Inborn errors of immunity and metabolic disorders: current understanding, diagnosis, and treatment approaches

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Pelin Teke Kisa ◽  
Nur Arslan
Keyword(s):  
Immune Deficiency ◽  
Inborn Errors Of Metabolism ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Liver Function Tests ◽  
Primary Immune Deficiency ◽  
Inborn Errors ◽  
Immunological Disorders ◽  
Organ Systems ◽  
Immunological System

AbstractInborn errors of metabolism consist of a heterogeneous group of disorders with various organ systems manifestations, and some metabolic diseases also cause immunological disorders or dysregulation. In this review, metabolic diseases that affect the immunological system and particularly lead to primary immune deficiency will be reviewed. In a patient with frequent infections and immunodeficiency, the presence of symptoms such as growth retardation, abnormal facial appearance, heart, skeletal, lung deformities, skin findings, arthritis, motor developmental retardation, seizure, deafness, hepatomegaly, splenomegaly, impairment of liver function tests, the presence of anemia, thrombocytopenia and eosinophilia in hematological examinations should suggest metabolic diseases for the underlying cause. In some patients, these phenotypic findings may appear before the immunodeficiency picture. Metabolic diseases leading to immunological disorders are likely to be rare but probably underdiagnosed. Therefore, the presence of recurrent infections or autoimmune findings in a patient with a suspected metabolic disease should suggest that immune deficiency may also accompany the picture, and diagnostic examinations in this regard should be deepened.

scholarly journals Fructose and Mannose in Inborn Errors of Metabolism and Cancer

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 479
Author(s):  
Elizabeth L. Lieu ◽  
Neil Kelekar ◽  
Pratibha Bhalla ◽  
Jiyeon Kim
Keyword(s):  
Metabolic Disease ◽  
Inborn Errors Of Metabolism ◽  
Metabolic Diseases ◽  
Treatment Options ◽  
Biochemical Properties ◽  
Biological Molecules ◽  
Diagnostic Tools ◽  
Inborn Errors ◽  
Mannose Metabolism

History suggests that tasteful properties of sugar have been domesticated as far back as 8000 BCE. With origins in New Guinea, the cultivation of sugar quickly spread over centuries of conquest and trade. The product, which quickly integrated into common foods and onto kitchen tables, is sucrose, which is made up of glucose and fructose dimers. While sugar is commonly associated with flavor, there is a myriad of biochemical properties that explain how sugars as biological molecules function in physiological contexts. Substantial research and reviews have been done on the role of glucose in disease. This review aims to describe the role of its isomers, fructose and mannose, in the context of inborn errors of metabolism and other metabolic diseases, such as cancer. While structurally similar, fructose and mannose give rise to very differing biochemical properties and understanding these differences will guide the development of more effective therapies for metabolic disease. We will discuss pathophysiology linked to perturbations in fructose and mannose metabolism, diagnostic tools, and treatment options of the diseases.

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.

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.

A Comprehensive Screening Method for Detecting Organic Acidurias and other Metabolic Diseases in Acutely Sick Infants and Children

1977 ◽  
Vol 14 (1-6) ◽  
pp. 149-156 ◽  
Author(s):  
R. A. Chalmers ◽  
R. W. E. Watts ◽  
A. M. Lawson
Keyword(s):  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Screening Method ◽  
Perinatal Period ◽  
Screening Tests ◽  
Inborn Errors ◽  
Organic Acidurias ◽  
Urinary Organic Acids ◽  
Neonates And Infants ◽  
Normal Neonate

A protocol is described for the comprehensive screening of acutely ill neonates and infants for inherited metabolic diseases, with particular reference to the organic acidurias. A group of simple initial tests provide positive pointers to metabolic disorders, leading to comprehensive screening tests for the aminoacidopathies and organic acidurias. Specimen chromatograms of urinary organic acids in the normal neonate, infant, and child, obtained using the methods described, are given and compared with that from the urine of a child with previously unreported 2-hydroxyglutaric aciduria. The place of the scheme in the management of inherited metabolic disease in the perinatal period and its relationship to other screening programmes are discussed. It is estimated that use of the protocol would allow the detection of about one-half of the known inborn errors of metabolism, including the aminoacidopathies, the organic acidurias, the hyperammonaemias, and several disorders of carbohydrate metabolism, many of which present acutely in the neonate and infant.

