The Human Gene for Alkaptonuria (AKU) Maps to Chromosome 3q

Janocha, S.; Wolz, Werner; Srsen, S; Srsnová, K; Montagutelli, Xavier; Guénet, Jean-Louis; Grimm, Tiemo; Kreß, Wolfram; Müller, C. R.

doi:10.1006/geno.1994.1003

Cited by 92 publications

(66 citation statements)

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“…14 The human HGO gene locus has been mapped to chromosome 3q21-q23. 2,15,16 In the last decade the HGO gene has been cloned, characterized, and its promoter region identified. 17,18 A total of 84 mutations impairing this enzyme have been found in the HGO gene from humans and model organisms, and 43 of these mutations result in single amino acid substitutions.…”

Section: Discussionmentioning

confidence: 99%

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Alkaptonuric Ochronosis with Aortic Valve and Joint Replacements and Femoral Fracture: A Case Report and Literature Review

Fisher¹,

Davis²

2004

Clinical Medicine & Research

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Alkaptonuria is a rare autosomal recessive disorder of metabolism caused by deficiency of homogentisic acid oxidase and resulting in accumulation of homogentisic acid in collagenous structures. It is characterized by homogentisic aciduria, bluish-black discoloration of connective tissues (ochronosis) and arthropathy of large joints. Less common manifestations include cardiovascular abnormalities, renal, urethral and prostate calculi. Bone fractures are unusual in ochronosis.In this report, we describe a woman, 69 years of age, with a history of dark urine since childhood and progressive pigmentation of the skin, sclera, and auricular cartilages. She had severe arthropathy requiring total joint replacement in both of her knees and right hip. She also had severe aortic stenosis requiring valve replacement, and asymptomatic nephrolithiasis. She presented with a low trauma fracture of the distal femur despite two years of alendroate therapy.We review the etiology, pathogenesis, clinical presentation, diagnosis and treatment of alkaptonuric ochronosis. Early detection is important for prevention and treatment of multiple systems. Nitisinone, a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase, dramatically reduces production and urinary excretion of homogentisic acid; however, the long-term efficacy and side effects of such therapy are unknown. Identifying the gene for alkaptonuria offers the potential for a new therapeutic approach (replacement therapy with a recombinant enzyme) in the treatment of alkaptonuric ochronosis.

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Section: Discussionmentioning

confidence: 99%

“…Alkaptonuria affects between 1 in 250,000 to 1 in 1,000,000 people, [1][2][3] although in some areas such as Slovakia and the Dominican Republic, the incidence is much higher (e.g., up to 1 in 19,000 in Slovakia 4 ).…”

Section: Introductionmentioning

confidence: 99%

Alkaptonuric Ochronosis with Aortic Valve and Joint Replacements and Femoral Fracture: A Case Report and Literature Review

Fisher¹,

Davis²

2004

Clinical Medicine & Research

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“…26 Janocha et al 28 demonstrated linkage to microsatellite markers from proximal 3q. Markers on that chromosome were selected for study because of previously demonstrated homology of synteny with mouse chromosome 16.…”

Section: 23mentioning

confidence: 99%

Alkaptonuria: Case Report and Review of the Literature

et al. 1998

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“…4 AKU is caused by mutation in gene on chromosome 3q2 coding for homogentisate-1, 2-dioxygenase (HGO) enzyme of tyrosine/phenylalanine catabolic pathway. 5 Deficiency of this enzyme results in accumulation and deposition of homogentisic acid and its oxidation product (benzoquinone acetate) in cartilaginous connective tissue. Dark pigmentation of the skin, sclera and nails along with osteoarthritis and cardiac involvement are the main complications of AKU.…”

Section: Introductionmentioning

confidence: 99%

Skin pigmentation, a window to diagnose Alkaptonuria: a very rare entity

et al. 2017

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Alkaptonuria (AKU) or endogenous ochronosis is a very rare inborn error of tyrosine metabolism inherited by autosomal recessive mode. There is complete absence of homogentisic acid oxidase enzyme which results in accumulation of homogentisic acid in cartilaginous connective tissue thus produces ochronotic clinical manifestations. Here we reported a 36 year old woman with bluish pigmentation of pinnae, index fingers (lateral aspect), nails, teeth and sclera. Detailed clinical and investigative workup was done to diagnose patient. Skin biopsy showed changes of ochronosis and urine examination revealed detectable level of homogentisic acid. Classical ocular findings, ochronosis on clinical and HPE and positive urinary tests for homogentisic acid confirmed the diagnosis of alkaptonuria. The highlight of our case is that an asymptomatic patient was detected early by ochronosis prior to development of musculoskeletal or cardiac complications.

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The Human Gene for Alkaptonuria (AKU) Maps to Chromosome 3q

Cited by 92 publications

References 0 publications

Alkaptonuric Ochronosis with Aortic Valve and Joint Replacements and Femoral Fracture: A Case Report and Literature Review

Alkaptonuric Ochronosis with Aortic Valve and Joint Replacements and Femoral Fracture: A Case Report and Literature Review

Alkaptonuria: Case Report and Review of the Literature

Skin pigmentation, a window to diagnose Alkaptonuria: a very rare entity

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