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 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.

Reimbursement for Medical Foods for Inborn Errors of Metabolism

PEDIATRICS ◽  
1994 ◽  
Vol 93 (5) ◽  
pp. 860-860
Author(s):  
Keyword(s):  
Amino Acid ◽  
Metabolic Diseases ◽  
Urea Cycle ◽  
Private Insurance ◽  
Type I ◽  
Urea Cycle Disorders ◽  
Healthy Children ◽  
Inborn Errors ◽  
Medical Foods ◽  
Cycle Disorders

Inborn errors of amino acid metabolism such as phenylketonuria, maternal phenylketonuria, maple syrup urine disease, homocystinuria, methylmalonic acidemia, propionic acidemia, isovaleric acidemia and other disorders of leucine metabolism, glutaric acidemia type I and tyrosinemia types I and II, and urea cycle disorders are rare diseases that are treatable by diet. Treatment might include the restriction of one or more amino acids, the restriction of total nitrogen, or the supplementation of specific substances. Untreated, these diseases culminate in severe mental retardation or death. Once diagnosis is confirmed, treatment of amino acid and urea cycle disorders must be carefully monitored by a physician with expertise in metabolic diseases. Special medical foods, commercially available, are indispensable for the active, ongoing treatment of diagnosed amino acid and urea cycle disorders. Special medical foods would, if used as the sole dietary source, represent a hazard to affected and healthy children. US Public Law (Publ L) 100-290 defines the term medical food as ". . . a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation."1 After passage of Publ L 100-290, many states provided funding for these products through Medicaid, and most states offered assistance through Crippled Children's and Women, Infant, and Children's programs. Some states now have laws mandating private insurance coverage for special medical foods. It is the position of the American Academy of Pediatrics that special medical foods that are used in the treatment of amino acid and urea cycle disorders are medical expenses that should be reimbursed.

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.

scholarly journals Urea cycle disorder misdiagnosed as multiple sclerosis: a case report and review of the literature

2017 ◽  
Vol 31 (2) ◽  
pp. 213-217 ◽  
Author(s):  
Hussein Algahtani ◽  
Seham Alameer ◽  
Yousef Marzouk ◽  
Bader Shirah
Keyword(s):  
Multiple Sclerosis ◽  
Urea Cycle ◽  
Urea Cycle Disorder ◽  
Neurological Dysfunction ◽  
Urea Cycle Disorders ◽  
Inborn Errors ◽  
Relapsing Remitting ◽  
Wrong Diagnosis ◽  
Cycle Disorders ◽  
Intravenous Steroids

Urea cycle disorders are a group of inborn errors of metabolism caused by dysfunction of any of the six enzymes or two transport proteins involved in urea biosynthesis. In this paper, we report a patient who presented with neurological dysfunction and coma in the immediate postpartum period. She was misdiagnosed for many years as a case of multiple sclerosis. The importance of reporting this case is to illustrate that the wrong diagnosis of patients as being affected with multiple sclerosis for many years due to magnetic resonance imaging abnormalities rather than the classic relapsing–remitting nature of the disease may lead to catastrophic consequences. The patient was treated with intravenous steroids several times, which is contraindicated in patients with urea cycle disorders as it may precipitate acute hyperammonemic attacks. In addition, the management of urea cycle disorder could have started earlier and avoided multiple admissions to the intensive care unit. We believe that the presence of symmetric hyperintense insular cortical changes are seen in multiple hyperammonemic processes, and in the context of the clinical presentation and high ammonia levels can be suggestive of a urea cycle disorder. For any patient presenting with atypical clinical features, images should be reviewed and discussed in detail with an experienced neuroradiologist. In addition, the ammonia levels should be checked if a urea cycle disorder is suspected.

scholarly journals Inborn Errors of Metabolism in Adults: Two Patients with Movement Disorders Caused by Glutaric Aciduria Type 1

