Exacerbation of myopathy triggered by antiobesity drugs in a patient with multiple acyl-CoA dehydrogenase deficiency

Lin, Po-Yu; Liang, W.; Liao, Wei; Sun, Yuan

doi:10.1186/s12883-021-02121-y

Cited by 6 publications

(3 citation statements)

References 8 publications

(4 reference statements)

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“…Metabolic stress, such as high fat diet, excessive physical training, and using anti-obesity drugs, is essential to the disease onset, which works possibly by increasing the activity of fatty acid β-oxidation [7,10,30] and the subsequent increase in production of reactive oxygen species (ROS) [31,32]. We hypothesize that the effects of gender on late-onset MADD is mediated by sex differences in fat metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…The homozygous knock-in mice (Etfdh (h)A84T / (h)A84T ), as a model of late-onset MADD, developed the disease, only when fed by ribo avin de ciency and high fat diet [5]. Moreover, metabolic stress is essential to the disease onset, such as cold, excessive physical training, infection, fasting, and using antiobesity drugs [2,5,[7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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The male-to-female ratio in late-onset multiple acyl-CoA dehydrogenase deficiency: a systematic review and meta-analysis

Ma,

Zhang,

Liang

et al. 2023

Preprint

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Background: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common lipid storage myopathy. There are sex differences in fat metabolism and it is not known whether late-onset MADD affects men and women equally. Methods: In this systematic review and meta-analysis, the PubMed, Embase, Web of Science, CNKI, CBM, and Wanfang databases were searched until 01/08/2023. Studies reporting sex distribution in patients with late-onset MADD were included. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. Pre-specified outcomes of interest were the male-to-female ratio (MFR) of patients with late-onset MADD, the differences of clinical characteristics between the sexes, and factors influencing the MFR. Results: Of 3379 identified studies, 34 met inclusion criteria, yielding a total of 609 late-onset MADD patients. The overall pooled percentage of males was 58% (95% CI, 54%-63%) with low heterogeneity between studies (I2 = 2.99%; P = 0.42). The mean onset ages, diagnostic delay, and serum creatine kinase (CK), and allelic frequencies of 3 hotspot variants in ETFDH gene were similar between male and female patients (P > 0.05). Meta-regressions revealed that ethnic group was associated with the MFR in late-onset MADD, and subgroup meta-analyses demonstrated that East-Asian patients had a higher percentage of male, lower CK, and higher proportion of hotspot variants in ETFDH gene than non-East-Asian patients (P < 0.05). Conclusions: Male patients with late-onset MADD were more common than female patients. Ethnic was proved to be a factor influencing the MFR in late-onset MADD. These findings have implications for that male sex may be a risk factor for the disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The male-to-female ratio in late-onset multiple acyl-CoA dehydrogenase deficiency: a systematic review and meta-analysis

Ma,

Zhang,

Liang

et al. 2023

Preprint

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“…Intriguingly, a number of medications have been associated with adult-onset riboflavin-responsive diseases (Box 1 ). For example, drugs such as metformin, valproate and anti-viral drugs have been reported as inducing metabolic decompensation that can be at least partially mitigated by riboflavin therapy [ 97 , 98 ]. Importantly, these drugs have been identified as inducing mitochondrial toxicity in some patients possibly leading to impaired utilization of FAD and oxidative phosphorylation [ 99 , 100 ].…”

Section: Mechanisms Of Riboflavin Responsiveness In Adult-onset Diseasementioning

confidence: 99%

New insights into the nutritional genomics of adult-onset riboflavin-responsive diseases

Murgia,

Dehlia,

Guthridge

2023

Nutr Metab (Lond)

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Riboflavin, or vitamin B2, is an essential nutrient that serves as a precursor to flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). The binding of the FAD and/or FMN cofactors to flavoproteins is critical for regulating their assembly and activity. There are over 90 proteins in the human flavoproteome that regulate a diverse array of biochemical pathways including mitochondrial metabolism, riboflavin transport, ubiquinone and FAD synthesis, antioxidant signalling, one-carbon metabolism, nitric oxide signalling and peroxisome oxidative metabolism. The identification of patients with genetic variants in flavoprotein genes that lead to adult-onset pathologies remains a major diagnostic challenge. However, once identified, many patients with adult-onset inborn errors of metabolism demonstrate remarkable responses to riboflavin therapy. We review the structure:function relationships of mutant flavoproteins and propose new mechanistic insights into adult-onset riboflavin-responsive pathologies and metabolic dysregulations that apply to multiple biochemical pathways. We further address the vexing issue of how the inheritance of genetic variants in flavoprotein genes leads to an adult-onset disease with complex symptomologies and varying severities. We also propose a broad clinical framework that may not only improve the current diagnostic rates, but also facilitate a personalized approach to riboflavin therapy that is low cost, safe and lead to transformative outcomes in many patients.

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

Sunebo,

Appelqvist,

Häggqvist

et al. 2024

Annals of Neurology

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ObjectiveMultiple 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.MethodsWe 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.ResultsWe 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.InterpretationOur 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

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Exacerbation of myopathy triggered by antiobesity drugs in a patient with multiple acyl-CoA dehydrogenase deficiency

Cited by 6 publications

References 8 publications

The male-to-female ratio in late-onset multiple acyl-CoA dehydrogenase deficiency: a systematic review and meta-analysis

The male-to-female ratio in late-onset multiple acyl-CoA dehydrogenase deficiency: a systematic review and meta-analysis

New insights into the nutritional genomics of adult-onset riboflavin-responsive diseases

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

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