A Turkish Patient With Succinyl-CoA:3-Oxoacid CoA Transferase Deficiency Mimicking Diabetic Ketoacidosis

Erdol, Sahin; Türe, Mehmet; Yakut, Tahsin; Sağlam, Halil; Sasai, Hideo; Abdelkreem, Elsayed; Otsuka, Hiroki; Fukao, Toshiyuki

doi:10.1177/2326409816651281

Cited by 7 publications

(5 citation statements)

References 19 publications

(25 reference statements)

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“…SCOT insufficiency is a rare inborn error of metabolism characterized by either asymptotic or permanently ketotic intermittent ketoacidotic crises between episodes [203][204][205]. Clinically, ketoacidotic episodes are precipitated by acute infection, starvation, and fever or by the administration of protein under 24 months of age [203,205]. In accordance with this clinical observation, temperature sensitivity to the mutant protein has been recognized [206].…”

Section: Inherited Diseases In Which Ketosis Occursmentioning

confidence: 89%

“…Since then, several reports have been published on its occurrence [204,205]. SCOT insufficiency is a rare inborn error of metabolism characterized by either asymptotic or permanently ketotic intermittent ketoacidotic crises between episodes [203][204][205]. Clinically, ketoacidotic episodes are precipitated by acute infection, starvation, and fever or by the administration of protein under 24 months of age [203,205].…”

Section: Inherited Diseases In Which Ketosis Occursmentioning

confidence: 99%

“…Deficiency of mitochondrial succinyl-coA:3ketoacid coA transferase (SCOT) was first described in 1972 [203]. Since then, several reports have been published on its occurrence [204,205]. SCOT insufficiency is a rare inborn error of metabolism characterized by either asymptotic or permanently ketotic intermittent ketoacidotic crises between episodes [203][204][205].…”

Section: Inherited Diseases In Which Ketosis Occursmentioning

confidence: 99%

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Breath acetone as a potential marker in clinical practice

Ruzsányi

Kalapos²

2017

J. Breath Res.

121

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In recent decades, two facts have changed the opinion of researchers about the function of acetone in humans. Firstly, it has turned out that acetone cannot be regarded as simply a waste product of metabolism, because there are several pathways in which acetone is produced or broken down. Secondly, methods have emerged making possible its detection in exhaled breath, thereby offering an attractive alternative to investigation of blood and urine samples. From a clinical point of view the measurement of breath acetone levels is important, but there are limitations to its wide application. These limitations can be divided into two classes, technical and biological limits. The technical limits include the storage of samples, detection threshold, standardization of clinical settings, and the price of instruments. When considering the biological ranges of acetone, personal factors such as race, age, gender, weight, food consumption, medication, illicit drugs, and even profession/class have to be taken into account to use concentration information for disorders. In some diseases such as diabetes mellitus and lung cancer, as well as in nutrition-related behavior such as starvation and ketogenic diet, breath acetone has been extensively examined. At the same time, there is a lack of investigations in other cases in which ketosis is also evident, such as in alcoholism or an inborn error of metabolism. In summary, the detection of acetone in exhaled breath is a useful and promising tool for diagnosis and it can be used as a marker to follow the effectiveness of treatments in some disorders. However, further endeavors are needed for clarification of the exact distribution of acetone in different body compartments and evaluation of its complex role in humans, especially in those cases in which a ketotic state also occurs. RECEIVED

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Section: Inherited Diseases In Which Ketosis Occursmentioning

confidence: 89%

Section: Inherited Diseases In Which Ketosis Occursmentioning

confidence: 99%

Section: Inherited Diseases In Which Ketosis Occursmentioning

confidence: 99%

See 1 more Smart Citation

Breath acetone as a potential marker in clinical practice

Ruzsányi

Kalapos²

2017

J. Breath Res.

121

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“… 6 There are approximately 29 known mutations reported of the OXCT1 gene associated with SCOT deficiency. 10 This variant was reported by Erdol et al 7 in a Turkish infant with SCOT deficiency.…”

Section: Discussionmentioning

confidence: 75%

A case of severe acidosis in a 12-month-old: Succinyl-CoA:3-ketoacid-CoA transferase deficiency with OXCT1 gene mutations

Dhammi

Essakow

Gallagher

et al. 2022

SAGE Open Medical Case Reports

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Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency is a rare autosomal recessive disorder that results in severe ketoacidosis due to a defect in ketone utilization. We describe a case of a 12-month-old infant presenting with severe metabolic acidosis, ketosis, and hyperammonemia, a combination of symptoms suggestive of an inborn error of metabolism. Genetic testing found our patient had a homozygous variant in the OXCT1 gene, c.1543A>G (p.Met515Val). This was the first identified case of SCOT deficiency at our institution. We share our acute management strategies for initial stabilization in the intensive care unit, as well as our approach to preventing morning ketosis after discharge using uncooked cornstarch.

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“…Germline OXCT1-knockout (KO) mice, which lack the ability to oxidize ketone bodies in any tissue, exhibit lethality within 48 h of birth due to hyperketonemic hypoglycemia ( 13 ). Patients with OXCT1 deficiency, caused by mutations in the OXCT1 gene, present with episode of ketoacidosis (build-up of ketone bodies in the body) ( 14–16 ). In the current study, we have identified a biochemical interaction of frataxin with OXCT1 in cells including neurons.…”

Section: Introductionmentioning

confidence: 99%

Frataxin controls ketone body metabolism through regulation of OXCT1

Dong

Mesaros

et al. 2022

PNAS Nexus

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Friedreich's ataxia (FRDA) is an autosome recessive neurodegenerative disease caused by the deficiency of mitochondrial protein frataxin which plays a crucial role in iron-sulphur cluster formation and ATP production. The cellular function of frataxin is not entirely known. Here, we demonstrate that frataxin controls ketone body metabolism through regulation of 3-Oxoacid CoA-Transferase 1 (OXCT1), a rate limiting enzyme catalyzing the conversion of ketone bodies to aceto-acetyl-CoA that is then fed into the Krebs cycle. Biochemical studies show a physical interaction between frataxin and OXCT1 both in vivo and in vitro. Frataxin overexpression also increases OXCT1 protein levels in human skin fibroblasts while frataxin deficiency decreases OXCT1 in multiple cell types including cerebellum and skeletal muscle both acutely and chronically, suggesting that frataxin directly regulates OXCT1. This regulation is mediated by frataxin-dependent suppression of ubiquitin-proteasome system-dependent OXCT1 degradation. Concomitantly, plasma ketone bodies are significantly elevated in frataxin deficient knock-in/knockout (KIKO) mice with no change in the levels of other enzymes involved in ketone body production. In addition, ketone bodies fail to be metabolized to acetyl-CoA accompanied by increased succinyl-CoA in vitro in frataxin deficient cells, suggesting that ketone body elevation is caused by frataxin-dependent reduction of OXCT1 leading to deficits in tissue utilization of ketone bodies. Considering the potential role of metabolic abnormalities and deficiency of ATP production in FRDA, our results suggest a new role for frataxin in ketone body metabolism and also suggest modulation of OXCT1 may be a potential therapeutic approach for FRDA.

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A Turkish Patient With Succinyl-CoA:3-Oxoacid CoA Transferase Deficiency Mimicking Diabetic Ketoacidosis

Cited by 7 publications

References 19 publications

Breath acetone as a potential marker in clinical practice

Breath acetone as a potential marker in clinical practice

A case of severe acidosis in a 12-month-old: Succinyl-CoA:3-ketoacid-CoA transferase deficiency with OXCT1 gene mutations

Frataxin controls ketone body metabolism through regulation of OXCT1

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