Table 3.

Distinction between X-linked and autosomal recessive Alport syndrome

CharacteristicX-linked Alport SyndromeAutosomal Recessive Alport Syndrome
PrevalenceMore common, occurs in 85% of all families15% of all families
SexMales are affected more often and more severely than femalesMales and females affected with equal frequency and severity; suspected where a female has renal failure, hearing loss, or ocular abnormalities
Age at first presentationMales have hematuria from infancy, but renal failure occurs typically from the teenage yearsMales and females present with hematuria from infancy and develop renal failure in childhood or adult life
Family history of renal failureOther male relatives may have renal failure; disease appears to “skip” a generation because affected females are much less likely to develop renal failureRenal failure typically found in only one generation. The exceptions are the rare families with multiple examples of consanguinity
Carrier features95% affected females have hematuria and 15% develop renal failure by the age of 60 years; hearing loss and peripheral retinopathy occur in nearly half by age 60 yrCarriers often have hematuria, but renal failure is uncommon, and hearing loss and ocular abnormalities do not occur
Pedigree analysisMother typically has hematuria, and the father has no hematuria, that is, father-to-son disease transmission does not occurHematuria but not renal failure may be present in the mother and father and in other family members.
Lamellated GBMYes, but thinning with focal lamellation in young boys and females becomes more lamellated with timeYes
α3α4α5(IV) collagen chains absent from GBMYesYes, but the α5(IV) chain persists in the Bowman capsule and the distal tubular basement membrane
α5(IV) collagen chain absent from skinYesNo, the α5(IV) chain persists in the skin
Mutation analysisA single pathogenic mutation in the COL4A5 geneTwo pathogenic mutations in the COL4A3 or COL4A4 gene on different chromosomes