A 40 yr old woman presents with progressive palmoplantar pigmentation. X-ray spine shows calcification of interveebral discs. On adding Benedict's reagent to urine, it gives greenish brown precipitate and blue-black supernatant fluid. What is the diagnosis?
Alkaptonuria Age of patient, calcification of interveebral disc, pigmentation and reaction with Benedict's reagent give away the diagnosis of Alkaptonuria. All the options mentioned in this question are inherited disorders of amino acid metabolism. Phenylketonuria, tyrosinemia type 2 and Arigininosuccinic aciduria present during infancy or childhood, whereas Alkaptonuria presents usually at 40 yrs of age. It may go unrecognized until middle life. Mental retardation is usually seen in all the other 3 options. (Mental retardation not seen in Alkaptonuria). Alkaptonuria Triad of: - Homogentisic aciduria - Black pigmentation of cailage and collagenous tissue (ochronosis) - Ochronotic ahritis It is a rare autosomal recessive disorder of tyrosine catabolism. There is deficiency of homogentisic acid oxidase which results in the accumulation of homogentisic acid pigment cailages and collagenous tissues (ochronosis). Large amount of homogentisic acid is excreted in urine which gets oxidised on exposure to air and impas urine a dark colour especially if the pH of urine is alkaline. Alkaptonuria is usually recognised by 30-40 yrs of age when degenerative joint disease and ochronosis (pigmentation) become noticeable. Ochronosis ahritis commonly involves shoulder, hips and knees. The interveebral discs are degenerated, spaces are narrowed and calcification occurs. Ochronosis or pigmentation can involve- hea valves, larynx, tympanic membrane, sclera, ear cailage and skin. Occasionally pigmented renal or prostatic calculi can occur. Homogentisic acid (HGA) is a strong reducing agent and gives positive reaction with Benedict's & Fehling's reagent. A greenish brown precipitate with brownish black supernatant develops with Benedict's reagent and transient blue green colour develops with Fehling's (FeC13) reagent. The diagnosis is confirmed by measurement of HGA concentration in urine by paper and thin layer chromatography. Low protein diet especially low in phenylalanine and tyrosine is advocated in combination with ascorbic acid, but not very effective. Addition of nitisinone (an inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase which catalyzes the formation of homogentisic acid) drastically reduces urinary excretion of homogentisic acid might prevent the long term complication of alkaptonuria.
Phenylketonuria
Alkaptonuria
Tyrosinemia type-2
Argininosuccinic aciduria