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Two Japanese siblings with arginase-1 deficiency identified using a novel frameshift mutation of ARG1 (p.Lys41Thrfs∗2)

  • Hisakazu Nakajima ORCID logo EMAIL logo and Shota Fukuhara ORCID logo
Published/Copyright: October 18, 2021
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 35 Issue 1

Abstract

We described two Japanese siblings with arginase-1 (ARG1) deficiency. A 10-year-old girl (the proband and elder sister) was referred to our hospital complaining about her short stature. We diagnosed her with ARG1 deficiency, possibly with elevated levels of blood ammonia and plasma arginine. Her younger sister was found to have spastic paraparesis in her lower extremities and short stature at the age of 4 years. The younger sister also had high levels of plasma arginine, instead of normal levels of blood ammonia. Interestingly, they also prefer to avoid protein-rich foods such as meat, soybeans, cow milk, and dairy products. Genetic testing identified compound heterozygous mutations (c.121_122insCTT [p.Lys41Thrfs∗2] and c.298G>A [p.Asp100Asn]) in the ARG1 gene. The ARG1 mutation of p.Lys41Thrfs∗2 is a novel pathogenic mutation according to open databases and literature.

Keywords: arginase-1 deficiency; inherited urea cycle disorder; novel pathogenic mutation
Corresponding author: Hisakazu Nakajima, MD, PhD, Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 6028566, Japan; Department of Pediatrics, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan; and Department of Pediatrics, Midorigaoka Hospital, Takatsuki, Osaka 5611121, Japan, Phone: +(81) 75 251 5571, Fax: +(81) 75 252 1399, E-mail:

Funding source: The Research Grant of Kyoto Prefectural Public University Corporation

Acknowledgments

We gratefully thank our patients for their participation of the genetic analysis. We appreciate Dr. Tomiko Kuhara (Japan Clinical Metabolomics Institute, Ishikawa, Japan) performing metabolome analysis with gas chromatography mass-spectrometry to quantify urinary orotic acid, uracil and other organic acids. We would like to thank Editage (www.editage.com) for English language editing.

  1. Research funding: This study was supported by the Research Grant of Kyoto Prefectural Public University Corporation.

  2. Author contributions: Dr. Hisakazu Nakajima (H.N.) designed the study concept. H.N. obtained informed consent from the proband and her family. H.N. and Dr. Shota Fukuhara (S.F.) contributed to the data collection of th patients and their family. S.F. and H.N. performed the genetic analysis with Sanger sequences. H.N. contribute to the interpretation on the results of the genetic tests, reviewing the databases and the literature. H.N. made initial manuscript. H.N. and S.F. reviewed and amended the manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: The authors have no conflict to declare.

  4. Informed consent: Informed consent was obtained from all individuals and family included in this study.

  5. Ethical approval: This study was approved by the Kyoto Prefectural University of Medicine Medical Studies Ethics Review Board (approval number, ERB-G-80; approval date, June 30, 2019).

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jpem-2021-0436).

Received: 2021-06-27
Accepted: 2021-09-27
Published Online: 2021-10-18
Published in Print: 2022-01-27

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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  18. Case Reports
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  20. Wolfram-like syndrome – another face of a rare disease in children
  21. Two Japanese siblings with arginase-1 deficiency identified using a novel frameshift mutation of ARG1 (p.Lys41Thrfs∗2)
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https://doi.org/10.1515/jpem-2021-0436
Keywords for this article
arginase-1 deficiency; inherited urea cycle disorder; novel pathogenic mutation

Articles in the same Issue

  1. Frontmatter
  2. Review Article
  3. Medullary thyroid carcinoma in children: current state of the art and future perspectives
  4. Original Articles
  5. Newly defined peroxisomal disease with novel ACBD5 mutation
  6. Pediatric adrenocortical tumors cohort characteristics and long-term follow-up at a single Argentinian tertiary center
  7. Sleep disorder and behavior problems in children with type 1 diabetes mellitus
  8. Increased hepcidin levels and non-alcoholic fatty liver disease in obese prepubertal children: a further piece to the complex puzzle of metabolic derangements
  9. Screening for testicular adrenal rest tumors among children with congenital adrenal hyperplasia at King Fahad Medical City, Saudi Arabia
  10. The association between vitamin D levels and metabolic syndrome components among metropolitan adolescent population
  11. Utility of wrist circumference in recognition of metabolic syndrome in overweight and obese South Indian children and adolescents
  12. Ketoacidosis in new-onset type 1 diabetes: did the severity increase during the COVID-19 pandemic?
  13. Predictors of decreased bone mineral density in childhood systemic lupus erythematosus: possible role of osteoprotegerin gene polymorphisms
  14. Psychiatric behavioral effect and characteristics of type 2 diabetes mellitus on Japanese patients with Prader-Willi syndrome: a preliminary retrospective study
  15. Biochemical predictors of metabolically unhealthy obesity in children and adolescents
  16. Adiposity rebound in very-low-birth-weight infants
  17. The association between a metabolically healthy overweight/obesity phenotype and markers of inflammation among Chinese children and adolescents aged 10–18 years
  18. Case Reports
  19. Management of perinatal HPP during critical illness/ECMO
  20. Wolfram-like syndrome – another face of a rare disease in children
  21. Two Japanese siblings with arginase-1 deficiency identified using a novel frameshift mutation of ARG1 (p.Lys41Thrfs∗2)
  22. An atypical presentation of a pathogenic STK11 gene variant in siblings not fulfilling the clinical diagnostic criteria for Peutz-Jeghers Syndrome
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