primary hyperoxaluria type 1

Primary hyperoxaluria type 1 is a rare metabolic disorder that affects glyoxylate metabolism in the liver, leading to an excessive accumulation of oxalate. The condition is caused by mutations in the AGXT gene, which encodes the enzyme L-alanine:glyoxylate aminotransferase, essential for normal oxalate processing. It typically presents in childhood with symptoms related to kidney involvement, although the exact prevalence is not well established. Overall, the clinical presentation can range from mild kidney stone formation to more severe kidney damage and systemic complications.

The clinical features of primary hyperoxaluria type 1 primarily involve the kidneys. Individuals nearly always experience nephrocalcinosis, hyperoxaluria, renal insufficiency, and dehydration, with laboratory evaluations commonly showing elevated levels of urinary glyoxylic acid and glycolic acid. These features often prompt further investigation when recurrent kidney stones or unexplained renal dysfunction occur. Not all individuals experience every detail in the same way, and the severity of symptoms can vary considerably.

Primary hyperoxaluria type 1 is caused by mutations in the AGXT gene, which plays a crucial role in the metabolism of glyoxylate by coding for the enzyme L-alanine:glyoxylate aminotransferase. Disruption of this enzyme leads to the accumulation of oxalate in the body. The condition is inherited in an autosomal recessive pattern, meaning that an affected individual has inherited two copies of the mutated gene—one from each parent—and there is a 25% chance for each sibling of affected parents to inherit the condition. Genetic counseling can help families understand these inheritance patterns and plan for the future.

Currently, management of primary hyperoxaluria type 1 focuses on supportive care and symptom management rather than any specifically approved treatment. Treatment plans are tailored to the individual and typically include strategies to manage kidney complications and maintain proper hydration, often involving a multidisciplinary team. In addition, there are several investigational therapies under orphan drug designation that are being studied, but they are not yet approved. Patients should discuss treatment options with their healthcare team and consider genetic counseling as part of their ongoing care.

The outlook for individuals with primary hyperoxaluria type 1 varies widely, with disease progression dependent on the severity of oxalate accumulation and kidney involvement. With current standards of care, many individuals benefit from advances in supportive management, which can help improve quality of life and delay the progression to end-stage renal disease. Outcomes described in medical literature continue to evolve as standards of care improve, and regular monitoring is essential to address emerging complications. Families often find it helpful to connect with genetic counselors and specialists experienced in managing this condition.

There is an active research effort in primary hyperoxaluria type 1, with several clinical trials currently investigating new treatment approaches. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility for emerging therapies.