Alport’s syndrome

Alport’s syndrome is a genetic condition characterised by renal dysfunction, hearing loss, and eye abnormalities.

It is a rare disease occurring in approximately 1 in 50 000 newborns, and accounts for about 0.6 % of patients with end stage renal disease (ESRD). Hematuria is usually the first symptom, discovered already during the first years of life in males with Alport’s syndrome. The syndrome is a progressive disease and the prognosis depends on type of inheritance, gender, and type of mutation. The genes affected are encoding alpha-3, alpha-4 or alpha-5 chains of type IV collagen of the basement membrane. Three genetic forms of Alport syndrome exist. The most common form, accounting for about 80% of the cases, is X-linked inherited mutation of the alpha chain 5 (XLAS). The two other forms of Alport syndrome are autosomal recessive (ARAS) and autosomal dominant (ADAS). Both conditions involve mutations of the genes for alpha-3 or alpha-4 chains of collagen IV, which are both located on chromosome 2.

Although the glomerular basement membrane (GBM) looks normal in childhood, due to predominance of alpha-1 and alpha 2 chains, it deteriorates with time because of an isotype switching to alpha-3, alpha-4 and alpha-5 chains of type IV collagen. These three chains combine to form a unique collagen network. Structural abnormality of any of these chains limits formation of functional collagen network and prevents incorporation of the other collagen chains. Patients with Alport’s syndrome experience progressive loss of kidney function which can lead to end-stage renal disease at an early age. In men, the symptoms are more severe and get worse faster and approximately 90% develop ESRD by the age of 40. In women, the XLAS disorder is usually mild, with minimal or no symptoms. The probability of reaching ESRD by the age of 40 is about 12%. 

Relevant Literature

  1. Kashtan C. Alport Syndrome and skin basement membrane disease, Curr Diagn Path 8, 349-360, 2002.
  2. Gubler MC et al. Autosomal recessive Alport syndrome: immunohistochemical study of type IV collagen chain distributionKidney Int. 47:1142-1147, 1995.
  3. Kashtan C. Alport Syndrome: Is diagnosis only skin deep? Kidney Int 55, 1575-1576,1999.
  4. Piron Y. Making the diagnosis of Alport´s Syndrome, Kidney Int 56, 760-775, 1999.
  5. Martin P. Type IV collagen. Characterization of the COL4A5 gene, mutations in Alport syndrome, and autoantibodies in Alport and Goodpasture syndromes. PhD Thesis Oulu University, Finland, 2000