ABSTRACT
In some patients the diagnosis is suggested by a positive test for urinary-reducing substance, a feature that was also
recognized in 1859 [4]. The urine does not contain glucose, and so laboratories that test urine only with glucose oxidase will miss this opportunity to find alkaptonuria. Homogentisic acid reduces the silver in a photographic emulsion, and alkaptonuric urine may be used to develop a photograph, providing a dramatic qualitative and even quantitative test for the disease
[15,16]. Homogentisic acid may be identified by paper chromatography, and there is a specific enzymatic analysis that permits quantification [17]. We more often find it first on analysis of the urine for organic acids [18], and we have developed an high performance liquid chromatography (HPLC) method for the quantitation of homogentisic acid and
Phenylalanine Phenylketonuria
Melanin
3,4-Dihydroxyphenylalanine (DOPA)
Alkaptonuria
CO2
Tyrosine Albinism (Melanocyte)
Fumaric acid
HOOCC H
CCOOH H
Acetoacetic acid
CH3CCH2COOH
O
Maleylacetoacetic acid
O
C
CH2 CH2HC
HC
COOH
COOHC
Fumarylacetoacetic acid
HOOC
C
CH2 CH2C H
H C COOHC
NH2
CH2CHCOOH
P-Hydroxyphenylpyruvic acid
O
CH2CCOOHHO
Homogentisic acid (2,5-Dihydroxyphenylacetic acid)
OH
CH2COOH
HO
O OO
HO
HO CH2CHCOOH
NH2
HO CH2CHCOOH
NH2
its products [19]. An adult with alkaptonuria excretes as much as 4-8 g of homogentisic acid daily [20]. The compound is excreted so efficiently that little is found in the plasma, although the amounts found by stable isotope internal standard gas chromatography mass spectrometry are considerably higher than those of normal plasma [21].
