hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome

Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome is a multisystem condition that affects metabolic balance, kidney function, and the respiratory system. It is caused by pathogenic variants in the SARS2 gene. Affected individuals present in infancy with features including feeding difficulties, failure to thrive, and global developmental delay, reflecting central nervous system involvement. The condition is very rare, affecting fewer than 1 in a million people, and follows an autosomal recessive pattern.

Individuals with hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome commonly present with a combination of metabolic and renal abnormalities such as hypochloremic metabolic alkalosis, renal salt wasting, increased blood urea nitrogen, and hyperuricemia. In addition, hyperechogenic kidneys and diabetes mellitus are consistently observed, while premature birth, feeding difficulties, failure to thrive, and increased circulating lactate concentration are early signs that often prompt further evaluation. Pulmonary arterial hypertension is also a prominent and concerning feature. Global developmental delay, indicative of central nervous system involvement, is universally present, and other variable features such as pancytopenia, respiratory failure or insufficiency, proteinuria, type 2 muscle fiber atrophy, and hypotonia may occur in a subset of affected individuals. Not all individuals experience every feature, and severity varies considerably.

This syndrome is caused by pathogenic variants in the SARS2 gene, which is essential for normal cellular function. The condition is inherited in an autosomal recessive manner, meaning that an affected individual receives one mutated copy of the gene from each parent. It is more common when parents share a common ancestor because both are more likely to carry the same rare variant. Genetic counseling is recommended for families to better understand recurrence risks and explore family planning options.

Currently, management focuses on supportive care and symptom control, with treatment tailored to each individual. A multidisciplinary approach is critical to address the various aspects of the condition, including careful monitoring of metabolic, renal, and respiratory functions. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Genetic counseling is also recommended so that families can better understand the condition and available management options. Patients should discuss treatment options with their healthcare team to determine the most appropriate interventions for their specific situation.

Outcomes vary widely depending on symptom severity, age at diagnosis, and access to specialized care. Many individuals face persistent challenges including metabolic imbalances, renal dysfunction, and respiratory complications, while the presence of global developmental delay often necessitates ongoing supportive therapies. With current standards of care, interventions are continually improving, and outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists, such as genetic counselors and metabolic experts, to gain guidance and support throughout their journey.