Pre- and postnatal diagnosis of tyrosine hydroxylase deficiency

Tyrosine hydroxylase (TH) is a key enzyme in the biosynthesis of dopamine, epinephrine and norepinephrine. The primary diagnosis of TH deficiency is based on the measurement of neurotransmitter metabolites and pterins in the cerebrospinal fluid, and the final diagnosis is made by detection of mutations in the TH gene. The clinical expression varies with presentations as infantile parkinsonism, L-dopa responsive spastic paraplegia, or as a progressive severe encephalopathy. Treatment with L-dopa is not always sufficient and a number of patients with poor or no response to L-dopa have recently been described.

TH is not expressed in amniotic fluid cells or in chorionic villus, so prenatal diagnosis by measurement of the enzyme activity is not possible. The only possibility of a prenatal diagnosis is by analyzing the TH gene for mutations.

Here we describe a case of severe TH deficiency, identification of two novel mutations (p.R328W and p.T399M) and most importantly, the first prenatal diagnosis of this disease.

The availability of prenatal diagnosis offers the parents new options. They may use the result as preparation for the birth of a child with TH deficiency, or they may decide termination of an affected pregnancy.