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 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.

Inborn Errors of Metabolism

1980 ◽  
Vol 2 (6) ◽  
pp. 175-181
Author(s):  
George M. Komrower
Keyword(s):  
Neurospora Crassa ◽  
Inborn Error ◽  
Inborn Errors Of Metabolism ◽  
Metabolic Disorders ◽  
Homogentisic Acid ◽  
Turn Of The Century ◽  
Inborn Errors ◽  
The Family ◽  
The One ◽  
Biochemical Abnormalities

Around the turn of the century Garrard established the concept of an inborn error of metabolism using his study on alcaptonuria to exemplify his hypothesis that a considerable number of metabolic disorders with clearly defined clinical, pathologic, and biochemical abnormalities arise because an enzyme governing a single metabolic step is either reduced in activity or missing altogether. He pointed out the familial distribution of alcaptonuria and later showed that the inheritance could be explained on mendelian principles, ie, the affected individual was homozygous for the abnormal gene and that the inheritance was recessive, both parents being heterozygous for the disorder. He suggested that the accumulation of homogentisic acid in alcaptonuria was evidence that this substance is a normal metabolite in the degradation of tyrosine and attributed this accumulation to a failure of oxidation of homogentisic acid. In addition to alcaptonuria he described cystinunia, pentosuria, and albinism. This work was the forerunner of the classic studies of Beadle and Tatum on mutants of Neurospora crassa which led to the one gene-one enzyme concept. DETECTION Different groups require special attention: the family at risk because of previously affected individuals, those with unusual features suggestive of metabolic disorders, and sick newborns. Screening of normal newborns requires a different approach.

Phenylketonuria—1986

1986 ◽  
Vol 7 (9) ◽  
pp. 269-275
Author(s):  
Harvey L. Levy
Keyword(s):  
Metabolic Disorders ◽  
Genetic Disorder ◽  
Newborn Infants ◽  
Biochemical Screening ◽  
Clinical Expression ◽  
Inborn Errors ◽  
Biochemical Basis ◽  
Phenylalanine Level ◽  
Phenylalanine Metabolism ◽  
The Many

Phenylketonuria (PKU) has been aptly described as the "epitome of human biochemical genetics." In so distinguishing PKU among the many metabolic disorders now known, Scriver and Clow identified several categories in which this inborn error of metabolism is singularly prominent. First and foremost, PKU represents a fusion of effort between public health and genetics. It is the major genetic disorder in which treatment can prevent the clinical expression of disease and for which routine biochemical screening of newborn infants was developed. It remains the model for such screening. Second, PKU is the prime example of the importance of understanding as completely as possible the biochemical basis of a metabolic disorder. The detailed understanding of phenylalanine metabolism that arose from studies spawned by PKU led to the recognition of "new" metabolic disorders that relate to PKU in their capacity to increase the phenylalanine level but that involve a different category of metabolism and require very different treatment. Third, PKU represents an important link between obstetrics and pediatrics. The threat to the fetus from PKU in the pregnant woman (maternal PKU) must be met by special dietary care throughout the pregnancy. This is, perhaps, only the first of other maternal inborn errors that will require similar intervention during pregnancy.

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.

Cellular metabolism

2021 ◽  
pp. 105-194
Keyword(s):  
Electron Transport Chain ◽  
Inborn Errors Of Metabolism ◽  
Krebs Cycle ◽  
Cellular Metabolism ◽  
Atp Synthesis ◽  
The Body ◽  
Clinical Aspects ◽  
Inborn Errors ◽  
Transport Chain ◽  
Cellular Compartments

‘Cellular metabolism’ addresses the major biochemical pathways and processes of the cells of the body. These include the central metabolic pathways involved in energy production: the tricarboxylic acid or Krebs cycle, and ATP synthesis through the electron transport chain and oxidative phosphorylation (chemiosmotic theory). Metabolism of each of the major fuel sources is considered: lipids, carbohydrates, and proteins, including energy storage as fat and glycogen, and excretion of nitrogen via the urea cycle. The different cellular compartments for metabolism are explored, as is the integration and regulation of the metabolic processes in a number of conditions such as fasting and starvation, exercise, pregnancy, and diabetes. Finally in this chapter the clinical aspects of metabolism are discussed, including energy balance and nutrition, obesity, and inborn errors of metabolism.

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.

