primary hyperoxaluria type 2

Primary hyperoxaluria type 2 is a rare metabolic disorder affecting glyoxylate metabolism and primarily involves the kidneys. It is caused by pathogenic variants in the GRHPR gene leading to a deficiency of the glyoxylate reductase/hydropyruvate reductase enzyme. Most individuals present in childhood with symptoms related to kidney stone formation and calcifications. The condition is very rare, affecting fewer than 1 in 1,000,000 people.

The clinical presentation of primary hyperoxaluria type 2 includes consistently elevated urinary L-glycerate levels and hyperoxaluria, which are always observed. Many affected individuals experience calcium oxalate kidney stones, and some may develop renal insufficiency over time. Not all individuals experience all features, and severity varies considerably. Early kidney-related symptoms often lead to the diagnosis, while complications such as nephrocalcinosis and progressive renal impairment can develop later.

This condition is caused by pathogenic variants in the GRHPR gene, which leads to a deficiency in the enzyme glyoxylate reductase/hydropyruvate reductase. It is inherited in an autosomal recessive pattern, meaning that an individual must inherit two altered copies of the GRHPR gene, one from each parent, to be affected. This condition is more common when parents share a common ancestor, as this increases the likelihood that both carry the same rare genetic variant. As with other autosomal recessive disorders, each child of two carrier parents has a 25% chance of being affected.

Currently, management focuses on supportive care and symptom management, as there are no approved treatments specifically for primary hyperoxaluria type 2. Treatment is tailored to the individual’s needs and typically involves a multidisciplinary team to address complications, including kidney stone management and strategies to preserve renal function. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended to help families understand the condition and associated recurrence risks.

Outcomes for primary hyperoxaluria type 2 vary depending on symptom severity, age at diagnosis, and access to specialized care. With current standards of care, many individuals manage their condition into adulthood, although some may experience progressive renal complications. Severity and symptoms vary widely between individuals, and the overall course may include periods of stability interspersed with challenges related to kidney function. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with genetic counselors for guidance on long-term management.

Several clinical trials are currently investigating new treatment approaches for primary hyperoxaluria type 2. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.