Alkaptonuria

Excerpt

Alkaptonuria is one of a rare autosomal recessive genetic disorder, which results from the deficiency of homogentisate 1,2 dioxygenase (HGD). HGD gene is expressed in the liver, kidney, prostate, small intestine, and colon. This enzyme plays a role in the metabolism of tyrosine that converts homogentisic acid (HGA) into malate and acetoacetate. In the absence of HGD, homogentisic acid produced in excess by the liver oxidizes into ochronotic pigment polymer. Accumulation of this pigment in various tissues leads to systemic disease. This process is called ochronosis.

Alkaptonuria was amongst the first genetic disorders in humans that found to follow the principles of Mendelian recessive inheritance. Historically, in 1908 it was used by Archibald Garrod in his Croonian lectures to illustrate the principles behind "inborn errors of metabolism." However, the Egyptian mummy Harwa believed to be the first clinical case of Alkaptonuria dating back as far as 1500 BC. The term alkaptonuria originated from the Arabic word "alkali." Also, Boedeker created the name in 1859 after he noticed unusual decreasing properties in patient urine. In 1866 ochronosis was discovered by Virchow, who noticed under microscopy when HGA pigment appeared to be a pale brownish yellow color (ochre-like).