A young woman with persistent hypoglycemia, rhabdomyolysis, and coma: Recognizing fatty acid oxidation defects in adults

Kluge, Stefan; Kühnelt, P.; Block, Andreas; Merkel, Martin; Gocht, Andreas; Lukács, Zoltán; Kohlschütter, Alfried; Kreymann, G.

doi:10.1097/01.ccm.0000045201.10682.f6

Cited by 27 publications

(14 citation statements)

References 10 publications

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“…The cardiac symptoms are currently believed to arise from an energy deficit due to impaired ␤-oxidation of LCFAs (which normally supply ϳ70% of energy to the normal beating heart) and/or accumulation of toxic metabolites, such as long-chain (LC)-acylcarnitines or LC-CoAs (6). In the most severe cases, without appropriate treatments, VLCAD-deficient infants will succumb from sudden cardiac death, mainly caused by severe arrhythmias between 2 and 5 mo of age, often after fasting or an infectious illness (30,47,57). However, ϳ30% of these patients never develop cardiac symptoms and display a milder clinical phenotype characterized by hypoketotic hypoglycemia, indicating metabolic derangements in the liver (57).…”

mentioning

confidence: 99%

Prolonged QT interval and lipid alterations beyond β-oxidation in very long-chain acyl-CoA dehydrogenase null mouse hearts

Gélinas

Thompson-Legault

Bouchard

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency frequently present cardiomyopathy and heartbeat disorders. However, the underlying factors, which may be of cardiac or extra cardiac origins, remain to be elucidated. In this study, we tested for metabolic and functional alterations in the heart from 3- and 7-mo-old VLCAD null mice and their littermate counterparts, using validated experimental paradigms, namely, 1) ex vivo perfusion in working mode, with concomitant evaluation of myocardial contractility and metabolic fluxes using (13)C-labeled substrates under various conditions; as well as 2) in vivo targeted lipidomics, gene expression analysis as well as electrocardiogram monitoring by telemetry in mice fed various diets. Unexpectedly, when perfused ex vivo, working VLCAD null mouse hearts maintained values similar to those of the controls for functional parameters and for the contribution of exogenous palmitate to β-oxidation (energy production), even at high palmitate concentration (1 mM) and increased energy demand (with 1 μM epinephrine) or after fasting. However, in vivo, these hearts displayed a prolonged rate-corrected QT (QTc) interval under all conditions examined, as well as the following lipid alterations: 1) age- and condition-dependent accumulation of triglycerides, and 2) 20% lower docosahexaenoic acid (an omega-3 polyunsaturated fatty acid) in membrane phospholipids. The latter was independent of liver but affected by feeding a diet enriched in saturated fat (exacerbated) or fish oil (attenuated). Our finding of a longer QTc interval in VLCAD null mice appears to be most relevant given that such condition increases the risk of sudden cardiac death.

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mentioning

confidence: 99%

Prolonged QT interval and lipid alterations beyond β-oxidation in very long-chain acyl-CoA dehydrogenase null mouse hearts

Gélinas

Thompson-Legault

Bouchard

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…These cases show that a revelation of MCAD deficiency in adulthood (between 16 and 45 years of age) by a very severe acute clinical presentation associated with arrhythmia is possible. Adult (32 year-old) presentation of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency with cardiomyopathy, hypoglycemia, and rhabdomyolysis highlights a potential risk of cardiac complications even in adults [27]. The main problem is that fatty-acid metabolism disorders are the most difficult to identify because of the transient nature of clinical and biological manifestations [26].…”

Section: Discussionmentioning

confidence: 99%

Inherited Metabolic Diseases and Cardiac Pathology in Adults: Diagnosis and Prevalence in a CardioMetabo Study

Braïlova

Clerfond

Trésorier

et al. 2020

JCM

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Many inherited metabolic diseases (IMD) have cardiac manifestations. The aim of this study was to estimate the prevalence of IMD in adult patients with hypertrophic cardiomyopathy (HCM) and cardiac rhythm abnormalities that require cardiac implantable electronic devices (CIEDs). The study included a review of the medical files of patients aged 18 to 65 years who were followed in our cardiology department during the period 2010-2017. Metabolic explorations for Fabry disease (FD), mitochondrial cytopathies, and fatty-acid metabolism disorders were carried out in patients with unexplained etiology. The prevalence of IMD in patients with HCM was 5.6% (confidence interval (CI): 2.6-11.6). Six cases of IMD were identified: 1 mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, 1 Hurler syndrome, 2 Friedreich's ataxia, 1 FD, and 1 short-chain acyl-CoA dehydrogenase deficiency. Three cases of IMD were identified in patients requiring CIEDs: 1 patient with Leber hereditary optic neuropathy, 1 FD, and 1 short chain acyl-CoA dehydrogenase (SCAD) deficiency. IMD prevalence in patients with CIEDs was 3.1% (CI: 1.1-8.8). IMD evaluation should be performed in unexplained HCM and cardiac rhythm abnormalities adult patients, since the prevalence of IMD is relatively important and they could benefit from specific treatment and family diagnosis.

