Late-onset multiple acyl-CoA dehydrogenase deficiency with breast cancer

Abstract Background Multiple acyl-CoA dehydrogenase deficiency (MAAD) is a rare metabolic disorder resulting from an abnormality in fatty acid oxidation. There are three types of presentations: neonatal onset with or without congenital anomalies and the late-onset type. There is much clinical heterogeneity in the presentation of late-onset variants; hence, the diagnosis is often delayed or missed. Case presentation Here, we report the successful management of a 41-year-old female with late-onset MAAD due to mutation in the ETFDH gene who presented with carcinoma of the breast. Chemotherapy was challenging because there were no previous reports regarding the treatment of such cases. Conclusion The diagnosis was made based on metabolic workup and gene mutation analysis. Unplanned surgery and chemotherapy can be fatal in these patients due to metabolic complications. With proper precautions and monitoring, the patient tolerated surgery and chemotherapy without any complications.

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Late-onset multiple acyl-CoA dehydrogenase deficiency mimicking myositis in an elderly patient: a case report

BMC Neurology ◽

10.1186/s12883-020-02010-w ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Yiming Zheng ◽

Yawen Zhao ◽

Wei Zhang ◽

Zhaoxia Wang ◽

Yun Yuan

Keyword(s):

Elderly Patient ◽

Muscle Weakness ◽

Dehydrogenase Deficiency ◽

Late Onset ◽

Lipid Storage ◽

Exercise Intolerance ◽

Lipid Storage Myopathy ◽

Case Presentation ◽

Acylcarnitine Profile ◽

Progressive Weakness

Abstract Background Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare and treatable inherited lipid storage myopathy. Here, we report an elderly patient with MADD mimicking myositis. Case presentation An 80-year-old woman had progressive weakness in her limbs, exercise intolerance, and no muscle pain for 3 months. The patient’s serum creatine kinase level was slightly elevated. The initial diagnosis was myositis. However, muscle biopsy showed many cytoplasmic vacuoles stained with oil red O, indicating the presence of lipid storage myopathy. The plasma acylcarnitine profile showed increased medium-chain and long-chain acylcarnitine species, consistent with the diagnosis of MADD. Riboflavin treatment dramatically improved muscle weakness. Conclusions MADD should be considered when evaluating elderly patients with subacute muscle weakness.

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Multiple Acyl-CoA Dehydrogenase Deficiency with Variable Presentation Due to a Homozygous Mutation in a Bedouin Tribe

Genes ◽

10.3390/genes12081140 ◽

2021 ◽

Vol 12 (8) ◽

pp. 1140

Author(s):

Orna Staretz-Chacham ◽

Shirly Amar ◽

Shlomo Almashanu ◽

Ben Pode-Shakked ◽

Ann Saada ◽

...

Keyword(s):

Electron Transfer ◽

Newborn Screening ◽

Dehydrogenase Deficiency ◽

Late Onset ◽

Acid Oxidation ◽

Homozygous Mutation ◽

Electron Transfer Flavoprotein ◽

The Difference ◽

Fad Binding ◽

Genotype Correlation

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a fatty acid and amino acid oxidation defect caused by a deficiency of the electron-transfer flavoprotein (ETF) or the electron-transfer flavoprotein dehydrogenase (ETFDH). There are three phenotypes of the disease, two neonatal forms and one late-onset. Previous studies have suggested that there is a phenotype–genotype correlation. We report on six patients from a single Bedouin tribe, five of whom were sequenced and found to be homozygous to the same variant in the ETFDH gene, with variable severity and age of presentation. The variant, NM_004453.3 (ETFDH): c.524G>A, p.(R175H), was previously recognized as pathogenic, although it has not been reported in the literature in a homozygous state before. R175H is located near the FAD binding site, likely affecting the affinity of FAD for EFT:QO. The single homozygous ETFDH pathogenic variant was found to be causing MADD in this cohort with an unexpectedly variable severity of presentation. The difference in severity could partly be explained by early diagnosis via newborn screening and early treatment with the FAD precursor riboflavin, highlighting the importance of early detection by newborn screening.

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

BMC Neurology ◽

10.1186/s12883-021-02121-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Po-Yu Lin ◽

Wen-Chen Liang ◽

Wei-An Liao ◽

Yuan-Ting Sun

Keyword(s):

Dehydrogenase Deficiency ◽

Acid Oxidation ◽

Prolonged Fasting ◽

Lipid Metabolism Disorder ◽

Oxidation Activity ◽

Case Presentation ◽

Metabolism Disorder ◽

Metabolic Crisis ◽

Taiwanese Woman ◽

Antiobesity Drugs

Abstract Background Multiple acyl-CoA dehydrogenase deficiency (MADD) is a treatable lipid metabolism disorder that presents as myopathy and episodic metabolic crisis. The metabolic crisis is typically associated with prolonged fasting or physical stress; however, the mechanism of metabolic crisis is not yet fully understood. Case presentation A 28-year-old Taiwanese woman presented with dyspnoea, poor appetite, and muscle weakness after using antiobesity drugs, including metformin, triiodothyronine, and topiramate. MADD was diagnosed, and her symptoms rapidly improved after treatment with riboflavin, carnitine, and ubiquinone. To date, antiobesity drugs have not been reported to be a provoking factor in fatty acid oxidation disorder. Conclusions The increase of β-oxidation activity due to antiobesity drugs supports the hypothetical substrate competition model for MADD metabolic crisis. Because the drugs our patient used are commonly prescribed, we report this case to increase the vigilance and proactivity of clinicians in recognising this treatable adult-onset myopathy.

