cystathioninuria

Cystathioninuria is a metabolic disorder caused by a deficiency of the enzyme cystathionine gamma-lyase, which is encoded by the CTH gene. It is generally considered a benign condition and is typically pyridoxine-dependent, although rare non-dependent forms exist. While many individuals experience a mild course, some cases have been associated with intellectual impairment and other neurological symptoms. This condition is inherited in an autosomal recessive pattern and is uncommon, affecting roughly 1 to 9 per 100,000 individuals.

The hallmark feature of cystathioninuria is the biochemical finding of elevated cystathionine levels, which is present in all affected individuals. In addition, a subset of patients may experience intellectual disability, seizures, and related cognitive challenges, highlighting the condition’s impact on neurological development. Other reported features include cystathioninemia, and less commonly, nephrolithiasis, tremor, talipes equinovarus, and abnormal pinna morphology. Not all individuals experience every feature, and severity varies considerably.

Cystathioninuria is caused by pathogenic variants in the CTH gene, which encodes the enzyme cystathionine gamma-lyase. This enzyme plays a critical role in the metabolism of methionine, and its deficiency leads to the accumulation of cystathionine. The condition is inherited in an autosomal recessive manner, meaning that an affected individual inherits a pathogenic variant from each parent. As a result, each sibling of an affected individual has a 25% chance of being affected, making genetic counseling an important step for families.

Currently, management for cystathioninuria focuses on supportive care and symptom management, with many patients benefiting from pyridoxine supplementation. Although there are no FDA-approved treatments specifically for this condition, treatment is tailored to the individual’s clinical needs and typically involves a multidisciplinary team. Genetic counseling is also recommended to help families understand the inheritance pattern and to discuss family planning, while ongoing monitoring helps address any evolving symptoms.

Cystathioninuria is generally regarded as a benign condition; however, there is notable variability in outcomes. While many individuals maintain a stable course, some may experience cognitive and neurological challenges such as intellectual disability or seizures. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with metabolic specialists and genetic counselors to discuss individual prognosis and long-term care options.