Rare Diseases - Alport syndrome

The key features of this inherited cause of kidney failure are summarised by Dr Raj Thakkar.

What is it?

  • Alport syndrome is a rare inherited disorder, which can lead to nephritis and deafness.
  • It accounts for around one in 500 cases of end-stage renal failure.

Who is at risk?

  • X-linked Alport syndrome is the most common genetic anomaly. However, a number of different genetic abnormalities have been identified, all of which cause type IV collagen defects.
  • An abnormal glomerular basement membrane secondary to the collagen defect underpins the renal component of the disease.
  • Males are more seriously affected than females in X-linked disease, while males and females are affected equally in autosomal dominant or recessive disease. Carriers may also be symptomatic, albeit mildly. This article relates mainly to X-linked Alport syndrome.

How does it manifest?

  • Alport syndrome is a progressive disease that often presents with haematuria in early childhood.
  • Frank haematuria may be precipitated by respiratory tract infections. The absence of haematuria has a good negative predictive value for Alport syndrome.
  • Proteinuria tends to present later in life and may progress to nephrotic range. Renal hypertension complicates Alport syndrome.
  • About nine in 10 patients progress to end-stage renal failure by their fifties. Risk of progression depends on a number of factors, including the genetic mutation underlying the disease.Renal failure is far more significant in males with X-linked Alport syndrome.
  • Hearing and visual disturbance usually presents in childhood or in early teens. Sensorineural deafness affects most patients. Hearing loss pre-dates renal failure.
  • Ocular manifestations include lenticonus and retinopathy. Other complications include oesophageal and pulmonary leiomyomas, which may cause pain, dysphagia, vomiting, cough, breathlessness and stridor.
  • Some subtypes of Alport syndrome cause bleeding problems secondary to platelet dysfunction and megathrombocytopenia on their blood film. White cell abnormalities may be found.

How is it managed?

  • Patients who progress to end-stage renal failure do well with renal transplantation. In a small minority, the transplanted kidney may develop anti-glomerular basement membrane disease, which destroys the transplant.
  • ACE inhibitors may delay progression to renal failure and help to control hypertension.
  • Surgical, ENT and ophthalmic intervention may be required for complications.
Dr Thakkar is a GP in Wooburn Green, Buckinghamshire

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