Primary hyperoxaluria type 1 in children: clinical and laboratory manifestations and outcome

Primary hyperoxaluria (PH) results from genetic mutations in different genes of glyoxylate metabolism, which cause significant increases in production of oxalate by the liver. This study aimed to report clinical and laboratory manifestations and outcome of PH type 1 in children in our center.

A single-center observational cohort study was conducted at Children's University Hospital in Damascus, and included all patients admitted from 2018 to 2020, with a diagnosis of hyperoxaluria (urinary oxalate excretion > 45 mg/1.73 m²/day, or > 0.5 mmol/1.73 m²/day). PH type 1 (PH1) diagnosis was established by identification of biallelic pathogenic variants (compound heterozygous or homozygous mutations) in AGXT gene on molecular genetic testing.

The study included 100 patients with hyperoxaluria, with slight male dominance (57%), and median age 1.75 years (range, 1 month-14 years). Initial complaint was urolithiasis or nephrocalcinosis in 47%, kidney failure manifestations in 29%, and recurrent urinary tract infection in 24%. AGXT mutations were detected in 40 patients, and 72.5% of PH1 patients had kidney failure at presentation. Neither gender, age nor urinary oxalate excretion in 24 h had statistical significance in distinguishing PH1 from other forms of hyperoxaluria (P-Value > 0.05). Parental consanguinity, family history of kidney stones, bilateral nephrocalcinosis, presence of oxalate crystals in random urine sample, kidney failure and mortality were statistically significantly higher in PH1 (P-values < 0.05). Mortality was 32.5% among PH1 patients, with 4 PH1 patients (10%) on hemodialysis awaiting combined liver-kidney transplantation.

PH1 is still a grave disease with wide variety of clinical presentations which frequent results in delays in diagnosis, thus kidney failure is still a common presentation. In Syria, we face many challenges in diagnosis of PH, especially PH2 and PH3, and in management, with hopes that diagnosis tools and modern therapies will become available in our country. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.