PHENYLKETONURIA: A STUDY OF HUMAN BIOCHEMICAL GENETICS

PEDIATRICS ◽  
1966 ◽  
Vol 38 (2) ◽  
pp. 173-184
Author(s):  
David Yi-Yung Hsia
Keyword(s):  
Royal College ◽  
Inborn Errors Of Metabolism ◽  
Metabolic Disorders ◽  
Vital Role ◽  
Biochemical Genetics ◽  
Inborn Errors ◽  
Research Fellow ◽  
Johnson Company

ONE of the privileges extended to me upon receiving the E. Mead Johnson Award is to have an opportunity to express in public my gratitude to the several teachers who have contributed so heavily to my development. First and foremost, I want to thank Dr. Sydney Gellis, who first took me on as a research fellow, subsequently fired in me an excitement and enthusiasm for research, and has remained through the years a loyal friend and colleague. Next, I want to thank Dr. Charles Janeway who had the vision of urging me to become interested in the then embryonic field of "inborn errors of metabolism." In the pursuit of this interest, I want to thank Dr. Eugene Knox for teaching me the biochemistry and Professor Lionel Penrose for teaching me the genetics which subsequently led to the work on phenylketonuria. Finally, the late Dr. John Bigler and Dr. Robert Lawson gave me the encouragement and the freedom to pursue these studies in Chicago. On this occasion I would also like to express my appreciation to the Mead Johnson Company for having provided me with my first fellowship, which permitted me to go into research, and also for having manufactured the product which has played such a vital role in our understanding of phenylketonuria. The concept of "inborn errors of metabolism" was first suggested by Sir Archibald Garrod in 1908. In the Croonian Lectures delivered at the Royal College of Physicians, he suggested that four metabolic disorders—albinism, alkaptonuria, cystinuria, and pentosuria—had certain features in common.

DIAGNOSIS AND TREATMENT: SOME DISEASES, SYNDROMES, AND CONDITIONS ASSOCIATED WITH AN UNUSUAL ODOR

PEDIATRICS ◽  
1968 ◽  
Vol 41 (5) ◽  
pp. 993-995
Author(s):  
Thomas E. Cone
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Acid Metabolism ◽  
Clinical Medicine ◽  
The Body ◽  
Ayurvedic Medicine ◽  
Precise Description ◽  
Inborn Errors ◽  
Diagnostic Significance ◽  
Sense Of Smell ◽  
Almost All

This Quotation from the writings of one of the founders of ancient Hindu or Ayurvedic medicine, is evidence that Suśruta was aware of the diagnostic significance of odors in many diseases. For most contemporary physicians an awareness of the importance of the sense of smell in clinical medicine was rekindled largely by the discovery of phenylketonuria by Følling ill 1934.2 He, as has almost every other student of this disease, called attention to a distinctive odor of patients with PKU. With the burgeoning of our knowledge of inborn errors of metabolism during the last decade, we are now aware of at least five additional conditions in which the patient's odor is unusual; these conditions include disorders of amino acid as well as fatty acid metabolism. ODORS IN CLINICAL MEDICINE The quality or character of odors described ill clinical medicine for the same disease varies from author to author. Although an odor may be defined as a volatile emanation that is perceived by the sense of smell, the precise description of a particular odor is extremely difficult. This may be because most of us, unlike almost all other mammals, pay little attention to the odors around us. It is not that we are anosmic but rather that our faculty for discniminating smell in clinical practice has atrophied from disuse. Sources of Patients' Odors Odors arise chiefly from the secreta and excreta of the body: sweat, sebum from the skin; secreta from the nose, mouth, throat, bronchi, and lungs; urine, stool and vaginal discharges; wound suppuration; and from necrotic tissue.

scholarly journals Screening for Inherited Metabolic Disorders: A New Look at Metabolic Screening Tests

1972 ◽  
Vol 9 (1-6) ◽  
pp. 103-108 ◽  
Author(s):  
J. W. T. Seakins ◽  
Makbule Haktan ◽  
B. C. Andrew ◽  
R. S. Ersser
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Metabolic Disorders ◽  
Screening Tests ◽  
Inborn Errors ◽  
Inherited Metabolic Disorders ◽  
Metabolic Screening ◽  
New Look

Simple methods for the detection of inborn errors of metabolism which result in the accumulation of metabolites in blood or urine are described and the significance of abnormal findings reviewed.

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