CASE REPORT Five Cases of Alkaptonuria Among Two Generations of Single Family in Dharwad, Karnataka (India) Dhiraj J. Trivedi • Vikram Haridas Received: 13 February 2015 / Accepted: 15 February 2015 Ó Association of Clinical Biochemists of India 2015 Abstract Alkaptonuria (AKU) is a disorder of tyrosine metabolism. A rare disorder due to accumulation of ho- mogentisic acid leading to progressive deposition of grey to bluish black pigment causing degenerative changes in car- tilage. Medical interest of AKU is due to medical triad arthropathy, Ochronosis and Homogentisic aciduria. A 38  years old male presented with complain of back pain, which persisted since last 8 months. Hyper-pigmentation of skin of chick, discolouration on ear cartilage and pigmentation of the conjunctiva on both eyes were observed. X-ray findings were normal except inter-vertebral disc calcification. Based on the results obtained from Clinical examination, X-ray findings and Biochemical investigations, diagnosis was confirmed as AKU. On screening family members additional four persons have been detected positive but, without any clinical symptoms. AKU, though rare it may occur in cluster among the family members. Keywords Alkaptonuria Á Ochronosis Á Homogentisic acid Á Black urine Á Tyrosine Introduction Alkaptonuria (AKU) is a rare, autosomal, recessively in- herited inborn error of phenylalanine and tyrosine metabolism. Congenital deficiency or mutation [1] of Homogentisate 1,2-dioxygenase enzyme [EC.1.13.11.5] is responsible for defective metabolism of tyrosine. Homogentisic acid (HGA) produced as intermediate in this metabolism is not further oxidised to maleyl acetoacetate. As a result levels of HGA increases in the blood and ex- creted in urine. Oxidation of HGA in alkaline medium develops black colour with in 10 min. In body HGA is converted to Benzoquinone acetic acid which is deposited in connective and cartilaginous tissue imparting bluish black pigmentation. Because AKU is so rare it is unknown to general public and overlooked by many clinicians. Prevalence of 1 in 250,000 to 1 in 500,000 live births has been reported from UK and US population. However, higher incidences of 19–25 in 500,000 live births are reported from Slovakia, Dominican Republic and Middle East countries [2]. Though there is lack of such systemic survey, few scattered cases have been reported from various parts of India [3–8]. Dark black pigmentation in diapers can be indicative of disorder in infancy but, probably due to lack of public health education among common Indian it remains unno- ticed or ignored and remains asymptomatic. It becomes apparent at about fourth decade of life when arthritic complication sets in. Though AKU is not life threatening disorder, it is important in diagnosis of arthritis of unknown cause. Provisional diagnosis is based on the clinical fea- tures (arthritis and/or Ochronosis) and change of urine colour on standing due to Homogentisic aciduria. This can be confirmed by simple biochemical tests like, making the pH of urine alkaline by adding NaOH, Ammonical AgNO 3 reduction test, Benedict’s test, Ferric Chloride test or quantitative measurement of HGA in urine by gas chro- matography or mass spectrophotometer [9, 10]. D. J. Trivedi (&) Department of Biochemistry, SDM College of Medical Sciences and Hospital, Dharwad, Karnataka, India e-mail: dhiraj99trivedi@gmail.com V. Haridas Department of Rheumatology, SDM College of Medical Sciences and Hospital, Dharwad, Karnataka, India e-mail: haridasvikram@yahoo.co.in 123 Ind J Clin Biochem DOI 10.1007/s12291-015-0488-y