scholarly journals MON-068 The First Case in Korea, ZC4H2 Gene Mutation in Wieacker-Wolff Syndrome with Recurrent Hypoglycemia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Gahyun Lee ◽  
Sejin Kim ◽  
Seokjin Kang ◽  
Heungsik Kim
Keyword(s):  
Mental Retardation ◽  
Fatty Acid ◽  
Muscular Atrophy ◽  
Serum Levels ◽  
Glycogen Storage ◽  
Acid Oxidation ◽  
First Case ◽  
Urine Organic Acid ◽  
Acid Test ◽  
Recurrent Hypoglycemia

Abstract Wieacker-Wolff syndrome was first described in 1985 and is a rare congenital syndrome cause by ZC4H2 mutation. It is a X-linked recessive disorder characterized by congenital contracture of the feet, mental retardation, progressive neurologic muscular atrophy, scoliosis, and hypoglycemia. 9-years-old boy with brain atrophy, mental retardation, scoliosis, convulsion and exotropia visited our clinic with recurrent hypoglycemia. Hypoglycemia was developed since infant. Physical examination showed dysmorphism and no hepatomegaly. In the ‘critical sample’, ketoacidosis was present and serum levels of free fatty acid was elevated. Lactate was in the normal range. Hyperinsulinism was excluded with ‘critical sample’ and glucagon stimulation test. Combined pituitary stimulation showed no deficiency of growth hormone and cortisol, respectively. Fatty acid oxidation was excluded by serum levels of acylcarnitines and urine organic acid test. Due to the presence of multiple anomaly and under the suspicion of glycogen storage type 0, whole exome sequencing was performed and p.P154T mutation on the ZC4H2 was observed. Although Sanger sequencing is in processing yet, clinical features are very similar compare to previous cases. In summary, we reported a first Korean male with a novel ZC4H2 mutation, P154T.

scholarly journals Rev-erbα heterozygosity produces a dose-dependent phenotypic advantage in mice

2019 ◽  
Author(s):  
Ryan D. Welch ◽  
Cyrielle Billon ◽  
Thomas P. Burris ◽  
Colin A. Flaveny
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Knockout Mice ◽  
Muscular Atrophy ◽  
Whole Body ◽  
Acid Oxidation ◽  
Light Cycle ◽  
Clock Proteins ◽  
Circadian Clock Proteins ◽  
Muscle Homeostasis

AbstractNumerous mutational studies have demonstrated that circadian clock proteins regulate behavior and metabolism. Nr1d1(Rev-erbα) is a key regulator of circadian gene expression and a pleiotropic regulator of skeletal muscle homeostasis and lipid metabolism. Loss of Rev-erbα expression induces muscular atrophy, high adiposity, and metabolic syndrome in mice. Here we show that, unlike knockout mice, Nr1d1 heterozygous mice are not susceptible to muscular atrophy and in fact paradoxically possess larger myofiber diameters and improved neuromuscular function, compared to wildtype mice. Heterozygous mice lacked dyslipidemia, a characteristic of Nr1d1 knockout mice and displayed increased whole-body fatty-acid oxidation during periods of inactivity (light cycle). Heterozygous mice also exhibited higher rates of glucose uptake when fasted, and had elevated basal rates of gluconeogenesis compared to wildtype and knockout littermates. Rev-erbα ablation suppressed glycolysis and fatty acid-oxidation in white-adipose tissue (WAT), whereas partial Rev-erbα loss, curiously stimulated these processes. Our investigations revealed that Rev-erbα dose-dependently regulates glucose metabolism and fatty acid oxidation in WAT and muscle.

scholarly journals Bezafibrate induces autophagy and improves hepatic lipid metabolism in glycogen storage disease type Ia

2018 ◽  
Vol 28 (1) ◽  
pp. 143-154 ◽  
Author(s):  
Lauren R Waskowicz ◽  
Jin Zhou ◽  
Dustin J Landau ◽  
Elizabeth D Brooks ◽  
Andrea Lim ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Acid Oxidation ◽  
Hepatic Glycogen ◽  
Type Ia

