Fatty Acid Oxidation Disorders Research Articles

Disease spectrum, prevalence, genetic characteristics of inborn errors of metabolism in 21,840 hospitalized infants in Chongqing, China, 2017-2022

Inborn errors of metabolism (IEMs) are uncommon. Although some studies have explored the distribution and characteristics of IEMs in newborns, the impact of these disorders on hospitalized newborns remains unclear. In this study, we gathered data from 21,840 newborn patients admitted for various medical conditions at the Children’s Hospital of Chongqing Medical University from January 2017 and December 2022. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), gas chromatography-mass spectrometry (GC-MS/MS), and genetic analysis were used to elucidate the disease spectrum, incidence rate, and genetic characteristics of IEMs in hospitalized newborns. The results revealed that the incidence of IEMs in hospitalized newborns was 1/377 (58/21,840), with a higher incidence in full-term infants (1/428) than in premature infants (1/3,120). Among the diagnosed genetic metabolic diseases, organic acid metabolism disorders (1/662), amino acid metabolism disorders (1/950), and fatty acid oxidation disorders (1/10,920) were the most prevalent. Methylmalonic acidemia (MMA), especially the isolated form, emerged as the most common IEM, while neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and ornithine transcarbamylase deficiency (OTCD) were prevalent in premature infants. Of the 58 confirmed cases of IEMs, 72 variants were identified, of which 31.94% (23/72) had not been reported previously. This study contributes to understanding the incidence and clinical features of IEMs in hospitalized newborns, offering more efficient strategies for screening and diagnosing these disorders.

Fatty acids metabolism in ozone-induced pulmonary inflammatory injury: Evidence, mechanism and prevention

Ozone (O3) is a major air pollutant that directly threatens the respiratory system, lung fatty acid metabolism disorder is an important molecular event in pulmonary inflammatory diseases. Liver kinase B1 (LKB1) and nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome not only regulate inflammation, but also have close relationship with fatty acid metabolism. However, the role and mechanism of LKB1 and NLRP3 inflammasome in lung fatty acid metabolism, which may contribute to ozone-induced lung inflammation, remain unclear, and effective strategy for preventing O3-induced pulmonary inflammatory injury is lacking. To explore these, mice were exposed to 1.00 ppm O3 (3 h/d, 5 days), and pulmonary inflammation was determined by airway hyperresponsiveness, histopathological examination, total cells and cytokines in bronchoalveolar lavage fluid (BALF). Targeted fatty acids metabolomics was used to detect medium and long fatty acid in lung tissue. Then, using LKB1-overexpressing adenovirus and NLRP3 knockout (NLRP3−/−) mice to explore the mechanism of O3-induced lung fatty acid metabolism disorder. Results demonstrated that O3 exposure caused pulmonary inflammatory injury and lung medium and long chain fatty acids metabolism disorder, especially decreased dihomo-γ-linolenic acid (DGLA). Meanwhile, LKB1 expression was decreased, and NLRP3 inflammasome was activated in lung of mice after O3 exposure. Additionally, LKB1 overexpression alleviated O3-induced lung inflammation and inhibited the activation of NLRP3 inflammasome. And we found that pulmonary fatty acid metabolism disorder was ameliorated of NLRP3 −/− mice compared with those in wide type mice after O3 exposure. Furthermore, administrating DGLA intratracheally prior to O3 exposure significantly attenuated O3-induced pulmonary inflammatory injury. Taken together, these findings suggest that fatty acids metabolism disorder is involved in O3-induced pulmonary inflammation, which is regulated by LKB1-mediated NLRP3 pathway, DGLA supplement could be a useful preventive strategy to ameliorate ozone-associated lung inflammatory injury.