scholarly journals Precision of a Clinical Metabolomics Profiling Platform for Use in the Identification of Inborn Errors of Metabolism

2020 ◽  
Vol 5 (2) ◽  
pp. 342-356 ◽  
Author(s):  
Lisa Ford ◽  
Adam D Kennedy ◽  
Kelli D Goodman ◽  
Kirk L Pappan ◽  
Anne M Evans ◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Metabolic Diseases ◽  
Clinical Laboratory ◽  
Inborn Errors ◽  
Biochemical Pathways ◽  
Whole Exome ◽  
Multiple Biomarkers ◽  
Sample Testing ◽  
Precision Study ◽  
Clinical Metabolomics

Abstract Background The application of whole-exome sequencing for the diagnosis of genetic disease has paved the way for systems-based approaches in the clinical laboratory. Here, we describe a clinical metabolomics method for the screening of metabolic diseases through the analysis of a multi-pronged mass spectrometry platform. By simultaneously measuring hundreds of metabolites in a single sample, clinical metabolomics offers a comprehensive approach to identify metabolic perturbations across multiple biochemical pathways. Methods We conducted a single- and multi-day precision study on hundreds of metabolites in human plasma on 4, multi-arm, high-throughput metabolomics platforms. Results The average laboratory coefficient of variation (CV) on the 4 platforms was between 9.3 and 11.5% (median, 6.5–8.4%), average inter-assay CV on the 4 platforms ranged from 9.9 to 12.6% (median, 7.0–8.3%) and average intra-assay CV on the 4 platforms ranged from 5.7 to 6.9% (median, 3.5–4.4%). In relation to patient sample testing, the precision of multiple biomarkers associated with IEM disorders showed CVs that ranged from 0.2 to 11.0% across 4 analytical batches. Conclusions This evaluation describes single and multi-day precision across 4 identical metabolomics platforms, comprised each of 4 independent method arms, and reproducibility of the method for the measurement of key IEM metabolites in patient samples across multiple analytical batches, providing evidence that the method is robust and reproducible for the screening of patients with inborn errors of metabolism.

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.

Protein-dependent inborn errors of metabolism

2020 ◽  
pp. 1942-1984
Author(s):  
Georg F. Hoffmann ◽  
Stefan Kölker
Keyword(s):  
Amino Acids ◽  
Organic Acid ◽  
Inborn Errors Of Metabolism ◽  
Intracellular Transport ◽  
Metabolic Diseases ◽  
Dried Blood Spots ◽  
Distinct Pattern ◽  
Inborn Errors ◽  
Enzyme Defects ◽  
Specific Disorders

Protein-dependent inborn errors of metabolism are caused by inherited enzyme defects of catabolic pathways or intracellular transport of amino acids. Most result in an accumulation of metabolites upstream of the defective enzyme (amino acids and/or ammonia), causing intoxication. Protein-dependent metabolic diseases usually have a low prevalence except for some high-risk communities with high consanguinity rates. However, the cumulative prevalence of these disorders is considerable (i.e. at least >1:2000 newborns) and represents an important challenge for all public health systems. Types and clinical presentation of protein-dependent inborn errors of metabolism—this chapter discusses amino acid disorders, organic acid disorders, and urea cycle defects. The disease spectrum is broad, but follows a distinct pattern in specific disorders. Investigation and management—every infant presenting with symptoms of unexplained metabolic crisis, intoxication, or encephalopathy requires urgent evaluation of metabolic parameters, including analyses of arterial blood gases, serum glucose and lactate, plasma ammonia and amino acids, acylcarnitine profiling in dried blood spots, and organic acid analysis in urine. This chapter discusses the basic principles of acute emergency therapy and of long-term treatment, which aims principally to mitigate the metabolic consequences of enzyme deficiencies by compensating for them. Successful treatment of affected individuals is often difficult to achieve. Careful supervision in metabolic centres involving an experienced multidisciplinary team is invaluable for the best outcome.

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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