Distinction between X-linked and autosomal recessive Alport syndrome
| Characteristic | X-linked Alport Syndrome | Autosomal Recessive Alport Syndrome |
|---|---|---|
| Prevalence | More common, occurs in 85% of all families | 15% of all families |
| Sex | Males are affected more often and more severely than females | Males and females affected with equal frequency and severity; suspected where a female has renal failure, hearing loss, or ocular abnormalities |
| Age at first presentation | Males have hematuria from infancy, but renal failure occurs typically from the teenage years | Males and females present with hematuria from infancy and develop renal failure in childhood or adult life |
| Family history of renal failure | Other male relatives may have renal failure; disease appears to “skip” a generation because affected females are much less likely to develop renal failure | Renal failure typically found in only one generation. The exceptions are the rare families with multiple examples of consanguinity |
| Carrier features | 95% 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 yr | Carriers often have hematuria, but renal failure is uncommon, and hearing loss and ocular abnormalities do not occur |
| Pedigree analysis | Mother typically has hematuria, and the father has no hematuria, that is, father-to-son disease transmission does not occur | Hematuria but not renal failure may be present in the mother and father and in other family members. |
| Lamellated GBM | Yes, but thinning with focal lamellation in young boys and females becomes more lamellated with time | Yes |
| α3α4α5(IV) collagen chains absent from GBM | Yes | Yes, but the α5(IV) chain persists in the Bowman capsule and the distal tubular basement membrane |
| α5(IV) collagen chain absent from skin | Yes | No, the α5(IV) chain persists in the skin |
| Mutation analysis | A single pathogenic mutation in the COL4A5 gene | Two pathogenic mutations in the COL4A3 or COL4A4 gene on different chromosomes |