A new mutation of the ETFDH gene is responsible for the mitochondrial fatty-acid oxida-tion disorder in adults

A new mutation of the ETFDH gene is responsible for the mitochondrial fatty-acid oxida-tion disorder in adults

What is the impact of long-chain fatty acid oxidation disorders on everyday life? Plain language summary of a survey

What is this summary about? Long-chain fatty acid oxidation disorders (LC-FAOD for short) are a group of rare conditions where the body cannot use stored fat for energy. This leads to symptoms and health problems that can be life-threatening, but the impact of LC-FAOD on the everyday life of people with LC-FAOD and their caregivers has not been well studied. What was done? We conducted a burden of illness survey in the United States of people with LC-FAOD and their caregivers to help show the impact of this condition on their everyday life. The survey had 44 people who completed the survey (respondents): 14 adults (≥18 years) living with LC-FAOD and 30 caregivers reporting on 37 people with LC-FAOD. People with LC-FAOD reported on in the survey were 8 months to 67 years old (the average age was 16 years). What were the results? We found that the LC-FAOD symptoms impact people differently through the stages of life. People with LC-FAOD and their caregivers reported an impact on school and work, including missing work; the main reasons were hospitalizations (staying in the hospital as an inpatient) and physical symptoms. In addition, many people had trouble performing everyday activities, such as standing for 2 hours, walking a quarter of a mile, moving heavy objects, and doing household chores. Using a standard questionnaire, we found that the overall quality of life of people with LC-FAOD was lower than for the average American who does not have LC-FAOD. What do the results mean? The findings from the survey help show how LC-FAOD can impact the everyday life of people living with LC-FAOD and their caregivers. The findings provide people with LC-FAOD a better understanding of their condition and what they might expect. The findings also help researchers and healthcare providers support people with an LC-FAOD and their caregivers.

Newborn screening in France: news and perspectives

Newborn screening is a major public health concern. In France, it was established in 1972 with systematic screening for phenylketonuria. Subsequently, other screenings, including congenital hypothyroidism, congenital adrenal hyperplasia, cystic fibrosis, and sickle cell disease, were added. The introduction of tandem mass spectrometry in screening laboratories in 2020 enabled the inclusion of eight additional inherited metabolic diseases: aminoacidopathies (tyrosinemia type I, maple syrup urine disease, and homocystinuria), organic acidurias (isovaleric and glutaric type I acidurias), and disorders of fatty acid metabolism (MCADD, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), and primary carnitine deficiency). We briefly present these newly added diseases, of which public awareness is still incomplete.

Early diagnosis and treatment by newborn screening (NBS) or family history is associated with improved visual outcomes for long-chain 3-hydroxyacylCoA dehydrogenase deficiency (LCHADD) chorioretinopathy.

Long chain 3-hydroxyacyl-CoA dehydrogenase (LCHADD) is the only fatty acid oxidation disorder to develop a progressive chorioretinopathy resulting in vision loss; newborn screening (NBS) for this disorder began in the United States around 2004. We compared visual outcomes among 40 participants with LCHADD or trifunctional protein deficiency diagnosed symptomatically to those who were diagnosed via NBS or a family history. Participants completed ophthalmologic testing including measures of visual acuity, electroretinograms (ERG), fundal imaging, contrast sensitivity, and visual fields. Records were reviewed to document medical and treatment history. Twelve participants presented symptomatically with hypoglycemia, failure to thrive, liver dysfunction, cardiac arrest, or rhabdomyolysis. Twenty eight were diagnosed by NBS or due to a family history of LCHADD. Participants diagnosed symptomatically were older but had similar percent males and genotypes as those diagnosed by NBS. Treatment consisted of fasting avoidance, dietary long-chain fat restriction, MCT, C7, and/or carnitine supplementation. Visual acuity, rod- and cone-driven amplitudes on ERG, contrast sensitivity scores, and visual fields were all significantly worse among participants diagnosed symptomatically compared to NBS. In mixed-effects models, both age and presentation (symptomatic vs. NBS) were significant independent factors associated with visual outcomes. This suggests that visual outcomes were improved by NBS, but there was still lower visual function with advancing age in both groups. Early diagnosis and treatment by NBS is associated with improved visual outcomes and retinal function compared to participants who presented symptomatically. Despite the impact of early intervention, chorioretinopathy was greater with advancing age, highlighting the need for novel treatments.

