 .
  • At 10%, there is a autosomal - recessive inheritance, the mutation is located on chromosome 2 , locus q35-36. The genes COL4A3 or COL4A4 can be affected .
  • Approx. 10% of the cases are due to new mutations.
  • Alport syndrome is very rarely based on an autosomal dominant inheritance.

Symptoms

Inner ear hearing loss in Alport syndrome

The first symptom is usually hematuria ( blood in the urine ), to which then proteinuria ( protein in the urine) is added. In young adulthood, bilateral inner ear hearing loss occurs in 50% of cases , especially in the frequency range 2000–8000 Hz. In around 10% there are changes in the eyes, mostly due to a cone-shaped protrusion of the eye lens (lenticonus). Other eye diseases include keratoconus , cataracts , as well as changes in the fundus , retinal spots in the macula and the center of the periphery. In the further course, chronic progressive renal insufficiency develops , which usually makes renal replacement therapy necessary at the beginning of the second decade of life .

diagnosis

If there is a positive family history, hearing impairment, and hematuria, Alport's syndrome is suspected. The diagnosis can be confirmed by a kidney biopsy or a molecular genetic examination.

therapy

Until recently, the course of the disease was viewed as fateful, although molecular genetic diagnosis is possible in infancy before the onset of the disease.

Promising study results suggest that preventive therapy with ACE inhibitors can delay the progression of kidney disease by several years. It is assumed that - in addition to the damage to the kidneys caused by Alport's syndrome itself - the high blood pressure caused by renal insufficiency also damages kidney function. It is therefore particularly important to start early blood pressure treatment with low target values ​​(120/80 mmHg).

Despite these promising therapeutic approaches, no causal therapy is currently available. If the kidney failure becomes so severe that, without therapy, threatening uremia would result, dialysis is started . In addition, if necessary, arterial blood pressure should be kept below 130/80 mmHg with ACE inhibitors, as this delays the progression of the disease. Another option is a kidney transplant .

forecast

Because of the X-linked inheritance, men are mainly affected. The course is very variable, but terminal renal insufficiency, which requires dialysis, often occurs in young adulthood.

literature

Individual evidence

  1. ↑ O. Gross, K.-O. Netzer, R. Lambrecht, C. Jung, S. Seibold, A. Leinonen, M. Weber: Meta-analysis of genotype - phenotype correlation in X-linked Alport Syndrome: Impact on genetic counseling. In: Nephrol Dial Transpl. 17, 2002, pp. 1218-1227.
  2. ↑ Chugh KS, Sakhuja V, Agarwal A, Jha V, Joshi K, Datta BN, Gupta A, Gupta KL: Hereditary nephritis (Alport's syndrome) - clinical profile and inheritance in 28 kindreds . In: Nephrology, Dialysis, Transplantation . 8, No. 8, 1993, pp. 690-5. PMID 8414153 .
  3. ^ N. Siegmund-Schultze: In Alport syndrome, ACE inhibitors prolong survival. In: Dtsch Arztebl . Volume 109, Number 18, 2012, pp. A-896 / B-770 / C-766.
  4. ↑ O. Gross, C. Licht et al .: Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. In: Kidney International . Volume 81, Number 5, March 2012, pp. 494-501, ISSN  1523-1755 . doi: 10.1038 / ki.2011.407 . PMID 22166847 .
  5. ↑ J. Temme, F. Peters et al .: Incidence of renal failure and nephroprotection by RAAS inhibition in heterozygous carriers of X-chromosomal and autosomal recessive Alport mutations. In: Kidney International. Volume 81, Number 8, April 2012, pp. 779-783, ISSN  1523-1755 . doi: 10.1038 / ki.2011.452 . PMID 22237748 .

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