Multiple Acyl-Coenzyme A Dehydrogenase Deficiency Is Associated with Sertraline Use – Is There an Acquired Form?

IF 8.1 1区 医学 Q1 CLINICAL NEUROLOGY Annals of Neurology Pub Date : 2024-08-02 DOI:10.1002/ana.27030
Sofie Sunebo MD, Hanna Appelqvist PhD, Bo Häggqvist PhD, Olof Danielsson MD, PhD
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Abstract

Objective

Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a disorder of fatty acid oxidation and considered an inborn error of metabolism. In recent years, we have diagnosed an increasing number of patients where, despite extensive investigation, no disease-causing mutations have been found. We therefore investigated a cohort of consecutive patients, with the objective to detect possible non-genetic causes.

Methods

We searched the patient records and the registry of muscle biopsies, for patients with MADD, diagnosed within the past 10 years. The patient records were reviewed regarding symptoms, clinical findings, comorbidities, drugs, diagnostic investigations, and response to treatment. In addition, complementary investigations of muscle tissue were performed.

Results

We identified 9 patients diagnosed with late-onset MADD. All presented with muscle weakness and elevated levels of creatine kinase. A lipid storage myopathy was evident in the muscle biopsies, as was elevated acylcarnitines in blood. Despite thorough genetic investigations, a probable genetic cause was found in only 2 patients. Remarkably, all 7 patients without disease-causing mutations were treated with sertraline. In some cases, a deterioration of symptoms closely followed dose increase, and discontinuation resulted in an improved acylcarnitine profile. All 9 patients responded to riboflavin treatment with normalization of creatine kinase and muscle biopsy findings, and in 8 patients the clinical symptoms clearly improved.

Interpretation

Our findings strongly suggest that sertraline may induce an acquired form of MADD in some patients. Importantly, riboflavin treatment seems to be similarly effective as in genetic MADD, but discontinuation of sertraline is reasonably warranted. ANN NEUROL 2024;96:802–811

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多酰辅酶 A 脱氢酶缺乏症与舍曲林的使用有关--是否存在后天获得的形式?
目的:多酰基辅酶 A 脱氢酶缺乏症(MADD)是一种脂肪酸氧化障碍,被认为是一种先天性代谢错误。近年来,我们诊断出越来越多的患者,尽管进行了广泛的调查,但仍未发现致病突变。因此,我们对一组连续患者进行了调查,目的是发现可能的非遗传原因:我们搜索了过去 10 年内确诊的 MADD 患者的病历和肌肉活检登记。我们查阅了患者的病历,包括症状、临床表现、合并症、药物、诊断检查和治疗反应。此外,还对肌肉组织进行了辅助检查:结果:我们发现了 9 名被诊断为晚发性 MADD 的患者。所有患者均表现为肌无力和肌酸激酶水平升高。在肌肉活检中发现了明显的脂质贮积性肌病,血液中的酰基肉碱也有所升高。尽管进行了全面的遗传学调查,但只有两名患者找到了可能的遗传原因。值得注意的是,所有 7 名没有致病基因突变的患者都接受了舍曲林治疗。在某些病例中,剂量增加后症状会随之恶化,停药后酰基肉碱状况会得到改善。所有 9 名患者对核黄素治疗均有反应,肌酸激酶和肌肉活检结果均恢复正常,其中 8 名患者的临床症状明显改善:我们的研究结果有力地表明,舍曲林可能会诱发某些患者的获得性MADD。重要的是,核黄素治疗似乎与遗传性 MADD 相似有效,但停用舍曲林是合理的。ann neurol 2024.
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来源期刊
Annals of Neurology
Annals of Neurology 医学-临床神经学
CiteScore
18.00
自引率
1.80%
发文量
270
审稿时长
3-8 weeks
期刊介绍: Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
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