Psychiatric manifestations in patients with tetrahydrobiopterin (BH4) defects are common, and may occur even with treatment of the underlying disorder. The neurobiological background of these conditions has been linked to abnormalities of neurotransmitters, such as dopamine, serotonin, norepinephrine, and gamma-aminobutyric acid. Here, we review the psychiatric profile of all patients with BH4 defects followed in the pediatric and adult metabolic clinics at our center. Three patients with autosomal recessive (AR) guanosine triphosphate cyclohydrolase (GTPCH) deficiency and three patients with 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency were reviewed.

All patients had behavioral disturbances and two had significant psychiatric comorbidities. These included attention deficit/hyperactivity disorder, anxiety, depression, aggression, or oppositional defiant disorder. One patient with PTPS deficiency had a severe psychiatric presentation, requiring inpatient admission and temporary placement into foster care for intensive behavioral therapy. Another with AR GTPCH deficiency was diagnosed with aggressive behavioral dysregulation requiring intensive psychiatric treatment. Management of the psychiatric manifestations of BH4 defects can be challenging, due to lack of information and studies of interactions between psychiatric medications on the deficient neurotransmitters and their receptors in these conditions. Further studies are needed to establish safety and efficacy of these treatments.

四氢生物蝶呤 (BH4) 缺陷患者的精神症状很常见，甚至在治疗基础疾病后也可能出现。这些病症的神经生物学背景与神经递质异常有关，例如多巴胺、血清素、去甲肾上腺素和γ-氨基丁酸。在这里，我们回顾了我们中心儿科和成人代谢诊所跟踪的所有 BH4 缺陷患者的精神病学概况。对三名常染色体隐性遗传 (AR) 三磷酸鸟苷环水解酶 (GTPCH) 缺乏症患者和三名 6-丙酮酰四氢蝶呤合酶 (PTPS) 缺乏症患者进行了回顾。

所有患者都有行为障碍，其中两人有明显的精神合并症。这些包括注意力缺陷/多动障碍、焦虑、抑郁、攻击性或对立违抗障碍。一名 PTPS 缺乏症患者有严重的精神症状，需要住院并暂时安置在寄养机构接受强化行为治疗。另一名患有 AR GTPCH 缺陷的患者被诊断为攻击性行为失调，需要强化精神治疗。由于缺乏关于精神科药物对这些情况下神经递质缺陷及其受体之间相互作用的信息和研究，BH4 缺陷精神科表现的管理可能具有挑战性。需要进一步的研究来确定这些治疗的安全性和有效性。