R233H mutation in patients with tyrosine hydroxylase deficiency and corresponding phenotypes: a study of four cases and literature review.

Owing to the small number of patients with tyrosine hydroxylase (TH) deficiency, no genotype-phenotype correlations have yet been identified. To investigate the genotype-phenotype correlation of R233H mutation in TH deficiency, we analyzed the clinical manifestations and treatment responses of four patients with the R233H homozygous mutation. Thirty-eight additional patients, available from the literature, known to be homozygous or heterozygous for the R233H mutation, were combined with the four cases from our hospital. Data for a total of 42 patients were retrieved. Our four patients showed clinical presentation consistent with Type A TH deficiency, and responded well to levodopa therapy, with an improvement in clinical symptoms within 1-2 weeks. In the 42 patients, 20 of 42 patients (48%) were homozygous and 22 (52%) were heterozygous for the R233H mutation. Of the 20 patients who were homozygous for the R233H mutation, a majority (80%) suffered from Type A TH deficiency. Of the 8 patients that were heterozygous for the R233H/the mutation located downstream of exon 11, 7 patients (86%) suffered from Type B TH deficiency. Of the 7 patients who were heterozygous for the R233H/nonsense mutation, 6 (86%) suffered from Type B TH deficiency. Genotype-phenotype correlation of R233H mutation was observed in TH deficiency. The homozygous R233H mutation frequently manifests as Type A TH deficiency, whereas R233H/nonsense mutation or any mutation located downstream of exon 11 manifests as Type B TH deficiency.