Abstract
Unlike complete deficiency of hypoxanthine phosphoribosyltransferase (HPRT) (i.e., Lesch–Nyhan syndrome), partial HPRT deficiency causes HPRT-related hyperuricemia without neurological symptoms. Herein, we describe a 22-year-old man without neurological symptoms that presented gout, hyperuricemia (serum urate level, 12.2 mg/dL), multiple renal microcalculi, and a family history of juvenile gout that was exhibited by his brother and grandfather. Genetic testing revealed a novel missense mutation, c.103G>A (p.V35M), in the HPRT1 gene, and biochemical testing (conducted using the patient’s erythrocytes) showed that the patient retained only 12.4% HPRT enzymatic activity compared to that exhibited by a healthy control subject. We thus diagnosed the patient with HPRT-related hyperuricemia caused by partial HPRT deficiency. After his serum urate level was controlled via treatment with febuxostat, his gout did not recur. Thus, this study emphasizes that HPRT deficiency should be considered as a potential cause of familial juvenile gout, even in the absence of neurological symptoms.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Torres RJ, Puig JG. Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome. Orphanet J Rare Dis. 2007;2:48.
Jinnah HA, Ceballos-Picot I, Torres RJ, Visser JE, Schretlen DJ, Verdu A, et al. Attenuated variants of Lesch-Nyhan disease. Brain. 2010;133:671–89.
Mori T, Hosomichi K, Chiga M, Mandai S, Nakaoka H, Sohara E, et al. Comprehensive genetic testing approach for major inherited kidney diseases, using next-generation sequencing with a custom panel. Clin Exp Nephrol. 2017;21:63–75.
Yang J, Yan R, Roy A, Xu D, Poisson J, Zhang Y. The I-TASSER suite: protein structure and function prediction. Nat Methods. 2015;12:7–8.
Gordon RB, Thompson L, Emmerson BT. Erythrocyte phosphoribosylpyrophosphate concentrations in heterozygotes for hypoxanthine-guanine phosphoribosyltransferase deficiency. Metabolism. 1974;23:921–7.
Fu R, Ceballos-Picot I, Torres RJ, Larovere LE, Yamada Y, Nguyen KV, et al. Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder. Brain. 2014;137:1282–303.
Madeo A, Di Rocco M, Brassier A, Bahi-Buisson N, De Lonlay P, Ceballos-Picot I. Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency. Mol Genet Metab. 2019;127:147–57.
Lesch-Nyhan Disease International Study Group. https://www.lesch-nyhan.org/ Accessed Dec 2019.
Stenson PD, Mort M, Ball EV, Shaw K, Phillips A, Cooper DN. The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Hum Genet. 2014;133:1–9.
ClinVar: https://www.ncbi.nlm.nih.gov/clinvar/ Accessed Dec 2019.
Genomes Project C, Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, et al. A map of human genome variation from population-scale sequencing. Nature. 2010;467:1061–73.
The Genome Aggregation Database (gnomAD) https://www.biorxiv.org/content/10.1101/531210v3 Accessed Dec 2019.
Yamaguchi-Kabata Y, Nariai N, Kawai Y, Sato Y, Kojima K, Tateno M, et al. iJGVD: an integrative Japanese genome variation database based on whole-genome sequencing. Hum Genome Var. 2015;2:15050.
Torres RJ, Puig JG, Jinnah HA. Update on the phenotypic spectrum of Lesch-Nyhan disease and its attenuated variants. Curr Rheumatol Rep. 2012;14:189–94.
Takeuchi Y, Mishima E, Shima H, Akiyama Y, Suzuki C, Suzuki T, et al. Exonic mutations in the SLC12A3 gene cause exon skipping and premature termination in Gitelman syndrome. J Am Soc Nephrol. 2015;26:271–9.
Mishima E, Mori T, Sohara E, Uchida S, Abe T, Ito S. Inherited, not acquired, Gitelman syndrome in a patient with Sjogren's syndrome: importance of genetic testing to distinguish the two forms. CEN Case Rep. 2017;6:180–4.
Mishima E, Fukuda S, Shima H, Hirayama A, Akiyama Y, Takeuchi Y, et al. Alteration of the intestinal environment by lubiprostone is associated with amelioration of adenine-induced CKD. J Am Soc Nephrol. 2015;26:1787–94.
Acknowledgements
This work is partially supported by Tohoku University Center for Gender Equality Promotion (TUMUG) Support Project.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
All of the authors have declared no competing interests.
Human and animal rights statement
This article does not describe any studies with human participants performed by any of the authors.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Mishima, E., Mori, T., Nakajima, Y. et al. HPRT-related hyperuricemia with a novel p.V35M mutation in HPRT1 presenting familial juvenile gout. CEN Case Rep 9, 210–214 (2020). https://doi.org/10.1007/s13730-020-00459-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13730-020-00459-9