Abstract Glucose-6-phosphatase α (G6Pase) deficiency, also known as von Gierke’s Disease or Glycogen storage disease type Ia (GSD Ia), is characterized by decreased ability of the liver to convert glucose-6-phosphate to glucose leading to glycogen accumulation and hepatosteatosis. Long-term complications of GSD Ia include hepatic adenomas and carcinomas, in association with the suppression of autophagy in the liver. The G6pc−/− mouse and canine models for GSD Ia were treated with the pan-peroxisomal proliferator-activated receptor agonist, bezafibrate, to determine the drug’s effect on liver metabolism and function. Hepatic glycogen and triglyceride concentrations were measured and western blotting was performed to investigate pathways affected by the treatment. Bezafibrate decreased liver triglyceride and glycogen concentrations and partially reversed the autophagy defect previously demonstrated in GSD Ia models. Changes in medium-chain acyl-CoA dehydrogenase expression and acylcarnintine flux suggested that fatty acid oxidation was increased and fatty acid synthase expression associated with lipogenesis was decreased in G6pc−/− mice treated with bezafibrate. In summary, bezafibrate induced autophagy in the liver while increasing fatty acid oxidation and decreasing lipogenesis in G6pc−/− mice. It represents a potential therapy for glycogen overload and hepatosteatosis associated with GSD Ia, with beneficial effects that have implications for non-alcoholic fatty liver disease.

Fatty acid oxidation abnormalities in childhood-onset spinal muscular atrophy: Primary or secondary defect(s)?

1995 ◽  
Vol 12 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Ingrid Tein ◽  
Avril E. Sloane ◽  
Elizabeth J. Donner ◽  
Dennis C. Lehotay ◽  
David S. Millington ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Spinal Muscular Atrophy ◽  
Fatty Acid Oxidation ◽  
Muscular Atrophy ◽  
Acid Oxidation ◽  
Childhood Onset ◽  
Secondary Defect

Fatty Acid Oxidation, Electron Transfer and Riboflavin Metabolism Defects

2016 ◽  
Author(s):  
Elaine Murphy ◽  
Yann Nadjar ◽  
Christine Vianey-Saban
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Exercise Intolerance ◽  
Acid Oxidation ◽  
Inherited Disorders ◽  
Inborn Errors ◽  
Low Fat Diet ◽  
Urine Organic Acid ◽  
Life Threatening ◽  
Testing Management

The fatty acid oxidation disorders are a group of autosomally recessively inherited disorders of energy metabolism that may present with life-threatening hypoketotic hypoglycemia, encephalopathy and hepatic dysfunction, muscle symptoms, and/or cardiomyopathy. Milder phenotypes may present in adulthood, causing exercise intolerance, episodic rhabdomyolysis, and neuropathy. Specific investigations include acylcarnitine profiling, urine organic acid analysis, fibroblast or leucocyte studies of fatty acid oxidation flux/enzyme activity, and genetic testing. Management varies depending on the condition but includes avoidance of precipitants such as fasting, fever, and intense exercise, a high-carbohydrate, low-fat diet, and supplementation with carnitine or riboflavin. Inborn errors of riboflavin transport mainly present with Brown-Vialetto-Van Laere syndrome. Some patients respond dramatically to riboflavin supplementation; therefore it has to be tried in all suspected patients.

Influence of fatty acid oxidation in lateral hypothalamus on food intake and body composition

1991 ◽  
Vol 261 (2) ◽  
pp. R339-R343 ◽  
Author(s):  
J. L. Beverly ◽  
R. J. Martin
Keyword(s):  
Body Composition ◽  
Fatty Acid ◽  
Food Intake ◽  
Fatty Acid Oxidation ◽  
Serum Levels ◽  
Ventromedial Hypothalamus ◽  
Acid Oxidation ◽  
Oxidation Rates ◽  
Energy Stores ◽  
Peripheral Metabolism

