Inborn Errors of Metabolism

2019 ◽  
Author(s):  
S. Joy Dean
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Pediatric Population ◽  
Treatment Strategies ◽  
Acid Oxidation ◽  
Childbearing Age ◽  
Inherited Disorders ◽  
Inborn Errors ◽  
Management Guidelines ◽  
Fatty Acid Oxidation Disorders ◽  
Lipid Metabolism Disorders

Inborn errors of metabolism are a group of inherited disorders that are generally due to a block in an enzymatic pathway. In the past, individuals with inborn errors of metabolism were mainly isolated to the pediatric population. However, with the advent of newborn screening and improved treatment strategies, these patients are now reaching childbearing age. Many successful pregnancies in females with various inborn errors of metabolism have been reported. It is pertinent that obstetrician gynecologists are aware of these conditions and their management guidelines. This review will discuss three main categories of inborn errors of metabolism including protein metabolism disorders, carbohydrate metabolism disorders, and lipid metabolism disorders. This review contains 5 tables, and 30 references. Keywords: Inborn errors of metabolism, phenylketonuria, maternal PKU syndrome, ornithine transcarbamylase deficiency, galactosemia, fatty acid oxidation disorders

scholarly journals L-Carnitine and Acylcarnitines: Mitochondrial Biomarkers for Precision Medicine

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 51
Author(s):  
Marc R. McCann ◽  
Mery Vet George De la Rosa ◽  
Gus R. Rosania ◽  
Kathleen A. Stringer
Keyword(s):  
Precision Medicine ◽  
Inborn Errors Of Metabolism ◽  
Clinical Utility ◽  
Biomarker Discovery ◽  
Genetic Disorders ◽  
Acid Oxidation ◽  
Inborn Errors ◽  
Therapeutic Decisions ◽  
Literature Evidence ◽  
Clinical Biomarker

Biomarker discovery and implementation are at the forefront of the precision medicine movement. Modern advances in the field of metabolomics afford the opportunity to readily identify new metabolite biomarkers across a wide array of disciplines. Many of the metabolites are derived from or directly reflective of mitochondrial metabolism. L-carnitine and acylcarnitines are established mitochondrial biomarkers used to screen neonates for a series of genetic disorders affecting fatty acid oxidation, known as the inborn errors of metabolism. However, L-carnitine and acylcarnitines are not routinely measured beyond this screening, despite the growing evidence that shows their clinical utility outside of these disorders. Measurements of the carnitine pool have been used to identify the disease and prognosticate mortality among disorders such as diabetes, sepsis, cancer, and heart failure, as well as identify subjects experiencing adverse drug reactions from various medications like valproic acid, clofazimine, zidovudine, cisplatin, propofol, and cyclosporine. The aim of this review is to collect and interpret the literature evidence supporting the clinical biomarker application of L-carnitine and acylcarnitines. Further study of these metabolites could ultimately provide mechanistic insights that guide therapeutic decisions and elucidate new pharmacologic targets.

A Five-Year-Old Boy with GAII Administered with High-Dose Riboflavin: A Case Report

2020 ◽  
Author(s):  
Naser Ali Mirhosseini ◽  
Sana Taghiyar ◽  
Mahdieh Saatchi ◽  
Zeynab Eshaghiyeh
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Pediatric Population ◽  
Acid Oxidation ◽  
High Dose ◽  
Inborn Errors ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Congenital Deficiency ◽  
Mitochondrial Fatty Acid

Background: Inborn errors of metabolism can cause a number of morbidities and mortality in pediatric population. Glutaric aciduria II (GAII) or multiple acyl-CoA dehydrogenase deficiency (MADD) is an ultra-rare (i.e. <1:50 000) disorder of mitochondrial fatty acid oxidation (FAO) and amino acid metabolism. It is inherited in an autosomal recessive manner. Congenital deficiency of electron transfer flavoproteins and ETF dehydrogenase genes cause an illness that combines the features of impaired fatty acid oxidation and impaired oxidation of several aminoacides. Newborn screening (NBS) using tandem mass spectrometry (MS/MS) permits detection of neonates with glutaricaciduria-Type II. Case Presentation: We reported a five-year-old boy with muscle weakness of lower limb and inability to walk (myopathy), seizure due to hypoglycemia (as a result of prolonged fasting), hepatomegaly and rhabdomyolysis that treated with high dose riboflavin and he is well in follow up. Conclusion: Early diagnosis of mild cases and treatment with high dose riboflavin may have better prognosis.

