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.

Screening Urine of 3-Week-Old Newborns: Lack of Association Between Sudden Infant Death Syndrome and Some Metabolic Disorders

PEDIATRICS ◽  
1993 ◽  
Vol 91 (5) ◽  
pp. 986-988
Author(s):  
BERNARD LEMIEUX ◽  
ROBERT GIGUERE ◽  
DENIS CYR ◽  
DENIS SHAPCOTT ◽  
MARK MCCANN ◽  
...  
Keyword(s):  
Sudden Infant Death Syndrome ◽  
Infant Death ◽  
Free Amino ◽  
Inborn Errors Of Metabolism ◽  
Metabolic Disorders ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Inborn Errors ◽  
Mcad Deficiency ◽  
Single Subjects

The only genetic metabolic disorder clearly linked thus far to sudden infant death syndrome (SIDS) is medium-chain acylcoenzyme A dehydrogenase (MCAD) deficiency. There has been no evidence for an association between SIDS and other hereditary metabolic disorders. A few studies, which were often carried out retrospectively on single subjects, have involved the measurement of various metabolites including organic acids, carnitine, free amino acids, and the enzymes implicated in the oxidation of fatty acids, and these have not linked SIDS to inborn errors of metabolism. The study of Harpey et al1 reported that 15% of SIDS infants have a fatty acid β-oxidation defect.

scholarly journals Inborn Errors of Metabolism That Cause Sudden Infant Death: A Systematic Review with Implications for Population Neonatal Screening Programmes

Neonatology ◽  
2016 ◽  
Vol 109 (4) ◽  
pp. 297-302 ◽  
Author(s):  
Willemijn J. van Rijt ◽  
Geneviève D. Koolhaas ◽  
Jolita Bekhof ◽  
M. Rebecca Heiner Fokkema ◽  
Tom J. de Koning ◽  
...  
Keyword(s):  
Systematic Review ◽  
Infant Death ◽  
Neonatal Screening ◽  
Inborn Errors Of Metabolism ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Inborn Errors

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.

Prevalence of medium-chain acyl-coenzyme A dehydrogenase deficiency in the sudden infant death syndrome

1993 ◽  
Vol 122 (5) ◽  
pp. 715-718 ◽  
Author(s):  
Raanan Arens ◽  
David Gozal ◽  
Karen Jain ◽  
Shamshad Muscati ◽  
Eva T. Heuser ◽  
...  
Keyword(s):  
Sudden Infant Death Syndrome ◽  
Infant Death ◽  
Dehydrogenase Deficiency ◽  
Coenzyme A ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Medium Chain ◽  
Chain Acyl ◽  
Acyl Coenzyme A

scholarly journals 221 newborn-screened neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency: Findings from the Inborn Errors of Metabolism Collaborative

2016 ◽  
Vol 119 (1-2) ◽  
pp. 75-82 ◽  
Author(s):  
Kristi Bentler ◽  
Shaohui Zhai ◽  
Sara A. Elsbecker ◽  
Georgianne L. Arnold ◽  
Barbara K. Burton ◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Dehydrogenase Deficiency ◽  
Coenzyme A ◽  
Inborn Errors ◽  
Medium Chain ◽  
Chain Acyl ◽  
Acyl Coenzyme A

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.

The Complex Relationship of Genetics, Groups, and Health: What it Means for Public Health

2002 ◽  
Vol 30 (2) ◽  
pp. 290-297 ◽  
Author(s):  
Ellen Wright Clayton
Keyword(s):  
Public Health ◽  
Clinical Utility ◽  
Clinical Care ◽  
Health Sector ◽  
Sudden Infant Death ◽  
Acid Oxidation ◽  
Sudden Infant ◽  
The Public ◽  
Metabolic Defects ◽  
Relationship Of

Genetics offers real opportunities for public health actors. Increased understanding of genetics will illuminate some of the factors that affect disease and, in many cases, will lead to more effective treatments. The recognition that phenylketonuria was caused by a metabolic defect that led to the accumulation of toxic levels of phenylalanine, an elevation that could largely be averted by adopting a low-phenylalanine diet, is an early example. Some cases of what was thought to be Sudden Infant Death Syndrome, a diagnosis used when no etiology is known, now appear to have been caused by metabolic defects in fatty acid oxidation and sodium channel defects. One of the tasks that has already been undertaken by the public health sector is to ensure that genomic information is incorporated into clinical care when the robusmess of findings and their clinical utility have been well defined.

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