Hovenia dulcis Fruit Peduncle Polysaccharides Reduce Intestinal Dysbiosis and Hepatic Fatty Acid Metabolism Disorders in Alcohol-Exposed Mice.

Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) have the potential to alleviate alcoholic liver injury and play essential roles in treating alcohol-exposed liver disease; however, the hepatoprotective effects and mechanisms remain elusive. In this study, we investigated the hepatoprotective effects of HDPs and their potential mechanisms in alcohol-exposed mice through liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels, and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. When applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria, significant increases in Firmicutes at the phylum level, increased Lactobacillus abundance, and decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid and glycerophospholipid metabolism, and identified two important metabolites-C00157 (phosphatidylcholine, a glycerophospholipid plays a central role in energy production) and C04230 (1-Acyl-sn-glycero-3-phosphocholine, a lysophospholipid involved in the breakdown of phospholipids)-involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs have a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.

Comparative analysis of inherited metabolic diseases in normal newborns and high-risk children: Insights from a 10-year study in Shanghai

BackgroundCompare the differences between normal newborns and high-risk children with inherited metabolic diseases. The disease profile includes amino acidemias, fatty acid oxidation disorders, and organic acidemias. MethodsData was collected on newborns and children from high-risk populations in Shanghai from December 2010 to December 2020. Results232,561 newborns were screened for disorders of organic, amino acid, and fatty acid metabolism. The initial positive rate was 0.66 % (1,526/232,561) and the positive recall rate was 77.85 %. The positive predictive value is 4.71 %. Among them, 56 cases were diagnosed as metabolic abnormalities. The total incidence rate is 1:4153. Hyperphenylalaninemia and short-chain acyl-CoA dehydrogenase are the most common diseases in newborns. In addition, in 56 children, 39 (69.42 %) were diagnosed by genetic sequencing. Some hotspot mutations in 14 IEMs have been observed, including PAH gene c.728G > A, c.611A > G, and ACADS gene c. 1031A > G, c.164C > T. A total of 49,860 symptomatic patients were screened, of which 185 were diagnosed with IEM, with a detection rate of 0.37 %. The most commonly diagnosed diseases in high-risk infants aremethylmalonic acidemia and hyperphenylalaninemia. ConclusionThere are more clinical cases of congenital metabolic errors diagnosed by tandem mass spectrometry than newborn screening. The spectrum of diseases, prevalence, and genetic characteristics of normal newborns and high-risk children are quite different.

Early results from a long-term disease monitoring program in patients with long-chain fatty acid oxidation disorders

Early results from a long-term disease monitoring program in patients with long-chain fatty acid oxidation disorders

Revealing the genetic complexity of long-chain fatty acid oxidation disorders: Insights from a dynamic locus-specific gene database

Revealing the genetic complexity of long-chain fatty acid oxidation disorders: Insights from a dynamic locus-specific gene database

Long-chain Fatty Acid Oxidation Disorders, Early Diagnosis and Role of Breastfeeding