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Successful management of refractory hypertension with dual calcium channel blocker therapy: case presentation

Archives of Family Medicine ◽

10.1001/archfami.6.5.503 ◽

1997 ◽

Vol 6 (5) ◽

pp. 503-505

Author(s):

K. Geurian

Keyword(s):

Calcium Channel ◽

Calcium Channel Blocker ◽

Channel Blocker ◽

Successful Management ◽

Refractory Hypertension ◽

Case Presentation ◽

Blocker Therapy

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An Obscure Colon Dilatation and its Underlying Cause: Case Report and Literature Review

10.31487/j.gscr.2020.01.03 ◽

2020 ◽

pp. 1-5

Author(s):

Anton Stift ◽

Kerstin Wimmer ◽

Felix Harpain ◽

Katharina Wöran ◽

Thomas Mang ◽

...

Keyword(s):

Case Report ◽

Sigmoid Colon ◽

Immunohistochemical Staining ◽

Late Onset ◽

Hirschsprung Disease ◽

Endoscopic Examination ◽

Case Presentation ◽

Idiopathic Megacolon ◽

History Of ◽

Cells Of Cajal

Introduction: Congenital as well as acquired diseases may be responsible for the development of a megacolon. In adult patients, Clostridium difficile associated infection as well as late-onset of Morbus Hirschsprung disease are known to cause a megacolon. In addition, malignant as well as benign colorectal strictures may lead to intestinal dilatation. In case of an idiopathic megacolon, the underlying cause remains unclear. Case Presentation: We describe the case of a 44-year-old male patient suffering from a long history of chronic constipation. He presented himself with an obscurely dilated large intestine with bowel loops up to 17 centimeters in diameter. Radiological as well as endoscopic examination gave evidence of a spastic process in the sigmoid colon. The patient was treated with a subtotal colectomy and the intraoperative findings revealed a stenotic stricture in the sigmoid colon. Since the histological examination did not find a conclusive reason for the functional stenosis, an immunohistochemical staining was advised. This showed a decrease in interstitial cells of Cajal (ICC) in the stenotic part of the sigmoid colon. Discussion: This case report describes a patient with an idiopathic megacolon, where the underlying cause remained unclear until an immunohistochemical staining of the stenotic colon showed a substantial decrease of ICCs. Various pathologies leading to a megacolon are reviewed and discussed.

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Newborn screening and molecular features of patients with multiple acyl-CoA dehydrogenase deficiency in Quanzhou, China

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0694 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Yiming Lin ◽

Weifeng Zhang ◽

Zhixu Chen ◽

Chunmei Lin ◽

Weihua Lin ◽

...

Keyword(s):

Mass Spectrometry ◽

Genetic Analysis ◽

Tandem Mass Spectrometry ◽

Newborn Screening ◽

Dehydrogenase Deficiency ◽

Late Onset ◽

False Negative ◽

Tandem Mass ◽

Lipid Storage Myopathy ◽

Molecular Features

Abstract Objectives Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid, amino acid and choline metabolism. Late-onset MADD is caused by ETFDH mutations and is the most common lipid storage myopathy in China. However, few patients with MADD have been identified through newborn screening (NBS). This study assessed the acylcarnitine profiles and molecular features of patients with MADD identified through NBS. Methods From January 2014 to June 2020, 479,786 newborns screened via tandem mass spectrometry were recruited for this study. Newborns with elevated levels of multiple acylcarnitines were recalled, those who tested positive in the reassessment were referred for genetic analysis. Results Of 479,786 newborns screened, six were diagnosed with MADD. The MADD incidence in the Chinese population was estimated to be 1:79,964. Initial NBS revealed five patients with typical elevations in the levels of multiple acylcarnitines; however, in one patient, acylcarnitine levels were in the normal reference range during recall. Notably, one patient only exhibited a mildly increased isovalerylcarnitine (C5) level at NBS. The patient with an atypical acylcarnitine profile was diagnosed with MADD by targeted gene sequencing. Six distinct ETFDH missense variants were identified, with the most common variant being c.250G>A (p.A84T), with an allelic frequency of 58.35 (7/12). Conclusions These findings revealed that it is easy for patients with MADD to go unidentified, as they may have atypical acylcarnitine profiles at NBS and the recall stage, indicating the value of genetic analysis for confirming suspected inherited metabolic disorders in the NBS program. Therefore, false-negative (FN) results may be reduced by combining tandem mass spectrometry (MS/MS) with genetic testing in NBS for MADD.

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