This study tested the concept that the level of fatty acid oxidation in the ventrolateral hypothalamus (VLH) reflects peripheral energy stores and elicits compensatory responses to changes in energy balance status. Fatty acid oxidation rates in the VLH were chronically altered over a 14-day period by infusing into the VLH either 0.1 mM 4-pentenoic acid (4-PA; 5 ng/h) or 1.0 mM L-carnitine (L-Carn; 98 ng/h). Fatty acid oxidation rates in the VLH were altered to a similar extent as by overfeeding (reduced 37% by 4-PA) and dietary restriction (increased 28% by L-Carn). Diffusion of infusates was limited, since there were normal rates of fatty acid oxidation in the ventromedial hypothalamus and cortex. There were no significant effects of altering fatty acid oxidation in the VLH on food intake, body weight, body composition, or serum levels of glucose, insulin, and free fatty acids. The results of this experiment indicate that the level of fatty acid oxidation in the VLH is unlikely to independently elicit changes in food intake or peripheral metabolism.

scholarly journals Effect of Ezetimibe on Glucose Metabolism and Inflammatory Markers in Adipose Tissue

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 512
Author(s):  
Yongin Cho ◽  
Ryeong-Hyeon Kim ◽  
Hyunki Park ◽  
Hye Jin Wang ◽  
Hyangkyu Lee ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Glucose Metabolism ◽  
Combination Therapy ◽  
Inflammatory Cytokines ◽  
Inflammatory Markers ◽  
Serum Levels ◽  
Control Group ◽  
Acid Oxidation

Despite numerous studies, the effects of ezetimibe on glucose metabolism are poorly understood. Here, we aimed to investigate the effects of ezetimibe on glucose metabolism and the expression of inflammatory markers. Thirteen rats were randomly assigned to an ezetimibe (n = 6) or control group (n = 7). The control group received a high fat diet (HFD; 60 Kcal%), whereas the ezetimibe group received an HFD (60 Kcal%) containing 160 mg/kg of ezetimibe. After 14 weeks, adipose and liver tissues, along with plasma, were collected and comparatively analyzed. The effects of combination therapy with ezetimibe and statins on glucose metabolism were investigated over a 1-year period using data from patients with hyperlipidemia. Several indices of glucose metabolism partially improved in the ezetimibe group. The sizes of adipocytes and the accumulation of pro-inflammatory cytokines were reduced in the ezetimibe group. Ezetimibe treatment induced anti-inflammatory cytokines and fatty acid oxidation in adipocytes and reduced serum levels of free fatty acids. Clinical data analysis revealed that statin monotherapy significantly increased insulin resistance. However, combination therapy with ezetimibe and statins did not increase insulin resistance. In conclusion, ezetimibe was found to reduce the sizes of adipocytes in visceral fat and serum levels of free fatty acids, to induce fatty acid oxidation, to improve adipocytic inflammation, and to partially improve glycemic index values.

A generic emergency protocol for patients with inborn errors of metabolism causing fasting intolerance: a retrospective, single-center chart review of 128 patients

2020 ◽  
Author(s):  
Irene J. Hoogeveen ◽  
Tessa van Amerongen ◽  
Frouke J. Weynschenk ◽  
Charlotte M. A. Lubout ◽  
Foekje de Boer ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glycogen Storage Disease ◽  
Inborn Errors Of Metabolism ◽  
Storage Disease ◽  
Glycogen Storage ◽  
Acid Oxidation ◽  
Hepatic Glycogen ◽  
Inborn Errors ◽  
Fatty Acid Oxidation Defect

Abstract Background - Patients with inborn errors of metabolism causing fasting intolerance are at risk of acute metabolic decompensations. Disease specific emergency protocols are widely available, but long-term data on safety and efficacy outcomes are lacking. We hypothesized that a generic emergency protocol can be safe and effective in patients with inborn errors of metabolism causing fasting intolerance. Results - We retrospectively evaluated our generic emergency protocol in 128 patients with a hepatic glycogen storage disease or fatty acid oxidation defect between February 1, 2014 and April 24, 2019. In total, 127 hospital admissions were documented in 54 out of 128 patients (42%). Hypoglycemia (glucose concentration <3.9 mmol/l) was reported in 15% of admissions. Hypoglycemia at admission was uncommon in patients with ketotic glycogen storage disease and verbal patients with a fatty acid oxidation defect. Convulsions, coma or death were not reported. Conclusions - Generic emergency protocols can be safe and effective for home management by the caregivers and the first hour in-hospital management of metabolic emergencies in patients with hepatic glycogen storage disease and medium-chain Acyl CoA dehydrogenase deficiency.

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