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