ZusammenfassungEin männliches Neugeborenes, zweites Kind nichtkonsanguiner Eltern, wurde termingerecht per Kaiserschnitt mit 38 + 6 Schwangerschaftswochen und einem Geburtsgewicht von 3340 g geboren. Bereits am 4. Lebenstag zeigten sich auffallende Symptome, darunter rezidivierendes Erbrechen, Hypoglykämie-Episoden und eine Gewichtsabnahme von über 10 %. Das Kind wurde zur weiteren Abklärung an ein medizinisches Zentrum mit Neugeborenen-Intensivstation transferiert. Das Neugeborenen-Screening (NGS) traf am 5. Lebenstag ein und wies auf eine langkettige Fettsäureoxidationsstörung hin (LC-FAOD). Eine umfassende Stoffwechselabklärung und genetische Diagnostik wurden eingeleitet, welches die Diagnose LCHAD-Defizienz im Verlauf bestätigte. Während des stationären Aufenthalts wurde der Fokus auf regelmäßige Stillmahlzeiten gelegt, um katabolen Phasen vorzubeugen. Der Säugling wurde am 12. Lebenstag auf die Normalstation verlegt und am 14. Lebenstag entlassen. Die multidisziplinäre Betreuung, regelmäßige ärztliche Überwachung und eine angepasste Ernährung spielten eine entscheidende Rolle im erfolgreichen Management der seltenen angeborenen Stoffwechselstörung. Das NGS hat eine wesentliche Bedeutung bei der frühzeitigen Erkennung gut beherrschbarer angeborener Stoffwechselstörungen. LC-FAODs beeinträchtigen den Abbau von Fettsäuren und können zu schweren gesundheitlichen Problemen führen. Die Symptome variieren, erfordern jedoch eine enge Zusammenarbeit verschiedener medizinischer Fachkräfte. Stillen bei Neugeborenen gilt als adäquate, altersentsprechende Ernährung, da es – auch für Kinder mit metabolischen Erkrankungen – zahlreiche gesundheitliche Vorteile für Kind und Mutter bietet und auch die Bindung zwischen Mutter und Kind fördert. Die einzigartige Zusammensetzung der Muttermilch passt sich den Bedürfnissen des Kindes an. Der geschilderte Fall betont die Bedeutung des NGS, die Zusammenarbeit verschiedener Fachbereiche sowie die Rolle von Stillen, Triheptanoin-Supplementierung im Verlauf und angepasster Ernährung im Umgang mit langkettigen Fettsäureoxidationsstörungen. Frühe Diagnose und ein umfassender Ansatz sind entscheidend für die bestmögliche Betreuung und Lebensqualität.

Gut microbiota-palmitoleic acid-interleukin-5 axis orchestrates benzene-induced hematopoietic toxicity

ABSTRACT Due to the annual increase in its production and consumption in occupational environments, the adverse blood outcomes caused by benzene are of concern. However, the mechanism of benzene-induced hematopoietic damage remains elusive. Here, we report that benzene exposure causes hematopoietic damage in a dose-dependent manner and is associated with disturbances in gut microbiota-long chain fatty acids (LCFAs)-inflammation axis. C57BL/6J mice exposed to benzene for 45 days were found to have a significant reduction in whole blood cells and the suppression of hematopoiesis, an increase in Bacteroides acidifaciens and a decrease in Lactobacillus murinus. Recipient mice transplanted with fecal microbiota from benzene-exposed mice showed potential for hematopoietic disruption, LCFAs, and interleukin-5 (IL-5) elevation. Abnormally elevated plasma LCFAs, especially palmitoleic acid (POA) exacerbated benzene-induced immune-inflammation and hematopoietic damage via carnitine palmitoyltransferase 2 (CPT2)-mediated disorder of fatty acid oxidation. Notably, oral administration of probiotics protects the mice against benzene-induced hematopoietic toxicity. In summary, our data reveal that the gut microbiota-POA-IL-5 axis is engaged in benzene-induced hematopoietic damage. Probiotics might be a promising candidate to prevent hematopoietic abnormalities from benzene exposure.

