GTP cyclohydrolase I deficiency

GTP cyclohydrolase I deficiency is a condition where the enzyme GTP cyclohydrolase I is lower than normal. This enzyme is important for making a helper molecule called BH4, which helps other enzymes work correctly. When there is less BH4, the activity of enzymes that help in making important brain chemicals is reduced. This can affect movement and other neurological functions. There is a range of severity in this condition. Some people, especially those with only one altered copy of the gene (autosomal dominant form), may have few symptoms or mild movement issues such as dopa-responsive dystonia. Others, especially those with two affected copies (autosomal recessive form), tend to have more severe neurological symptoms and may be identified early through newborn screening due to high levels of phenylalanine. Overall, this condition shows a spectrum of signs based on the enzyme activity remaining in the body.

People with GTP cyclohydrolase I deficiency can have a wide range of symptoms. Many individuals with one altered gene may have mild or no symptoms, or they might experience movement problems such as dopa-responsive dystonia. In some cases, symptoms may also include signs similar to Parkinson’s disease, focal dystonia, or issues that resemble cerebral palsy or spastic paraplegia. Those with the more severe, recessive form may show higher levels of phenylalanine along with serious neurological problems.

This condition is caused by changes in the gene responsible for producing the enzyme GTP cyclohydrolase I. The genetic changes can be inherited in different ways, with some forms being autosomal dominant and others autosomal recessive. The severity of the condition is linked to how much enzyme activity remains, which explains why some people have only mild symptoms while others have more severe features.

Treatment options for people with this condition vary depending on the severity of the symptoms. Many individuals, particularly those with dopa-responsive dystonia, respond well to treatment with levodopa, which can help improve movement issues. In more severe cases, other medications such as BH4 and 5-hydroxytryptophan may be used along with levodopa. Although treatment can improve symptoms, it may not always stop the progression of severe neurological problems.

The outlook for people with GTP cyclohydrolase I deficiency varies. People with milder, autosomal dominant forms often have a good response to levodopa treatment and can experience significant improvement, especially regarding movement issues. However, those with the severe autosomal recessive form may face more challenging neurological issues despite treatment. The long-term quality of life can vary widely depending on the specific genetic changes and level of enzyme activity.

Current research on GTP cyclohydrolase I deficiency aims to better understand the wide range of clinical symptoms seen in this condition. Studies are investigating how different changes in enzyme activity contribute to the varying severity of symptoms. This research may help improve diagnostic methods and lead to better treatment options in the future.