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Alkaptonuria in France: past experience and lessons for the future

  • Alkaptonuria
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Alkaptonuria (AKU) is an autosomal recessive disorder due to homogentisate 1,2-dioxygenase (HGD) deficiency in the liver and characterized by a triad of signs, according to chronology of appearance: homogentisic aciduria (HGA ) or alkaptonuria, ochronosis then ochronotic arthropathy. This inborn error of metabolism is caused by mutations in the HGD gene. In this work we report observations of 96 AKU French patients from 81 families collected in the literature since 1882 and from our personal contribution since 1986, giving an incidence of the disease of around 1:680,000 (96/64.106). As expected for an autosomal recessive disorder the main findings of this study were: a slight predominance of males (51/93, 54,8%) over females (42/93, 45,2%), a strong predominance of sibships with one affected individual (68/81, 84,0%) over sibships with two (11/81, 13.6%) and three(2/81, 2.4%) affected individuals. AKU families are scaterred among the French territory suggesting that most cases occured in non-consanguineous unions. Consanguinity was only found in five families. Other peculiarities of this study were (a) ten of these families have both parents from a foreign geographical origin: Poland(3), Italy(3), Portugal(2), Ukraine(1) and India(1) and four families with only one foreign parent (Algeria, Armenia, Serbia, UK), (b) HGD mutations were found in 23 families, (c) four of theses 96 patients were seen by us respectively 28, 29, 39 and 45 years after their report in the literature and (d) seven patients present cardiac and/or renal complications.

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Acknowledgement

We are grateful to all members of the AKU families for their cooperation and donating of blood samples, to Serge Sireau, president of ALCAP for fruitful collaboration, to MD colleagues who have kindly send us their patients particularly Pr.J.Serratrice from Marseille and Dr.Blankaert from Arras. We wish to thank Penalva team of Madrid for identification of mutations on the HGD gene from 1988 to 2001 and A.Zatkova of Bratislava since 2008. The author thanks Olivier Timmis for help preparing the manuscript.

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  1. Laboratoire de biochimie et biologie moléculaire, Aix-Marseille Université, Campus Santé Timone, 27 Boulevard Jean Moulin, 13385, Marseille, cedex5, France

    Robert Raphael Aquaron

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Correspondence to Robert Raphael Aquaron.

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Communicated by: Lakshminarayan Rao Ranganath

Competing interest: None declared.

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Aquaron, R.R. Alkaptonuria in France: past experience and lessons for the future. J Inherit Metab Dis 34, 1115–1126 (2011). https://doi.org/10.1007/s10545-011-9392-7

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