Inborn errors of metabolism diagnosed in sudden death cases by acylcarnitine analysis of postmortem bile

1995 ◽  
Vol 41 (8) ◽  
pp. 1109-1114 ◽  
Author(s):  
M S Rashed ◽  
P T Ozand ◽  
M J Bennett ◽  
J J Barnard ◽  
D R Govindaraju ◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Dehydrogenase Deficiency ◽  
Sudden Infant Death ◽  
Diagnostic Methods ◽  
First Episode ◽  
Acid Oxidation ◽  
Sudden Infant ◽  
Inborn Errors ◽  
Postmortem Diagnosis ◽  
Acylcarnitine Analysis

Abstract Fatty acid oxidation (FAO) disorders represent a frequently misdiagnosed group of inborn errors of metabolism. Some patients die at the first episode of fasting intolerance and, if appropriate investigations are not undertaken, often meet the criteria of sudden infant death syndrome (SIDS). To expand existing protocols for the postmortem diagnosis of FAO and other metabolic disorders, we tested the hypothesis that analysis for acylcarnitine in bile, a specimen readily available at autopsy, may be utilized for diagnostic purposes. Using electrospray/tandem mass spectrometry, we analyzed for acylcarnitine postmortem bile specimens from two infants with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, one infant with glutaryl-CoA dehydrogenase deficiency, and 17 uninformative SIDS cases as controls. The affected cases, and none of the controls, showed marked accumulation of C10-C18 acylcarnitines or glutarylcarnitine (acyl/free carnitine ratio: 5.2, 2.7, and 1.9, respectively; controls 0.2 +/- 0.1). In one patient, all other diagnostic methods were uninformative, suggesting that bile acylcarnitine profiling could lead to identification of previously overlooked cases.

Non-immune fetal hydrops of metabolic origin: a case report and a review of the literature

2017 ◽  
Vol 6 (2) ◽  
Author(s):  
Ana Carvoeiro ◽  
Filipa Carvalho ◽  
Nuno Montenegro ◽  
Alexandra Matias
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Diagnostic Algorithm ◽  
Primiparous Woman ◽  
Lysosomal Storage ◽  
Review Of The Literature ◽  
Fetal Hydrops ◽  
Autopsy Study ◽  
Inherited Disorders ◽  
Lysosomal Disease ◽  
Inborn Errors

Abstract Aim To propose a diagnostic algorithm for non-immune fetal hydrops (NIFH) of metabolic origin based on a review of the literature and on the workup of a clinical case. Background The etiology of NIFH is complex and remains unexplained in 15%–25% of patients. The appropriate work up beyond an initial approach is still not well defined but it should include screening for metabolic conditions. Inborn errors of metabolism comprise a heterogeneous group of autosomal recessive rare inherited disorders, among which lysosomal storage disorder is the most common subtype. Case description We report a case of a 30-year-old pregnant, primiparous woman, referred to a tertiary hospital at 22 weeks of gestation because of a fetal hydrops. The second trimester obstetric ultrasound showed a hydrothorax and a large subcutaneous edema. At 30 weeks of gestation, the fetal health status deteriorated and a massive hepatomegaly was detected. The metabolic study of the amniotic fluid supernatant suggested a lysosomal disease. The ominous prognosis of the condition motivated the parents to opt for a termination of pregnancy. The autopsy study confirmed the existence of a metabolic disease. Conclusion The incidence of inborn errors of metabolism may be significantly higher in NIHF than reported previously. Consequently, an extensive investigation for the etiology of NIHF including the screening for metabolic disorders seems to be crucial for a definitive diagnosis. Clinical relevance Despite the lack of treatment options for the majority of these disorders, it is of great importance to follow an established workup, in order to identify the index case as soon as possible, as pregnancy management decisions and prenatal counselling in future pregnancies will depend on a more precise diagnosis.

Inborn errors of metabolism in the Italian pediatric population: A national retrospective survey

2002 ◽  
Vol 140 (3) ◽  
pp. 321-329 ◽  
Author(s):  
Carlo Dionisi-Vici ◽  
Cristiano Rizzo ◽  
Alberto B. Burlina ◽  
Ubaldo Caruso ◽  
Gaetano Sabetta ◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Pediatric Population ◽  
Inborn Errors ◽  
Retrospective Survey

Inherited Metabolic Diseases (IMDs) and Pregnancy

2018 ◽  
Author(s):  
Ahmed I. Ahmed ◽  
Sarah Aldhaheri ◽  
Allison Bannick
Keyword(s):  
Metabolic Diseases ◽  
Genetic Disorders ◽  
Acid Oxidation ◽  
Childbearing Age ◽  
Inherited Disorders ◽  
Inherited Metabolic Diseases ◽  
Neurological Outcomes ◽  
Maternal Metabolism ◽  
Pregnancy And Postpartum ◽  
Cycle Disorders

Inherited metabolic diseases (IMDs) are rare genetic disorders: clinically heterogeneous, and they can present at any age. With the expanded newborn screening panels, many of the IMDs have been successfully screened. Early diagnosis and treatment of these conditions have led to improved neurological outcomes and overall survival of these individuals, and now many of them are reaching childbearing age. Despite treatment, the potential presence of preexisting organ involvement may not only impact their fertility potentials but also may impose a higher risk of adverse maternal and fetal outcomes. Pregnancy leads to an extra strain on maternal metabolism; this may result in the manifestation of symptoms of a previously unknown disease or a progression of a known disease. This chapter will address the possible complications of some inherited disorders of metabolism that are associated with maternal or fetal neurological manifestations such as disorders of energy metabolism (eg, mitochondrial disorders, adult onset urea cycle disorders, ornithine transcarbamylase (OTC) deficiency, amino acidopathies, phenylketonuria (PKU), and impaired fatty acid oxidation disorders). We will provide special emphasis on the available potential treatments and plan of care during pregnancy and postpartum periods.

