Advanced renal insufficiency in a 34-year-old man with Lowe syndrome

Lowe syndrome, or oculocerebrorenal syndrome of Lowe (OCRL), is a rare X-chromosomal disorder characterized by renal dysfunction, congenital cataract, and, in the majority of cases, mental retardation. Although gradual loss of renal function has been seen in most patients, age of onset of deterioration in renal function and its severity and course over time in adult patients have not been documented in detail. We report a 34-year-old man with OCRL without histological changes in renal tissue at the ages of 5 and 8 years, whereas at the age of 29 years, focal and segmental glomerulosclerosis and tubular atrophy were found. During subsequent follow-up of 5 years, progressive loss of renal function occurred, and end-stage renal failure can be expected in a few years. Clinical diagnosis was strongly supported by detecting a nucleotide substitution (IVS19+1g-->a) in the evolutionarily strictly conserved splice consensus sequence of intron 19 of the OCRL1 gene, which may interfere with normal splicing. Clinical course, possible molecular consequences of this novel mutation, and correlation between genotype and phenotype are discussed.