A patient complains of knee pain, on and off, occasionally associated with knee swelling. On probing fuher, a history of urine turning black on standing is obtained. Routine investigations are unremarkable. What could be the enzyme involved?
Alkaptonuria Autosomal recessive disorder caused by a deficiency of homogentisate 1,2-dioxigenase Large amounts of homogentisic acid are formed which are excreted in urine or deposited in tissues Clinical manifestations The only sign in children is blackening of urine on standing, caused by oxidation & polymerization of homogentisic acid. Ochronosis: Dark spots on the sclera or ear cailage resulting from accumulation of the black polymer of homogentisic acid (Alkapton bodies) Ochronotic Ahritis & ahralgia involves the spine and large joints (shoulders, hips, and knees); can be disabling with advancing age. It High incidence of hea disease (mitral and aoic valvulitis, calcification of hea valves, myocardial infarction Investigation findings: Radiologic findings a narrowing of joint spaces & calcification of interveebral disks Diagnosis is confirmed by finding massive excretion of homogentisic acid on urine organic acid testing. Treatment: Treatment of ahritis is symptomatic. Nitisinone efficiently reduces homogentisic acid production in alkaptonuria. Phenylalanine and Tyrosine-restricted diet may play a role.
Homogentisate oxidase
Xanthine oxidase
Methyl malonate oxidase
Phenyl pyruvate oxidase
Paediatrics