Genotypic and clinical characteristics of long-term surviving adult patients with urea cycle disorders in Japan
- 1Department of Pediatrics, Faculty of Life Sciences, Kumamoto University, 1–1–1 Honjo, Chuo-ku, Kumamoto, 860–8556 Japan
- 2Department of Pediatrics, Kumamoto University Hospital, Kumamoto, Japan
Abstract
Background: Urea cycle disorders (UCDs) are rare inherited metabolic conditions characterized by impaired nitrogen disposal due to defects in enzymes or transporters. Although genotype–phenotype correlations have been investigated in patients with UCDs, the genetic characteristics and long-term clinical outcomes of adult survivors remain poorly understood. This study aimed to investigate the genotypic and clinical characteristics of adult long-term survivors with UCDs in Japan and to evaluate genotype–phenotype correlations.
Methods: We conducted a nationwide survey and collected clinical and genetic data from 116 adult patients with UCDs. Pathogenic variants were identified in 48 patients, and clinical data including age at onset, peak plasma ammonia levels, intellectual outcomes, and long-term prognosis were analyzed. Particular attention was paid to genotype–phenotype correlations in male patients with ornithine transcarbamylase deficiency (OTCD).
Results: Among 48 patients with identified variants (34 OTCD, 2 CPS1D, 6 ASS1D, 3 ASLD, 1 ARG1D, and 2 HHH syndrome), most OTCD variants in males were associated with late-onset phenotypes. Intellectual disability was present in 43.2% (19/44) of patients and was significantly associated with peak ammonia levels exceeding 360 μmol/L (p = 0.046), particularly in male OTCD patients (p = 0.018). Clinical presentations varied even among patients with identical variants.
Conclusion: This is the first study to characterize the genetic and clinical profiles of adult long-term survivors with UCDs in Japan. These findings suggest that genotype information may help predict disease onset and clinical severity, although genotype alone is insufficient to fully predict long-term clinical outcomes.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13023-026-04524-x.
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BibTeX
@article{kido2026genotypic,
title = {{Genotypic and clinical characteristics of long-term surviving adult patients with urea cycle disorders in Japan}},
author = {Jun Kido and Keishin Sugawara and Naomi Yano and Kimitoshi Nakamura},
journal = {Orphanet Journal of Rare Diseases},
year = {2026},
month = jul,
doi = {10.1186/s13023-026-04524-x},
url = {https://doi.org/10.1186/s13023-026-04524-x},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Genotypic and clinical characteristics of long-term surviving adult patients with urea cycle disorders in Japan
AU - Jun Kido
AU - Keishin Sugawara
AU - Naomi Yano
AU - Kimitoshi Nakamura
PY - 2026
DA - 2026/07/01
JO - Orphanet Journal of Rare Diseases
DO - 10.1186/s13023-026-04524-x
UR - https://doi.org/10.1186/s13023-026-04524-x
AB - Background: Urea cycle disorders (UCDs) are rare inherited metabolic conditions characterized by impaired nitrogen disposal due to defects in enzymes or transporters. Although genotype–phenotype correlations have been investigated in patients with UCDs, the genetic characteristics and long-term clinical outcomes of adult survivors remain poorly understood. This study aimed to investigate the genotypic and clinical characteristics of adult long-term survivors with UCDs in Japan and to evaluate genotype–phenotype correlations. Methods: We conducted a nationwide survey and collected clinical and genetic data from 116 adult patients with UCDs. Pathogenic variants were identified in 48 patients, and clinical data including age at onset, peak plasma ammonia levels, intellectual outcomes, and long-term prognosis were analyzed. Particular attention was paid to genotype–phenotype correlations in male patients with ornithine transcarbamylase deficiency (OTCD). Results: Among 48 patients with identified variants (34 OTCD, 2 CPS1D, 6 ASS1D, 3 ASLD, 1 ARG1D, and 2 HHH syndrome), most OTCD variants in males were associated with late-onset phenotypes. Intellectual disability was present in 43.2% (19/44) of patients and was significantly associated with peak ammonia levels exceeding 360 μmol/L (p = 0.046), particularly in male OTCD patients (p = 0.018). Clinical presentations varied even among patients with identical variants. Conclusion: This is the first study to characterize the genetic and clinical profiles of adult long-term survivors with UCDs in Japan. These findings suggest that genotype information may help predict disease onset and clinical severity, although genotype alone is insufficient to fully predict long-term clinical outcomes. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13023-026-04524-x.
SN - 1750-1172
ER -