Rare brain disorder is treatable

Tyrosine hydroxylase deficiency (THD) is a neurometabolic genetic disorder that has so far only been diagnosed in 50 people worldwide. The symptoms include motor and cognitive impairments, such as hypokinesia, bradykinesia and rigidity, often associated with Parkinson's disease. An international group of researchers, including one from Saint Joseph University in Lebanon, has assessed 36 cases of THD in the medical literature to better understand the condition.

The authors suggest dividing the disease into two phenotypes, namely Type A, which onsets within the first year of life and Type B, which is evident earlier in the first few months. They found the condition was almost exclusively caused by missense mutations in the tyrosine hydroxylase (TH) gene. The severity of symptoms was found to be related to a decrease in concentration of homovanillic acid (HVA) in the cerebrospinal fluid (CSF).

Diagnosis of THD is tricky since the symptoms overlap with other disorders. Therefore, clinical tests may not offer a conclusive result. Consequently, the group advocates diagnosis by screening for mutations in the TH gene, analysis of CSF, and looking at brain imagery.

The researchers stress that THD, which causes a deficiency in dopamine, is a severe syndrome, but is treatable if properly diagnosed. They endorse treatment through the administration of L-dopa, which plays a role in the formation of dopamine inside the body. The dose must be closely monitored, however, as many patients are hypersensitive to L-dopa. They should be started on minimal doses before gradually increasing levels until the patient responds to treatment. Those that tolerate L-dopa have demonstrated dramatic clinical improvement with the disappearance of disabling symptoms and no serious side effects for up to 30 years.

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