Clinicobiochemical Profile and Outcome of Children with Small Molecule Neurometabolic Disorders: A Tertiary Care Hospital Experience from India

AbstractInborn Errors of Metabolism (IEM), though heterogenous, are not uncommon. Neurologic manifestations predominate. Without universal newborn screening, early diagnosis and treatment may lessen neuromorbidity. Hence, this study was done to understand small molecule neurometabolic disorders' presentation, diagnostic clues, and outcome.Small molecule neurometabolic disorder was diagnosed in 45 children (postneonatal onset) over 14 years (2008–2022) in a tertiary care hospital. Clinical and laboratory data were retrospectively analyzed.There were 26 boys and 19 girls. The median age at diagnosis was 19 months (interquartile range [IQR] 8–38 months). The median diagnostic delay was 12 months in chronic encephalopathy (IQR 1–24 months) and 1 month (IQR 0.2–5.5 months) in the acute encephalopathy group (p ≤ 0.01). The presentation mode was chronic encephalopathy/myopathy in 29 (64.4%) and acute encephalopathy in 11 (24.4%). Diagnostic clues included unexplained developmental delay (n = 27, 60%), tone abnormalities (n = 26, 57.7%), movement disorder and ataxia (n = 16, 35.5%), acute encephalopathy (n = 11, 24.4%), neuroregression (n = 10, 22.2%), macrocephaly (n = 10, 22.2%), and alopecia (n = 4, 8.9%). Diagnostic/suggestive blood-spot tandem mass spectrometry (TMS) was seen in 34/38 (89.5%) children. Neuroimaging helped clinch the diagnosis in 17 (47%) children. Diagnostic categories were organic acidemias (n = 25, 55.6%), urea cycle disorders (n = 11, 24.4%), aminoacidopathies (n = 5, 11.1%), and fatty acid oxidation disorders (n = 4, 8.9%). The neurodevelopmental outcome was normal in 13 (28.8%), mild delay in 12 (26.6%), severe delay in 11 (24.4%), 3 deaths (6.6%), and 6 (13.3%) children being lost to follow-up. Overall, the outcome was favorable in 55% of cases.Unexplained developmental delay with tone abnormalities with or without movement disorders is a joint presentation of late-onset neurometabolic diseases. Neuroimaging studies and laboratory tests like blood-spot TMS help identify many small molecule disorders.

Major clinical events and healthcare resource use among patients with long-chain fatty acid oxidation disorders in the United States: Results from LC-FAOD Odyssey program

Major clinical events (MCEs) related to long-chain fatty acid oxidation disorders (LC-FAOD) in triheptanoin clinical trials include inpatient or emergency room (ER) visits for three major clinical manifestations: rhabdomyolysis, hypoglycemia, and cardiomyopathy. However, outcomes data outside of LC-FAOD clinical trials are limited. The non-interventional cohort LC-FAOD Odyssey study examines data derived from US medical records and patient reported outcomes to quantify LC-FAOD burden according to management strategy including MCE frequency and healthcare resource utilization (HRU).Thirty-four patients were analyzed of which 21 and 29 patients had received triheptanoin and/or medium chain triglycerides (MCT), respectively. 36% experienced MCEs while receiving triheptanoin versus 54% on MCT. Total mean annualized MCE rates on triheptanoin and MCT were 0.1 and 0.7, respectively. Annualized disease-related inpatient and ER events were lower on triheptanoin (0.2, 0.3, respectively) than MCT (1.2, 1.0, respectively). Patients were managed more in an outpatient setting on triheptanoin (8.9 annualized outpatient visits) vs MCT (7.9). Overall, this shows that those with LC-FAOD in the Odyssey program experienced fewer MCEs and less HRU in inpatient and ER settings during triheptanoin-treated periods compared with the MCT-treated periods. The MCE rate was lower after initiation of triheptanoin, consistent with clinical trials.

Using the C14:1/Medium-Chain Acylcarnitine Ratio Instead of C14:1 to Reduce False-Positive Results for Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency in Newborn Screening in Japan.

Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a long-chain fatty acid oxidation disorder that manifests as either a severe phenotype associated with cardiomyopathy, a hypoglycemic phenotype, or a myopathic phenotype. As the hypoglycemic phenotype can cause sudden infant death, VLCAD deficiency is included in newborn screening (NBS) panels in many countries. The tetradecenoylcarnitine (C14:1) level in dried blood specimens is commonly used as a primary marker for VLCAD deficiency in NBS panels. Its ratio to acetylcarnitine (C2) and various other acylcarnitines is used as secondary markers. In Japan, tandem mass spectrometry-based NBS, initially launched as a pilot study in 1997, was introduced to the nationwide NBS program in 2013. In the present study, we evaluated levels of acylcarnitine with various chain lengths (C18 to C2), free carnitine, and their ratios in 175 infants who tested positive for VLCAD deficiency with C14:1 and C14:1/C2 ratios. Our analyses indicated that the ratios of C14:1 to medium-chain acylcarnitines (C10, C8, and C6) were the most effective markers in reducing false-positive rates. Their use with appropriate cutoffs is expected to improve NBS performance for VLCAD deficiency.

Impact of newborn screening for fatty acid oxidation disorders on neurological outcome: A Belgian retrospective and multicentric study

Fatty acid oxidation (FAO) disorders are autosomal recessive genetic disorders affecting either the transport or the oxidation of fatty acids. Acute symptoms arise during prolonged fasting, intercurrent infections, or intense physical activity. Metabolic crises are characterized by alteration of consciousness, hypoglycemic coma, hepatomegaly, cardiomegaly, arrhythmias, rhabdomyolysis, and can lead to death. In this retrospective and multicentric study, the data of 54 patients with FAO disorders were collected. Overall, 35 patients (64.8%) were diagnosed after newborn screening (NBS), 17 patients on clinical presentation (31.5%), and two patients after family screening (3.7%). Deficiencies identified included medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (75.9%), very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (11.1%), long-chain hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency (3.7%), mitochondrial trifunctional protein (MTP) deficiency (1.8%), and carnitine palmitoyltransferase 2 (CPT 2) deficiency (7.4%). The NBS results of 25 patients were reviewed and the neurological outcome of this population was compared with that of the patients who were diagnosed on clinical presentation. This article sought to provide a comprehensive overview of how NBS implementation in Southern Belgium has dramatically improved the neurological outcome of patients with FAO disorders by preventing metabolic crises and death. Further investigations are needed to better understand the physiopathology of long-term complications in order to improve the quality of life of patients and to ensure optimal management.

Prevalence of inherited metabolic disorders among newborns in Zhuzhou, a southern city in China.

Background and aims: Defective enzymes, cofactors, or transporters of metabolic pathways cause inherited metabolic disorders (IMDs), a group of genetic disorders. Several IMDs have serious consequences for the affected neonates. Newborn screening for IMDs is conducted by measuring specific metabolites between 3 and 7days of life. Herein, we analyzed the incidence, spectrum, and genetic characteristics of IMDs in newborns in the Zhuzhou area. Methods: Tandem mass spectrometry was conducted on 90,829 newborns who were admitted to the Women and Children Healthcare Hospital of Zhuzhou and requested for screening for IMDs. These newborns were subsequently subjected to next-generation sequencing and further validated using Sanger sequencing. Results: 30 IMDs cases were found in 90,829 cases of newborns screened for IMDs, and the overall incidence was 1/3,027. The incidence of amino acid, organic acid, fatty acid oxidation and urea cycle disorders were 1/8,257, 1/18,165, 1/7,569, and 1/45,414, respectively. Additionally, 9 cases of maternal IMDs were found in our study, and unreported gene mutations of 3 cases IMDs were identified. Conclusion: Our data indicated that IMDs are never uncommon in zhuzhou, meanwhile, we also found that primary carnitine deficiency was the only disorder of fatty acid oxidation in Zhuzhou, and the incidence (1/7,569) was higher than the national level, organic acid metabolic diseases are mostly inherited. Therefore, our study has clarified the disease spectrum and genetic backgrounds, contributing to the treatment and prenatal genetic counseling of these disorders in this region.

