Inherited metabolic disorders are genetic conditions that result in metabolism problems. Most people with inherited metabolic disorders have a defective gene that results in an enzyme deficiency. There are hundreds of different genetic metabolic disorders, and their symptoms, treatments, and prognoses vary widely.

Urea cycle disorders (UCD)

Urea cycle disorders are a group of metabolic diseases that affect a specific enzyme or transporter in the urea cycle leading to elevated ammonia or glutamine levels in the circulation. Symptoms of the disorder can begin at any age, with more severe defects beginning early in life. UCD patients may experience episodes, called hyperammonemic crises, when ammonia levels in the blood become excessively high, which can result in irreversible brain damage, coma, or death. Beyond hyperammonemic crises there are also more subtle symptoms including vomiting, refusal to feed, irritability, muscular hypotonia as well as delayed motor and psychointellectual development. As a group, these disorders occur in 1 in 35,000 newborns.

Arginase 1 deficiency

Arginase 1 deficiency (ARG1-D) is one of the UCD subtypes. It shares overlapping features and the most prominent is the impairment in excreting nitrogen. However, in ARG1-D, the hyperammonaemia is generally less severe and instead these patients show spasticity, which other subtypes do not. The principal defect in ARG1-D leads to accumulation of plasma arginine, which occurs in almost all patients with this disorder. Patients are often diagnosed in late infancy or early childhood and the symptoms include spasticity, seizures, developmental delay, intellectual disability, and early mortality.