Metabolic Disorders

2016 ◽  
Author(s):  
Lance Rodan
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Urea Cycle ◽  
Acid Oxidation ◽  
Catabolic Pathway ◽  
Peroxisomal Disorders ◽  
Inborn Errors ◽  
Lysosomal Disorders ◽  
Cycle Disorders ◽  
Cobalamin Disorders

Inborn errors of metabolism (IEM) are individually rare but have a collective incidence of approximately one in 1000. Most IEM can manifest with neurologic symptoms. It is crucial for the pediatric neurologist to be familiar with the evaluation and management of these disorders because many are amenable to specific treatments. This review provides a category-based approach to the diagnosis and treatment of IEM organized by metabolic pathway and organelle. Categories include disorders of mitochondrial fatty acid oxidation and carnitine metabolism, urea cycle disorders, organic acidemias, aminoacidopathies, lysosomal disorders, peroxisomal disorders, vitamin- and diet-responsive metabolic epilepsies, and neurotransmitter disorders. Multiple summary tables for quick reference are provided. Figures show mitochondrial β-oxidation and carnitine cycle; urea cycle; T2-weighted magnetic resonance images (MRI) of ornithine transcarbamylase deficiency presenting with hyperammonemic encephalopathy, propionic academia, methylmalonic academia, glutaric acidemia type 1, ethylmalonic encephalopathy, mitochondrial complex 1 deficiency, pyruvate dehydrogenase complex E3 deficiency, untreated biotin-thiamine-responsive basal ganglia disease, homocysteinemia and low plasma methionine (suspected remethylation defect), attenuated Krabbe disease, Hunter syndrome, and GM1-gangliosidosis; branched-chain amino acid catabolic pathway; lysine, hydroxylysine, and tryptophan catabolic pathway; intracellular cobalamin metabolism; metabolism of homocysteine; diffusion-weighted imaging of maple syrup urine disease, nonketotic hyperglycinemia, and poorly controlled phenylketonuria; sphingolipid metabolic pathway; skeletal surveys of Hurler syndrome demonstrating features of dysostosis multiplex and rhizomelic chondrodysplasia punctata type 1; MRI of Salla disease; peroxisomal oxidation reactions, and the biogenic amine biosynthetic pathway. Tables list fatty acid oxidation and carnitine disorders, metabolic myopathies presenting with recurrent rhabdomyolysis, urea cycle disorders, organic acidemias, IEM associated with abnormal head size, cobalamin disorders, aminoacidopathies, IEM associated with abnormal odor, lysosomal disorders, lysosomal disease Symptom categories (Not mutually exclusive), peroxisomal disorders, IEM associated with brain malformations, vitamin- and diet-responsive epilepsies, neurotransmitter disorders, and IEM associated with brain mineralization. This review contains 26 highly rendered figures, 15 tables, and 71 references. Key words: Inborn errors of metabolism, organic acidemia, cobalamin disorders, aminoacidopathy, lysosomal disorders

scholarly journals Detection of some metabolic disorders in suspected neonates admitted at Assiut University Children Hospital

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Shaimaa Mohamed Khalaf ◽  
Mohamed Mahrous El-Tellawy ◽  
Nafisa Hassan Refat ◽  
Amal Mohammed Abd El-Aal
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Metabolic Disorders ◽  
Screening Program ◽  
The Body ◽  
Acid Oxidation ◽  
High Morbidity ◽  
Inborn Errors ◽  
Phenylalanine Level ◽  
Maple Syrup ◽  
Urea Cycle Defect

Abstract Background Inborn errors of metabolism are genetically inherited diseases which can lead to accumulation of toxic metabolites in the body. Inborn errors of metabolism have a high morbidity and mortality in neonates. Many inborn errors of metabolism are amenable to treatment with early diagnoses. Till now, more than 500 metabolic disorders have been detected. Although individual metabolic disorders are rare, the incidence of overall metabolic disorders is high. Results It was found that 70/200 cases (35 %) had confirmed inborn errors of metabolism, and another 8 cases (4%) suspected to have inborn errors of metabolism; 15/200 (7.5%) cases had mild elevation of phenylalanine level, while 107/200 (53.5%) had another diagnosis rather than metabolic disorders. Urea cycle defect was diagnosed in 20/70 (28.5%), maple syrup urine disease in 18/70 (25.7%), organic acidemia in 15/70 (21.4%), and non-ketotic hyperglycinemia in 1/70 (1.4 %) case. Also, 15/70 (21.4 %) cases had fatty acid oxidation defect. Lastly, one female case (1.4 %) was diagnosed to have disorder of pyrimidine deficiency. Conclusion Diagnosis of inborn errors of metabolism was confirmed in 35% of neonates, and 4% was suspected to have metabolic disorders. These results showed that inherited metabolic disorders are not rare. The development of a nationwide screening program for metabolic disorders is mandatory for early detection of these potentially treatable disorders.

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