Case series and literature review of primary hyperoxaluria type 1 in Chinese patients

Abstract

Based on the single-center case reports and all reported patients with primary hyperoxaluria type 1 (PH1) in China, this study discussed the clinical and genetic characteristics of this disease retrospectively. We reported and validated a novel genetic variation c.302 T > G: the clinical phenotypes of the two siblings were similar, in which both had onset in infancy, mainly manifested as renal insufficiency, and died within 6 months out of end-stage renal disease. The literature review is the first to summarize the Chinese patients with PH1 up to now. Forty-eight Chinese patients were included, containing 7 adults and 41 children. The median onset age was 51 months, and the ratio of male to female was 2.69:1. It showed a poor prognosis: 51.1% of Chinese primary hyperoxaluria type 1 patients suffered from end-stage renal disease, and 38.9% of patients died. Urolithiasis was the most common clinical manifestation both in adults and children, while infant-onset patients generally presented with renal insufficiency and had a higher mortality of 75.0%. One hundred and forty-nine AGXT mutant alleles are currently known in the Chinese population, c.33dupC and c.815_816insGA were the most common AGXT genes, accounting for 12.0% and 10.1% of allele frequencies, respectively. The exons 1, 2, 6, and 8 were the most common locations of gene variants, accounting for 78% of all variants, which will be promising targets of DNA sequencing for primary hyperoxaluria type 1.

Navigating the Evolving Landscape of Primary Hyperoxaluria: Traditional Management Defied by the Rise of Novel Molecular Drugs

“…PH1, the most severe form of PH, typically presents initial symptoms PH1 accounts for approximately 80% of all PH cases (Table 1) [23]. The pathogenic gene AGXT, situated on 2q37.3 (MIM# 259900), has been associated with 220 diseasecausing mutations (http://www.hgmd.cf.ac.uk, accessed on date 5 April 2024), disrupting AGT function via the loss of catalytic activity, mislocalization, accelerated degradation or protein aggregation [24,25]. The prevalent mutation in PH1 is p.G170R, associated with AGT mislocalization, which accounts for about 28-30% of mutated alleles, primarily found in Western populations [10,26,27].…”