Adenine phosphoribosyltransferase deficiency in children

• Published in: Pediatric nephrology (Berlin, West) West), 2012-04, Vol.27 (4), p.571-579
• Main Authors: Harambat, Jérôme, Bollée, Guillaume, Daudon, Michel, Ceballos-Picot, Irène, Bensman, Albert
• Format: Article
• Language: English
• Subjects: Adenine Phosphoribosyltransferase - deficiency; Adenine Phosphoribosyltransferase - genetics; Adolescent; Allopurinol - therapeutic use; Analysis; Antimetabolites - therapeutic use; Child; Child, Preschool; Chronic kidney failure; Enzymes; Female; Humans; Infant; Kidney diseases; Kidney stones; Laboratories; Male; Medicine; Medicine & Public Health; Metabolism; Metabolism, Inborn Errors - diagnosis; Metabolism, Inborn Errors - drug therapy; Metabolism, Inborn Errors - genetics; Nephrology; Original Article; Pediatrics; Physiological aspects; Purines; Retrospective Studies; Transplants & implants; Urinary tract diseases; Urinary tract infections; Urine; Urogenital system; Urolithiasis - diagnosis; Urolithiasis - drug therapy; Urolithiasis - genetics; Urology; Young Adult
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-011-2037-0

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.