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.

Age differences in clinical characteristics, health care, and outcomes after ischemic stroke in China.

BACKGROUND AND PURPOSE: Little information is available on the effects of age on health care and outcomes of ischemic stroke (IS) in China. Our aim was to evaluated risk factors, health care, and outcomes among age groups including ≤ 45, 46-65, 66-79, and ≥ 80 years and to find whether the outcome was affected by age and health care. METHODS: CNSR is a nationwide prospective registry for patients admitted with acute stroke and prospectively followed up 12-month outcomes. Demographics, socioeconomics, risk factors, health care, and outcomes were analyzed among age groups, and multivariate regression analysis was used to determine the association of outcome and age and health care. RESULTS: We identified 12,415 acute IS patients for analysis. Of 1179 (9.50%) were aged ≥ 80 years. In terms of risk factors, cardiac diseases were significantly more frequent in patients ≥ 80 years, behavioral risk factors were more common in younger patients, and hypertension, hyperlipidemia, and diabetes were more seen in 46-79 patients. The use of health care varied among groups and was significantly lower in ≥ 80 years especially in secondary prevention. The very old patients had the worst outcomes even after adjusting by prognostic factors; however, adjusting forward by health care, the extent of differences decreased. CONCLUSIONS: In CNSR, differences in stroke clinic characteristics and health care were observed among various age groups, and the old patients, receiving lower levels of stroke care, had the worst outcomes. Knowledge of the age differences in ischemic stroke may be helpful to appropriately allocate the limited health resources and to improve stroke outcomes.