The possibility that infants with urine abnormalities may have both Alport syndrome (AS) and Klinefelter syndrome (KS) should be considered, even they have no family history of the diseases, researchers suggested in a case of a 9-month-old boy.
According to the authors, this is the first case of AS and KS being diagnosed in infancy — and the combination is very rare.
The boy first came to the hospital at 6 months old, following a urinary screening held at his nursery school that detected small amounts of blood and protein in his urine. He had already been diagnosed with KS, a genetic condition characterized by the presence of two X and one Y chromosome which often causes infertility.
A kidney biopsy showed minor abnormalities in the glomeruli (the network of capillary blood vessels) of his kidneys. Further tests made it clear that the alpha-5 chain of type IV collagen was completely absent in his kidneys, a typical manifestation of AS.
The researchers then performed a genetic analysis, and found a new mutation in the COL4A5 gene, which is situated on the X-chromosome, that previously was not associated with AS. Urinary tests of the boy’s elder brother and parents were normal.
A genetic analysis also found that the father had normal male characteristics, with one X and one Y chromosome. No mutations were detected in COL4A5 in blood samples obtained from either parent.
Researchers concluded that the boy’s condition was the result of a newly identified mutation, and he was diagnosed with AS combined with KS. Treatment with Avapro (irbesartan), an angiotensin receptor inhibitor, was begun to delay kidney disease progression.
The probability of AS and KS occurring at the same time by chance is calculated at 1 in 5 million. The researchers identified only two other cases of combined AS and KS in published studies, that of a t-year-old boy and a 31-year-old man. Further studies are needed to clarify any possible relationship between these two diseases.