Alkaptonuria is a rare inherited genetic disorder of phenylalanine and tyrosine metabolism. This is an autosomal recessive condition that is caused due to a defect in the enzyme homogentisate 1,2-dioxygenase, which participates in the degradation of tyrosine. As a result, homogentisic acid and its oxide accumulate in the blood and are excreted in urine in large amounts. The polymer of homogentisic acid called alkapton impregnates bradotrophic tissues.
The article summarizes data on the association of Klinefelter syndrome (KS) with autoimmune rheumatic diseases, that is rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), polymyositis/dermatomyositis, systemic sclerosis (SSc), mixed connective tissue diseases (MCTD), Sjogren’s syndrome and antiphospholipid syndrome (APS). Recently, a higher risk for RA, SLE and Sjogren’s syndrome in patients with KS has been clearly demonstrated. However, the association of other autoimmune rheumatic disorders such as dermatomyositis/polymyositis, SSc, MCTD and APS is reported only casually. Based on the hormonal changes in KS, there are suggestions that low androgen and higher estrogen levels might be a predisposing factor for the development of autoimmune diseases, but evidence for the association is poor. Epidemiologic studies on larger cohorts of patients are required.