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“…Az összes, szűréssel kiemelt zsírsav-oxidációs zavar születéskori incidenciája 10/100 000 körülire becsülhető, leggyakoribb formája a közepes szénláncú acil-CoA-dehidrogenáz-deficientia (MCAD), amely az összes eset közel 50%-a, egyenként háromszor-tízszer ritkább a többi szűrt forma [22]. Minden gyakoribb betegség esetében közöltek felnőtt-kori eseteket is [23][24][25][26]. Magyarországon, a két szűrő-központ (Semmelweis Egyetem I. Gyermekgyógyászati Klinika és Szegedi Tudományegyetem Gyermekgyógyá-szati Klinika) országos adatai alapján az incidencia megegyezik a nemzetközi adatokkal.…”

Section: A Zsírsavoxidáció Zavaraiunclassified

Rhabdomyolysis – Mikor vessük fel metabolikus myopathia lehetőségét? Esetismertetés és diagnosztikus algoritmus

et al. 2017

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Rekurráló rhabdomyolysis miatt kezelt 46 éves nő esetét ismertetjük. Betegünknél a metabolikus myopathia hátteré-ben a zsírsav-oxidáció veleszületett zavarát, hosszú szénláncú acil-koenzim A-dehidrogenáz-hiányt diagnosztizáltunk, miután kóros acil-karnitin-és vizeletszervessav-profilt, valamint alacsony residualis enzimaktivitást detektáltunk, vé-gül genetikai vizsgálattal patogén eltérést igazoltunk. A dietoterápia bevezetése után sem kórházi kezelést igénylő metabolikus krízis nem fordult elő, sem myopathia nem alakult ki. Az eset kapcsán áttekintjük a rhabdomyolysis és a terhelés utáni izompanaszok differenciáldiagnosztikáját, különös tekintettel a metabolikus myopathiákra. Kiemeljük a zsírsav-oxidációs zavarok jellegzetességeit, illetve a hosszú szénláncú zsírsav-oxidációs zavarok akut ellátásának és gondozásának alapelveit. A metabolikus myopathiák csoportjába tartozó betegségek jól kezelhetőek, és a betegek számára megfelelő életminőséget biztosíthatunk, azonban az elsősorban zsírsav-oxidációs zavarokra jellemző, gyorsan kialakuló metabolikus krízis súlyos, akár halálos kimenetelű is lehet. Több, ebbe a csoportba tartozó betegség szerepel az újszülöttkorban szűrt anyagcsere-betegségek között, azonban esetünk ismertetésével is szeretnénk felhív-ni a figyelmet arra, hogy egyes esetekben az első tünetek csak felnőttkorban jelentkeznek. Ismétlődő rhabdomyolysis esetén bármely korú betegnél fel kell vetni az öröklődő anyagcserezavar lehetőségét. Orv Hetil. 2017; 158(47): 1873-1882. Kulcsszavak: rhabdomyolysis, zsírsav-oxidációs zavar, VLCAD-deficientia, izomanyagcsere Rhabdomyolysis -may it be a metabolic myopathy? Case report and diagnostic algorithmWe report the case of a 46-year-old female patient with recurrent rhabdomyolysis. In the background of her metabolic myopathy an inherited metabolic disorder of the fatty acid oxidation, very long-chain acyl-coenzyme A-dehydrogenase deficiency was diagnosed. The diagnosis was based on abnormal acyl-carnitine-and urine organic-acid profile in addition to low residual enzyme activity, and was confirmed by genetic testing. After introduction of dietotherapy metabolic crisis necessitating hospital admission has not occurred neither have fixed myopathic changes developed. We present here the differential diagnosis of rhabdomyolysis and exertional muscle complaints, with the metabolic myopathies in focus. The main features of fatty acid oxidation disorders are highlighted, acute and chronic managements of very long-chain acyl-coenzyme A-dehydrogenase deficiency are discussed. Metabolic myopathies respond well to treatment, so good quality of life can be achieved. However, especially in fatty acid oxidation disorders, a metabolic crisis may develop quickly and can be fatal, albeit rarely. Some of these disorders can be identified by newborn screening, but occasionally the symptoms may manifest only in adulthood.

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A young woman with persistent hypoglycemia, rhabdomyolysis, and coma: Recognizing fatty acid oxidation defects in adults

Abstract: Genetic defects of fatty acid oxidation should be suspected, even in previously healthy adults, when typical symptoms such as nonketotic hypoglycemia, rhabdomyolysis, cardiomyopathy, or unexplained organ steatosis point to such a disorder of energy metabolism.

Cited by 27 publications

References 10 publications

Prolonged QT interval and lipid alterations beyond β-oxidation in very long-chain acyl-CoA dehydrogenase null mouse hearts

Prolonged QT interval and lipid alterations beyond β-oxidation in very long-chain acyl-CoA dehydrogenase null mouse hearts

Inherited Metabolic Diseases and Cardiac Pathology in Adults: Diagnosis and Prevalence in a CardioMetabo Study

Rhabdomyolysis – Mikor vessük fel metabolikus myopathia lehetőségét? Esetismertetés és diagnosztikus algoritmus

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