Disease relevance of Alkaptonuria

• Hereditary tyrosinemia type I and alkaptonuria are disorders of tyrosine catabolism caused by deficiency of fumarylacetoacetate hydrolase (FAH) and homogentisic acid dioxygenase (HGD), respectively [1].
• Five patients with findings consistent with ochronosis, including pigmentary changes of the ear and mild degenerative disease of the spine and large joints, were diagnosed clinically as having alkaptonuria, but the diagnosis was withdrawn based on normal urine HGA levels [2].
• Some disorders, in particular oxalosis, may involve the conduction system as a result of the deposition of oxalate crystals and result in conduction disturbances such as in alkaptonuria, primary oxalosis, and homocystinuria [3].
• We present a case of alkaptonuria which resulted in aortic stenosis and coronary artery disease due to homogentisic acid deposition [4].
• Eight of 10 subjects suffering from alkaptonuria, with or without ochronotic arthropathy or spondylosis, had B27 [5].

High impact information on Alkaptonuria

• Alkaptonuria is a rare metabolic disorder resulting from loss of homogentisate 1,2 dioxygenase (HGO) activity [6].
• Coinheritance of either neonatal severe hyperparathyroidism or sucrase-isomaltase deficiency and alkaptonuria provided a candidate location for the mutated genes on chromosome 3 [7].
• Analysis of two additional nonconsanguineous families supports linkage of alkaptonuria to this single locus (combined lod score = 4.3, theta = 0) [7].
• Alkaptonuria (AKU), a rare hereditary disorder of phenylalanine and tyrosine catabolism, was the first disease to be interpreted as an inborn error of metabolism [8].
• The diagnosis of alkaptonuria was confirmed or ruled out by measurement of HGA in the urine [2].

Chemical compound and disease context of Alkaptonuria

• Analysis of a class of these mutations demonstrates that loss of homogentisate dioxygenase (leading to alkaptonuria in humans) prevents the effects of a Fah deficiency [9].
• This could be of increased significance now that minocycline and other tetracyclines have been proposed as therapeutic options for rheumatoid arthritis, bringing a new population of patients with ochronosis and arthritis to medical attention with the potential, but incorrect, diagnosis of alkaptonuria [2].
• Interference in urine oxalate assay (sigma diagnostics oxalate oxidase method) from homogentisic acid in alkaptonuria [10].
• Effects of ascorbic acid in alkaptonuria: alterations in benzoquinone acetic acid and an ontogenic effect in infancy [11].
• Alkaptonuria (AKU; McKusick No. 203500), a rare hereditary disorder of the phenylalanine catabolism, was the first disease to be interpreted as an inborn error of metabolism (A. E. Garrod, 1902, Lancet 2: 1616-1620) [12].

Anatomical context of Alkaptonuria

• The deficiency of homogentisic acid oxidase, an enzyme that is mainly found in hepatocytes, is associated with alkaptonuria and ochronosis [13].

Gene context of Alkaptonuria

• Cloning of the homogentisate 1,2-dioxygenase gene, the key enzyme of alkaptonuria in mouse [14].
• Nitisinone, an inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase, can drastically reduce urinary excretion of HGA in individuals with alkaptonuria [15].

Analytical, diagnostic and therapeutic context of Alkaptonuria

• Sequence analysis of the homogentisate 1,2 dioxygenase gene in a family affected by alkaptonuria [16].
• To detect and follow-up the metabolic status of patients with alkaptonuria (AKU), urinary homogentisic acid (HGA) was measured by gas chromatography [17].
• Diagnosis of alkaptonuria by NMR urinalysis: rapid qualitative and quantitative analysis of homogentisic acid [18].

References