Overview of Alport syndrome: Hereditery Nephritis with Sensorineural deafness

This is a case of 17 Years old Malay students who is the youngest out of four siblings and the product of non consangious marriage. He was admitted through pediatric clinic because of symptomatic anemia and upper respiratory tract infection.

Patient is a known case of bronchial asthma and on two types of medication which are symbicort turbohaler 2 puff b.d and Bricanyl turbohaler 2 puff daily.

He was also diagnosed as Alport’s syndrome since last year after admitted with symptomatic uremia, bilateral sensorineural hearing loss and was undergone hemodialysis.

Discussion

Alport syndrome is a group of heterogeneous inherited disorder affecting basement membrane of kidney, cochlea and eyes as a result of mutation in type IV collagen genes. It is inherited via X-linked in 80% of the patient, autosomal recessive in 15% and autosomal dominant in 5% of patient diagnosed as Alport syndrome.

The mutations are located in the COL4A5 gene encoding the α5 chain of type-IV collagen. Autosomal Alport syndrome is caused by mutations in the COL4A3 and COL4A4 genes encoding the α3 and α4 chain of type-IV collagen.

Alport has proposed this disease as a combination of progressive hereditary nephritis with sensorineural deafness in 1927.

The presence of three out of four proposed diagnostic criteria establish the diagnosis of Alport syndromes which are; 1) Family history of hematuria, progressing mostly in males to end-stage renal disease (ESRD), 2)Thickening and splitting of the glomerular basement membrane detected by electron microscopy, 3) Progressive, high-frequency, sensorineural deafness and 4) Anterior lenticonus and perimacular flecks

Hasstedt et al have recently proposed that there are six types of dominant AS. Type 1 is the classical juvenile AS with deafness. This is an interim designation for families where affected males had no offspring. Type II is the proven X-linked juvenile AS with deafness. Type III is the X-linked adult AS with deafness. Type IV is the X-linked adult AS without deafness or other defects. Type V is the autosomal AS with deafness and thrombocytopathia, and type VI is the autosomal juvenile AS with deafness. There may also be a type VII, which concerns the recessive autosomal form of inheritance. [J. Feingold and E. Bois]

Renal manifestation includes hematuria, proteinuria and hypertension.

Sensorineural deafness is a characteristic feature observed frequently. Some of them may have severe nephropathy but normal hearing. This problem is never present at birth and usually apparent by late childhood or early adolescence, generally before the onset of renal failure. Hearing impairment is always associated with renal involvement.

Ocular manifestations include anterior lenticonus, Dot-and-fleck retinopathy and posterior polymorphous.

Male patients with the typical X-linked disease have a renal half-life of about 25 years, and about 90% develop ESRD before 40 years of age. In female patients, observations have shown that as many as 12% of female patients also develop ESRD by age 40 years; this rate increases to 30% by age 60 years and 40% by age 80 years. [Prasad Devarajan]

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Reference

1) J. Feingold and E. Bois, "Genetics of Alport's syndrome", Pediatr Nephrol (1987) 1 : 436-438

2) Prasad Devarajan, "Alport Syndrome", http://emedicine.medscape.com/article/981126-overview

3) Ramesh Saxena, "Alport Syndrome", http://emedicine.medscape.com/article/238260-overview