Benign familial hematuria (BFH) is a renal disorder characterized by thinning of the renal glomeruli basement membrane from a normal value of 300-400 nm to 150-250 nm. The thinning results in hematuria; however, appearance of blood in urine is microscopic and is normally not visible to the naked eye. Usually, affected individuals maintain normal kidney function, but some patients may show proteinuria (>500 mg/day), and renal impairment. At least 1% of the population worldwide is estimated to be affected by this disorder.
The only way to conclusively diagnose BFH is through a renal biopsy, where the glomerular basement membrane thinning can be visualized. However, in cases with hematuria, BFH is usually diagnosed without taking the aid of biopsies. In such cases, two important disorders have to be considered for differential diagnosis: X-linked Alport syndrome, and IgA nephropathy. Medication is not very important for patients affected with TBMN, since the condition runs a very mild course. Angiotensin converting enzymes may be administered to reduce the episodes of hematuria.
BFH has been found to run in many families in an autosomal dominant fashion. Of these, 40% families have shown disease segregation with Collagen, Type IV, Alpha-3 (COL4A3) and Collagen, Type IV, Alpha-4 (COL4A4) loci. At least 20 mutations in these genes have been identified in affected individuals. Since these are the same genes that are involved in the autosomal dominant form of Alport syndrome, some cases of TBMN may represent the carrier state for the condition. The remaining 60% of familial cases cannot be explained purely by de novo mutation, and therefore, it is strongly felt that other loci are involved. Genetic tests to diagnose BFH are fairly difficult, because of the huge size of the COL4A3 and COL4A4 genes, as well as the possibility of additional loci involved. However, in conditions of hematuria, genetic testing is performed to exclude X-linked Alport syndrome as a possible cause, thereby leaving only BFH as a possible diagnosis.
Both the COL4A4 and COL4A3 genes each encode one of the six subunits of type IV collagen, the major structural component of basement membranes. The genes are organized in a head-to-head conformation with other type IV collagen genes so that each gene pair shares a common promoter.