Department of Pediatrics, Beijing Tiantan Hospital, Capital Medical University, 100070 Beijing, China.
Outpatient Department, Beijing Children's Hospital, Capital Medical University, 100045 Beijing, China.
J Integr Neurosci. 2022 Jan 28;21(1):35. doi: 10.31083/j.jin2101035.
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.
由于酪氨酸羟化酶（TH）缺乏症患者数量较少，尚未确定基因型-表型相关性。为了研究 TH 缺乏症中 R233H 突变的基因型-表型相关性，我们分析了 4 例 R233H 纯合突变患者的临床表现和治疗反应。此外，我们还结合来自我们医院的 4 例患者，对文献中报道的 38 例已知为 R233H 突变纯合或杂合的患者进行了分析。共检索到 42 例患者的数据。我们的 4 例患者表现出与 A 型 TH 缺乏症一致的临床表现，对左旋多巴治疗反应良好，临床症状在 1-2 周内得到改善。在 42 例患者中，有 42 例（48%）为 R233H 突变纯合子，22 例（52%）为杂合子。在 20 例 R233H 突变纯合子患者中，大多数（80%）患有 A 型 TH 缺乏症。在 8 例携带突变位于外显子 11 下游的 R233H/杂合子患者中，有 7 例（86%）患有 B 型 TH 缺乏症。在 7 例携带 R233H/无义突变的杂合子患者中，有 6 例（86%）患有 B 型 TH 缺乏症。在 TH 缺乏症中观察到 R233H 突变的基因型-表型相关性。R233H 纯合突变常表现为 A 型 TH 缺乏症，而 R233H/无义突变或任何位于外显子 11 下游的突变则表现为 B 型 TH 缺乏症。
