背景:由6-丙酮酸四氢蝶呤合酶(PTPS)缺乏症引起的四氢生物蝶呤(BH4)缺乏症是一种罕见的疾病,是台湾高苯丙氨酸血症的主要原因之一。
方法:在本研究中,我们回顾了12例PTPS缺乏的青少年和成人患者(7例女性和5例男性)的临床病程.
结果:患者在诊断后不久通过BH4,左旋多巴/卡比多巴的组合进行新生儿筛查,和5-OH-色氨酸.他们的血浆苯丙氨酸和酪氨酸水平得到了很好的控制,治疗后其催乳素水平也有所下降。然而,随着他们进入青春期,他们的催乳素水平逐渐上升,当前年龄为27.5[四分位数间距(IQR7.9)]岁,12例患者中有5例催乳素水平高度升高(一名男性患者>100ng/mL,正常参考值,男性<11ng/mL,女性<17ng/mL)或症状,包括月经不调,闭经,和乳房肿胀(四名女性患者)。这5例患者的左旋多巴剂量(14.3(IQR3.0)mg/kg/天)略高于其他患者(p=0.05)。磁共振成像研究未显示垂体前叶大小的增加,尽管在一名患者中发现了Rathke裂隙囊肿。两名患者接受了卡麦角林治疗,迅速降低催乳素水平,缓解症状。
结论:高催乳素血症常见于PTPS缺乏的女性患者,尤其是青春期之后.长效多巴胺激动剂,如卡麦角林,可能是大多数BH4缺乏症患者的必要辅助治疗。
BACKGROUND: Tetrahydrobiopterin (BH4) deficiency caused by 6-pyruvoyl-tetrahydropterin synthase (
PTPS) deficiency is a rare disorder that is one of the major causes of hyperphenylalaninemia in Taiwan.
METHODS: In this study, we reviewed the clinical courses of 12 adolescent and adult patients (7 females and 5 males) with
PTPS deficiency.
RESULTS: The patients were treated shortly after diagnosis through newborn screening with a combination of BH4, levodopa/carbidopa, and 5-OH-tryptophan. Their plasma phenylalanine and tyrosine levels were well controlled, and their prolactin levels were also decreased after treatment. However, their prolactin levels gradually rose as they grew into puberty, and at a current age of 27.5 [interquartile range (IQR 7.9)] years, five of the 12 patients had either highly elevated prolactin levels (> 100 ng/mL in one male patient, normal reference values, male < 11 ng/mL, female < 17 ng/mL) or symptoms, including irregular menstruation, amenorrhea, and breast swelling (in four female patients). The dosage of levodopa in these five patients (14.3 (IQR 3.0) mg/kg/day) was slightly higher than that in the other patients (p = 0.05). Magnetic resonance imaging studies did not reveal an increase in the size of the anterior pituitary gland, although a Rathke cleft cyst was found in one patient. Two patients received cabergoline treatment, which promptly lowered prolactin levels and relieved symptoms.
CONCLUSIONS: Hyperprolactinemia is common in female patients with
PTPS deficiency, especially after puberty. A long-acting dopamine agonist, such as cabergoline, may be a necessary adjunctive treatment for most patients with BH4 deficiency.