Escuela de Doctorado, Universidad Católica de Valencia San Vicente Mártir, 46001 Valencia, Spain.
Department of Pathology, School of Health Sciences, Universidad Católica de Valencia San Vicente Mártir, 46001 Valencia, Spain.
Int J Mol Sci. 2024 Jul 16;25(14):7778. doi: 10.3390/ijms25147778.
Chronic fatigue syndrome (CFS) is a heterogeneous disorder with a genetically associated vulnerability of the catecholamine metabolism (e.g., catechol O-methyltransferase polymorphisms), in which environmental factors have an important impact. Alpha-methyl-p-tyrosine (AMPT; also referred to as metyrosine) is an approved medication for the treatment of pheochromocytoma. As a tyrosine hydroxylase inhibitor, AMPT may be a potential candidate for the treatment of diseases involving catecholamine alterations. However, only small-scale clinical trials have tested AMPT repurposing in a few other illnesses. The current case report compiles genetic and longitudinal biochemical data for over a year of follow-up of a male patient sequentially diagnosed with sustained overstress, neurasthenia, CFS (diagnosed in 2012 as per the Center for Disease Control (CDC/Fukuda)), and postural orthostatic tachycardia syndrome (POTS) over a 10-year period and reports the patient's symptom improvement in response to low-medium doses of AMPT. This case was recognized as a stress-related CFS case. Data are reported from medical records provided by the patient to allow a detailed response to treatment targeting the hyperadrenergic state presented by the patient. We highlight the lack of a positive response to classical approaches to treating CFS, reflecting the limitations of CFS diagnosis and available treatments to alleviate patients' symptoms. The current pathomechanism hypothesis emphasizes monoamine alterations (hyperadrenergic state) in the DA/adrenergic system and a dysfunctional autonomic nervous system resulting from sympathetic overactivity. The response of the patient to AMPT treatment highlights the relevance of pacing with regard to stressful situations and increased activity. Importantly, the results do not indicate causality between AMPT and its action on the monoamine system, and future studies should evaluate the implications of other targets.
慢性疲劳综合征（CFS）是一种异质性疾病，其儿茶酚胺代谢存在遗传相关的脆弱性（例如，儿茶酚-O-甲基转移酶多态性），其中环境因素具有重要影响。α-甲基-对酪氨酸（AMPT；也称为甲硫氨酸）是一种已批准用于治疗嗜铬细胞瘤的药物。作为一种酪氨酸羟化酶抑制剂，AMPT 可能是治疗涉及儿茶酚胺改变的疾病的潜在候选药物。然而，只有小规模的临床试验已经测试了 AMPT 在其他几种疾病中的再利用。本病例报告综合了一名男性患者的遗传和纵向生化数据，该患者在 10 年内先后被诊断为持续性过度应激、神经衰弱、CFS（根据疾病控制和预防中心（CDC/Fukuda）于 2012 年诊断）和体位性心动过速综合征（POTS），并进行了超过一年的随访。报告了患者对低-中剂量 AMPT 的症状改善，并报告了患者对低-中剂量 AMPT 的症状改善。该病例被认为是与应激相关的 CFS 病例。数据来自患者提供的病历，以允许针对患者呈现的高肾上腺素状态进行详细的治疗反应。我们强调了对 CFS 经典治疗方法缺乏积极反应，反映了 CFS 诊断和现有治疗方法缓解患者症状的局限性。目前的发病机制假说强调单胺改变（高肾上腺素状态）在 DA/肾上腺素能系统和交感神经过度活跃导致的自主神经功能障碍。患者对 AMPT 治疗的反应突出了与应激情况和活动增加有关的起搏的重要性。重要的是，结果并不表明 AMPT 与其在单胺系统上的作用之间存在因果关系，未来的研究应评估其他靶点的意义。
