Internal Medicine

  • X-linked disease: Mutation in type 4 collagen leads to an abnormal basement membrane of the kidney, sensorineural hearing loss, and lens abnormalities (lenticonus, corneal dystrophy, macular thinning).
  • Diagnosis: Family history, genetic testing, kidney biopsy showing lamellation of the basement membrane.
  • Management: Supportive only. (Avoid renal transplantation?)
  • Contraindicated: Renal transplantation - resulting Rapid Progressive GN from transplantation



Pediatrics

A group of inherited, heterogeneous disorders involving the basement membranes of the kidney (Type IV collagen).

Clinical Manifestations

Hematuria

  • Most common and earliest manifestation of Alport syndrome

Proteinuria

  • Develops in males with XLAS and in males and females with ARAS and ADAS

Hypertension

  • Usually present in males with XLAS and in males and females with ARAS and ADAS

Sensorineural Deafness

  • Affects 50-90% of individuals

Ocular Manifestations

  • Anterior lenticonus
  • Retinopathy

Alport Syndrome

  • Hereditary nephritis with sensorineural deafness and anterior lenticonus (conical deformity of lens of eye seen with slit-lamp)
  • X-linked (most common) and autosomal recessive forms
  • X-linked – males affected; female carriers all have microscopic hematuria; with lyonization some females may develop hypertension and renal disease, but with milder and later onset
  • Autosomal recessive (chromosome 2) – both sexes equally severe
  • Basic defect is in production of subunits for type IV collagen (two subunits coded for on X chromosome, two on chromosome 2); type IV collagen is located in kidney, eye, and inner ear – hence the main clinical features
  • Presents with incidental finding of microscopic hematuria, or episode of macroscopic hematuria
  • Deafness around 10 years
  • Hypertension in mid-teens
  • Eye signs in mid–late teens (not before 12 years)
  • Average age for end-stage renal failure is 21 years