Tyrosine hydroxylase deficiency (THD) is a disorder affecting movement, causing uncontrollable muscle contractions, and leading to developmental delay. THD has a spectrum of symptoms, ranging from mild to very severe.
In the mild form of THD, symptoms usually start in childhood, manifesting initially in the feet or legs with jerky movements and progressing to physical rigidity. These symptoms are similar to those seen in Parkinson’s disease. Children with the mild form typically don’t have learning disabilities, but without treatment, they may lose the ability to walk over time. Early intervention can help prevent or alleviate many symptoms. The severe form of THD appears in infancy, with affected infants experiencing delayed motor skills, weakness in the chest and abdomen, stiffness in limbs, and tremors. These infants may face learning disabilities, speech problems, and behavioral issues. Some individuals with severe THD also have problems with their autonomic nervous system, which regulates unconscious bodily functions. Treatment for severe cases may take longer to show results, and the most severe cases may have limited success with treatment.
Individuals with the mild form of THD usually respond well to supplements of L-dopa and carbidopa, especially if taken before symptoms appear. Even if symptoms have begun, these children often respond well to the medication. For severe THD cases, treatment with L-dopa and carbidopa may improve motor skills over time, but the benefits may be less pronounced.
This group of conditions is caused by pathogenic (disease-causing) variants in the ABCC8 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background.
Other names for this condition are autosomal recessive infantile parkinsonism, Segawa syndrome, autosomal recessive, and TH-deficient DRD
Resources:
Pediatric Neurotransmitter Disease Association
Revised November 2023
