Alport's syndrome

Fifty-eight children with Alport's syndrome which were investigated and followed up in our department during the last 20 years are reported in this study. Forty-two were male and 16 female. Age at diagnosis was less than six years in 74 percent of them. All had microscopic hematuria, with episodes of gross hematuria in 32 of 58. Proteinuria was an inconstant but frequent finding. Steadily increasing proteinuria, with or without occurrence of the nephrotic syndrome, suggested poor prognosis. Terminal renal failure developed in 18 boys between eight and 25 years of age and in two girls 18 and 24 years old. Hearing impairment was observed in 37 patients and was discovered between five and 15 years of age. Ocular abnormalities, lenticonus anterior and/or macular changes were present in 18 children. Megathrombocytopenia was observed in one child. Forty-two renal specimens from 35 patients were examined by light microscopy and four grades of severity of lesions were distinguished. A good correlation could be established with regard to histologic pattern, age and clinical status at the time of renal biopsy. Ultrastructural study, performed in 20 children one to 17 years old, showed two types of glomerular basement membrane changes: (1) in all cases, diffuse (one case) or focal thickening and splitting of the glomerular basement membrane; (2) in 19 cases, focal thinning of the glomerular basement membrane. Thin and irregular glomerular basement membrane was the predominant feature in younger children. In others, the most impressive change was the irregular alternation of thick, thin and normal glomerular basement membrane. In correlation with the finding of abnormally thin glomerular basement membrane in children recent immunologie and biochemical evidence may suggest that Alport's syndrome could be due to the abnormal persistence of fetal or neonatal glomerular basement membrane.