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Adenine phosphoribosyltransferase deficiency in children

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Abstract

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder characterized by 2,8-dihydroxyadenine (2,8-DHA) crystalluria that can cause nephrolithiasis and chronic kidney disease. The aim of our study was to assess the clinical presentation, diagnosis, and outcome of APRT deficiency in a large pediatric cohort. All pediatric cases of APRT deficiency confirmed at the same French reference laboratories between 1978 and 2010 were retrospectively reviewed. Twenty-one patients from 18 families were identified. The median age at diagnosis was 3 years. Diagnosis was made after one or more episodes of nephrolithiasis (17 patients), after urinary tract infection (1 patient), and by family screening (3 patients). The diagnosis was based on stone analysis and microscopic examination of urine and/or enzymatic determination of APRT on red blood cells. All children had null APRT enzyme activity in erythrocytes. APRT gene sequencing was performed on 18 patients, revealing six homozygous and 12 compound heterozygous mutations. At diagnosis, half of the patients had decreased kidney function, and two children presented with acute renal failure. Allopurinol treatment was given to all patients at a median dose of 9 mg/kg/day. After a median follow-up of 5 years, all patients showed stabilization or improvement of kidney function, normal growth and development, and six patients had recurrence of nephrolithiasis. Based on these results, we conclude that an excellent outcome can be achieved in children with APRT deficiency who receive the proper treatment.

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Abbreviations

2,8-DHA:

2,8-dihydroxyadenine

APRT:

Adenine phosphoribosyltransferase

ESRD:

End-stage renal disease

eGFR:

Estimated glomerular filtration rate

IQR:

Interquartile range

SDS:

Standard Deviation Score

UTI:

Urinary tract infection

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Acknowledgments

We sincerely thank Dr. Patrizia Bonneau-Amati (Angers, France), Dr. Ana Medeira, (Lisbon, Portugal) for additional data collection, and Véronique Droin, Lionel Mockel, Cécile Dollinger, Lucile Boutaud, and Delphine Guillemot from the Laboratoire de Biochimie Métabolique, Hôpital Necker-Enfants Malades, Paris, for their technical assistance.

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Authors and Affiliations

  1. Service de Pédiatrie, Centre Hospitalier Universitaire de Bordeaux, Centre de référence Maladies Rénales Rares du Sud Ouest, Bordeaux, France

    Jérôme Harambat

  2. Service de Néphrologie, Hôpital Necker-Enfants Malades, Assistance Publique–Hôpitaux de Paris (APHP), Université Descartes, Sorbonne Paris Cité, Paris, France

    Guillaume Bollée

  3. Laboratoire de Biochimie A, Hôpital Necker-Enfants Malades, APHP, Université Descartes, Sorbonne Paris Cité, Paris, France

    Michel Daudon

  4. Laboratoire de Biochimie Métabolique, Hôpital Necker-Enfants Malades, APHP, Université Descartes, Sorbonne Paris Cité, Paris, France

    Irène Ceballos-Picot

  5. Service de Néphrologie Pédiatrique, Hôpital Armand Trousseau, APHP, Université Pierre et Marie Curie, Paris, France

    Albert Bensman

  6. Hôpital Pellegrin-Enfants, place Amélie Raba Léon, 33076, Bordeaux Cedex, France

    Jérôme Harambat

Authors
  1. Jérôme Harambat
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  2. Guillaume Bollée
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  3. Michel Daudon
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  4. Irène Ceballos-Picot
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  5. Albert Bensman
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Consortia

APRT Study Group

Corresponding author

Correspondence to Jérôme Harambat.

Additional information

Jérôme Harambat and Guillaume Bollée contributed equally to this study.

Irène Ceballos-Picot and Albert Bensman contributed equally to this study.

The members and affiliations of the APRT Study Group are: Thierry Boussemart (Centre Hospitalier du Mans, Service de Pédiatrie, Le Mans, France); Gérard Champion (Centre Hospitalier Universitaire d’Angers, Service de Pédiatrie, Angers, France); Sophie Taque (Centre Hospitalier Universitaire de Rennes, Service de Pédiatrie, Rennes, France); Margarida Almeida (Hospital Universitário de Santa María, Serviço de Pediatria, Lisbon, Portugal); Didier Bernon (Centre Hospitalier de La Rochelle, Service de Néphrologie, La Rochelle, France); Céline Dheu (Centre Hospitalier Universitaire de Strasbourg, Service de Pédiatrie, Strasbourg, France); Susana Ferrando Monleón (Hospital de la Ribera, Servicio de Pediatría, Alzira, Valencia, Spain); Benjamin Horen (Centre Hospitalier de Bigorre, Service de Pédiatrie, Tarbes, France); Arnaud Garnier (Centre Hospitalier Universitaire de Toulouse, Service de Néphrologie Pédiatrique, Toulouse, France); Geneviève Guest (APHP, Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, Paris, France); Astrid Godron (Centre Hospitalier Universitaire de Bordeaux, Service de Pédiatrie, Bordeaux, France); Bertrand Knebelmann (APHP, Service de Néphrologie, Hôpital Necker-Enfants Malades, Paris, France); Brigitte Llanas (Centre Hospitalier Universitaire de Bordeaux, Service de Pédiatrie, Bordeaux, France); Giuseppina Marra (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Servizio di Nefrologia Pediatrica, Milan, Italy); Michel Rincé (Centre Hospitalier Universitaire de Limoges, Service de Néphrologie, Limoges, France); Jean-François Subra (Centre Hospitalier Universitaire d’Angers, Service de Néphrologie, Angers, France); François Vrtovsnik (APHP, Service de Néphrologie, Hôpital Bichat, Paris, France)

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Harambat, J., Bollée, G., Daudon, M. et al. Adenine phosphoribosyltransferase deficiency in children. Pediatr Nephrol 27, 571–579 (2012). https://doi.org/10.1007/s00467-011-2037-0

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  • DOI: https://doi.org/10.1007/s00467-011-2037-0

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