2020 ◽  
Vol 7 (S3) ◽  
Author(s):  
Olga Ulmanová ◽  
Lisette H. Koens ◽  
Helena Jahnová ◽  
Jeroen J. Vries ◽  
Tom J. Koning ◽  
...  
Keyword(s):  
Movement Disorders ◽  
Inborn Errors Of Metabolism ◽  
Glutaric Aciduria Type ◽  
Inborn Errors ◽  
Glutaric Aciduria Type 1 ◽  
Glutaric Aciduria

Detection of inborn errors of metabolism using GC-MS: over 3 years of experience in southern China

2015 ◽  
Vol 28 (3-4) ◽  
Author(s):  
MinYan Jiang ◽  
Li Liu ◽  
HuiFen Mei ◽  
XiuZhen Li ◽  
Jing Cheng ◽  
...  
Keyword(s):  
Amino Acid ◽  
Inborn Errors Of Metabolism ◽  
Dehydrogenase Deficiency ◽  
Southern China ◽  
Glutaric Aciduria Type ◽  
Type I ◽  
Peroxisomal Disorders ◽  
Inborn Errors ◽  
Glutaric Aciduria ◽  
Chain Acyl

AbstractInborn errors of metabolism (IEM) have been detected worldwide using gas chromatography mass spectrometry (GC-MS) since the 1980s, but few related reports exist on the incidence, spectrum, and clinical presentation features of IEM in southern China.From January 2009 to March 2012, 16,075 urine samples were collected from patients who were highly suspected of having IEM in Guangzhou Women and Children’s Medical Center. The specimens were evaluated using GC-MS.We diagnosed 303 cases of IEM by urine GC-MS analysis, including 197 cases with amino acid disorders, 86 cases with organic acidurias (OAs), 10 cases with fatty acid oxidative (FAO) disorders, and 10 cases with peroxisomal disorders. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) was the most common (153 cases), followed by methylmalonic aciduria (48 cases), urea cycle disorders (21 cases), phenylketonuria (20 cases), propionic aciduria (11 cases), X-linked adrenoleukodystrophy (10 cases), multiple carboxylase deficiency (8 cases), glutaric aciduria type I (7 cases), isovaleric aciduria (6 cases), glutaric aciduria type II (4 cases), short-chain acyl-CoA dehydrogenase deficiency (4 cases), 3-hydroxy-3-methylglutaric aciduria (3 cases), maple syrup urine disease (2 cases), very long-chain acyl-CoA dehydrogenase deficiency (1 case), malonic aciduria (1 case), mevalonic aciduria (1 case), Canavan disease (1 case), lysine protein intolerance (1 case), and medium-chain acyl-CoA dehydrogenase deficiency (1 case). The clinical and laboratory features of IEM are neurologic signs, jaundice, metabolic acidosis, ketotic hypoglycemia, and hyperammonemia.In our study, GC-MS provided a diagnostic clue to OAs, amino acid disorders, FAO, and peroxisomal disorders. Urease pretreatment is useful for the diagnosis of NICCD. In southern China, the majority of IEM were amino acid disorders and organic acid disorders. FAO disorders were relatively rare, which we need to investigate further.

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.

scholarly journals Progress and challenges in development of new therapies for urea cycle disorders

2019 ◽  
Vol 28 (R1) ◽  
pp. R42-R48 ◽  
Author(s):  
Leandro R Soria ◽  
Nicholas Ah Mew ◽  
Nicola Brunetti-Pierri
Keyword(s):  
Urea Cycle ◽  
Clinical Investigation ◽  
Urea Cycle Disorders ◽  
Preclinical Research ◽  
Inborn Errors ◽  
Gene Therapies ◽  
Treatment Focus ◽  
New Knowledge ◽  
Novel Approaches ◽  
Cycle Disorders

Abstract Urea cycle disorders (UCD) are inborn errors of metabolism caused by deficiency of enzymes required to transfer nitrogen from ammonia into urea. Current paradigms of treatment focus on dietary manipulations, ammonia scavenger drugs, and orthotopic liver transplantation. In the last years, there has been intense preclinical research aiming at developing more effective treatments for UCD, and as a result, several novel approaches based on new knowledge of the disease pathogenesis, cell and gene therapies are currently under clinical investigation. We provide an overview of the latest advances for the development of novel therapies for UCD.

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