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Background <p>Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder caused by pathogenic variants in the <i>AGXT</i> gene. In regions with a high prevalence of consanguinity, the burden of PH1 is expected to be increased; however, data on its epidemiology in Tunisia remain scarce. This study aimed to estimate the minimum observed clinical prevalence of PH1 in Tunisia, to assess the expected genetic burden based on published pathogenic allele frequency data, and to describe the clinical and molecular spectrum of the disease in this cohort.</p> Methods <p>We retrospectively analyzed genetically confirmed PH1 patients referred to a major national tertiary referral center in Tunisia between 2011 and 2025, in whom molecular diagnosis was established by systematic Sanger sequencing of the <i>AGXT</i> gene. The minimum observed clinical prevalence was estimated using national population data. The expected genetic burden was derived using Hardy–Weinberg equilibrium based on published gene-based pathogenic <i>AGXT</i> allele frequency estimates from large population databases (gnomAD). A sensitivity analysis incorporating population-level consanguinity was performed.</p> Results <p>A total of 104 PH1 patients from 55 unrelated families were identified. Most patients presented during childhood (at least 77%), mainly with nephrolithiasis or nephrocalcinosis, while kidney failure (CKD stage 5) was already present in at least half of the probands. The minimum observed clinical prevalence of PH1 in Tunisia was estimated at 8.7 cases per million inhabitants. By contrast, gene-based estimates suggested that approximately 200–300 individuals would be expected to be affected in an outbred population of 12 million. A marked founder effect was observed for the c.731&#xa0;T&gt;C (p.Ile244Thr) variant.</p> Conclusions <p>PH1 represents a significant cause of pediatric kidney disease in Tunisia and is likely underdiagnosed. These findings support the need for increased clinical awareness, early genetic testing, and timely diagnosis to optimize patient management in the era of disease-modifying therapies.</p> Graphical abstract <p></p>

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Clinical and molecular spectrum of primary hyperoxaluria type 1 in Tunisia: pediatric presentation and minimum observed prevalence

  • 期刊论文

  • 发表日期：

    2026年4月20日

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  • Ridha M’rad,
  • Mahdi Kammoun,
  • Ahlem Achour,
  • Emna Koubaa,
  • Abir Bousetta,
  • Hayet Kaaroud,
  • Mohamed Karim Zouaghi,
  • Ezzeddine Abderrahim,
  • Tahar Gargah,
  • Mediha Trabelsi

摘要

Background

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder caused by pathogenic variants in the AGXT gene. In regions with a high prevalence of consanguinity, the burden of PH1 is expected to be increased; however, data on its epidemiology in Tunisia remain scarce. This study aimed to estimate the minimum observed clinical prevalence of PH1 in Tunisia, to assess the expected genetic burden based on published pathogenic allele frequency data, and to describe the clinical and molecular spectrum of the disease in this cohort.

Methods

We retrospectively analyzed genetically confirmed PH1 patients referred to a major national tertiary referral center in Tunisia between 2011 and 2025, in whom molecular diagnosis was established by systematic Sanger sequencing of the AGXT gene. The minimum observed clinical prevalence was estimated using national population data. The expected genetic burden was derived using Hardy–Weinberg equilibrium based on published gene-based pathogenic AGXT allele frequency estimates from large population databases (gnomAD). A sensitivity analysis incorporating population-level consanguinity was performed.

Results

A total of 104 PH1 patients from 55 unrelated families were identified. Most patients presented during childhood (at least 77%), mainly with nephrolithiasis or nephrocalcinosis, while kidney failure (CKD stage 5) was already present in at least half of the probands. The minimum observed clinical prevalence of PH1 in Tunisia was estimated at 8.7 cases per million inhabitants. By contrast, gene-based estimates suggested that approximately 200–300 individuals would be expected to be affected in an outbred population of 12 million. A marked founder effect was observed for the c.731 T>C (p.Ile244Thr) variant.

Conclusions

PH1 represents a significant cause of pediatric kidney disease in Tunisia and is likely underdiagnosed. These findings support the need for increased clinical awareness, early genetic testing, and timely diagnosis to optimize patient management in the era of disease-modifying therapies.

Graphical abstract