Glycolytic enzymes in non-glycolytic web: functional analysis of the key players.

To survive in the tumour microenvironment, cancer cells undergo rapid metabolic reprograming and adaptability. One of the key characteristics of cancer is increased glycolytic selectivity and decreased oxidative phosphorylation (OXPHOS). Apart from ATP synthesis, glycolysis is also responsible for NADH regeneration and macromolecular biosynthesis, such as amino acid biosynthesis and nucleotide biosynthesis. This allows cancer cells to survive and proliferate even in low-nutrient and oxygen conditions, making glycolytic enzymes a promising target for various anti-cancer agents. Oncogenic activation is also caused by the uncontrolled production and activity of glycolytic enzymes. Nevertheless, in addition to conventional glycolytic processes, some glycolytic enzymes are involved in non-canonical functions such as transcriptional regulation, autophagy, epigenetic changes, inflammation, various signaling cascades, redox regulation, oxidative stress, obesity and fatty acid metabolism, diabetes and neurodegenerative disorders, and hypoxia. The mechanisms underlying the non-canonical glycolytic enzyme activities are still not comprehensive. This review summarizes the current findings on the mechanisms fundamental to the non-glycolytic actions of glycolytic enzymes and their intermediates in maintaining the tumor microenvironment.

Pediatric Cardiomyopathies from the Landscape of Inherited Metabolic Disorders in Southeastern Turkey

Background: Cardiomyopathy (CM) is an important factor affecting inherited metabolic disorders (IMDs). Therefore, documentation of real-world data can increase awareness, and early diagnosis and treatment may improve the outcome. Objectives: The aim of this study was to delineate the underlying etiologies and clinical findings of patients with CM due to IMDs. Methods: In this single-center retrospective study, we aimed to examine the demographic, clinical, and echocardiographic data and prognosis of patients aged 0 - 18 who were diagnosed with CM associated with IMDs between 2010 and 2020. Results: A total of 102 patients were included in the study. Families with consanguineous parents constituted 84.3% of the study population. The mean age of the patients at the time of diagnosis of CM was 26.2 ± 28.2 months. Eighty-six (84.3%) of the patients were diagnosed with hypertrophic CM (HCM), 12 (11.7%) with dilated CM (DCM), and 4 (3.9%) with mixt-type CM. Of the patients, 60 (58.8%) had glycogen storage disease (GSD), 17 (16.6%) had lysosomal storage disorders (LSDs), 11 (10.7%) had fatty acid oxidation disorders, 11 (10.7%) had mitochondrial disorders, and 3 (2.9%) had amino acid and organic acid metabolism disorders. Arrhythmia was detected in 24 patients (23.5%). Fifty-six patients received enzyme replacement therapy (ERT). The echocardiographic parameters of the Pompe patients improved significantly with ERT. The mean follow-up period was 60.9 ± 54.6 months. Thirty-eight (36.1%) of 95 patients with regular follow-up died. Cardiomyopathy type did not affect mortality. Conclusions: Increasingly, cardiac complications have been defined as IMDs. Evaluation should be made in terms of IMDs in unexplained CM and rhythm disorders. On the other hand, patients with certain IMDs should be regularly screened for cardiac complications.

Mitochondrial Pharmacotherapeutics - Advancements and Applications

Mitochondria, known as the “powerhouse of the cell”, plays an important role in the occurrence of multiple diseases and disorders. Mitochondria are believed to come into existence from the synergistic relationship between the proto-eukaryotic and primitive prokaryotic efficient by oxidative phosphorylation. It is the major hub of Adenosine Tri Phosphate production through the implementation of oxidative phosphorylation. It is the processing unit of the “Electron transport chain”. Mitochondria is useful in dealing with various cancers, cardiovascular problems, fatty-acid oxidation disorders, and several kinds of tumours and also several cancers.