Inborn errors of metabolism - wikipedia Inborn errors of metabolism Inborn errors of metabolism Classification and external resources Specialty medical genetics ICD - 10 E70 - E90 ICD - 9 - CM 270 - 279 MedlinePlus 002438 eMedicine emerg / 768 article / 804757 MeSH D008661 ( edit on Wikidata ) Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of metabolism. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances ( substrates ) into others ( products ). In most of the disorders, problems arise due to accumulation of substances which are toxic or interfere with normal function, or to the effects of reduced ability to synthesize essential compounds. Inborn errors of metabolism are now often referred to as congenital metabolic diseases or inherited metabolic disorders. The term inborn errors of metabolism was coined by a British physician, Archibald Garrod ( 1857 -- 1936 ), in 1908. He is known for work that prefigured the `` one gene - one enzyme '' hypothesis, based on his studies on the nature and inheritance of alkaptonuria. His seminal text, Inborn Errors of Metabolism was published in 1923. Contents 1 Classification 2 Signs and symptoms 3 Diagnosis 4 Treatment 5 Epidemiology 6 References 7 External links Classification Traditionally the inherited metabolic diseases were classified as disorders of carbohydrate metabolism, amino acid metabolism, organic acid metabolism, or lysosomal storage diseases. In recent decades, hundreds of new inherited disorders of metabolism have been discovered and the categories have proliferated. Following are some of the major classes of congenital metabolic diseases, with prominent examples of each class. Many others do not fall into these categories. Disorders of carbohydrate metabolism E.g., glycogen storage disease, G6PD deficiency Disorders of amino acid metabolism E.g., phenylketonuria, maple syrup urine disease, glutaric acidemia type 1 Urea Cycle Disorder or Urea Cycle Defects E.g., Carbamoyl phosphate synthetase I deficiency Disorders of organic acid metabolism ( organic acidurias ) E.g., alcaptonuria, 2 - hydroxyglutaric acidurias Disorders of fatty acid oxidation and mitochondrial metabolism E.g., Medium - chain acyl - coenzyme A dehydrogenase deficiency ( often shortened to MCADD. ) Disorders of porphyrin metabolism E.g., acute intermittent porphyria Disorders of purine or pyrimidine metabolism E.g., Lesch -- Nyhan syndrome Disorders of steroid metabolism E.g., lipoid congenital adrenal hyperplasia, congenital adrenal hyperplasia Disorders of mitochondrial function E.g., Kearns -- Sayre syndrome Disorders of peroxisomal function E.g., Zellweger syndrome Lysosomal storage disorders E.g., Gaucher 's disease E.g., Niemann -- Pick disease Signs and Symptoms Because of the enormous number of these diseases and wide range of systems affected, nearly every `` presenting complaint '' to a healthcare provider may have a congenital metabolic disease as a possible cause, especially in childhood. The following are examples of potential manifestations affecting each of the major organ systems. Growth failure, failure to thrive, weight loss Ambiguous genitalia, delayed puberty, precocious puberty Developmental delay, seizures, dementia, encephalopathy, stroke Deafness, blindness, pain agnosia Skin rash, abnormal pigmentation, lack of pigmentation, excessive hair growth, lumps and bumps Dental abnormalities Immunodeficiency, low platelet count, low red blood cell count, enlarged spleen, enlarged lymph nodes Many forms of cancer Recurrent vomiting, diarrhea, abdominal pain Excessive urination, kidney failure, dehydration, edema Low blood pressure, heart failure, enlarged heart, hypertension, myocardial infarction Liver enlargement, jaundice, liver failure Unusual facial features, congenital malformations Excessive breathing ( hyperventilation ), respiratory failure Abnormal behavior, depression, psychosis Joint pain, muscle weakness, cramps Hypothyroidism, adrenal insufficiency, hypogonadism, diabetes mellitus Diagnosis Dozens of congenital metabolic diseases are now detectable by newborn screening tests, especially the expanded testing using mass spectrometry. This is an increasingly common way for the diagnosis to be made and sometimes results in earlier treatment and a better outcome. There is a revolutionary Gas chromatography -- mass spectrometry - based technology with an integrated analytics system, which has now made it possible to test a newborn for over 100 mm genetic metabolic disorders. Because of the multiplicity of conditions, many different diagnostic tests are used for screening. An abnormal result is often followed by a subsequent `` definitive test '' to confirm the suspected diagnosis. Gas chromatography -- mass spectrometry ( GCMS ) Common screening tests used in the last sixty years : Ferric chloride test ( turned colors in reaction to various abnormal metabolites in urine ) Ninhydrin paper chromatography ( detected abnormal amino acid patterns ) Guthrie bacterial inhibition assay ( detected a few amino acids in excessive amounts in blood ) The dried blood spot can be used for multianalyte testing using Tandem Mass Spectrometry ( MS / MS ). This given an indication for a disorder. The same has to be further confirmed by enzyme assays, IEX - Ninhydrin, GC / MS or DNA Testing. Quantitative measurement of amino acids in plasma and urine IEX - Ninhydrin post column derivitization liquid ion - exchange chromatography ( detected abnormal amino acid patterns and quantitative analysis ) Urine organic acid analysis by gas chromatography -- mass spectrometry Plasma acylcarnitines analysis by mass spectrometry Urine purines and pyrimidines analysis by gas chromatography - mass spectrometry Specific diagnostic tests ( or focused screening for a small set of disorders ) : Tissue biopsy or necropsy : liver, muscle, brain, bone marrow Skin biopsy and fibroblast cultivation for specific enzyme testing Specific DNA testing A 2015 review reported that even with all these diagnostic tests, there are cases when `` biochemical testing, gene sequencing, and enzymatic testing can neither confirm nor rule out an IEM, resulting in the need to rely on the patient 's clinical course. '' Treatment In the middle of the 20th century the principal treatment for some of the amino acid disorders was restriction of dietary protein and all other care was simply management of complications. In the past twenty years, enzyme replacement, gene therapy, and organ transplantation have become available and beneficial for many previously untreatable disorders. Some of the more common or promising therapies are listed : Dietary restriction E.g., reduction of dietary protein remains a mainstay of treatment for phenylketonuria and other amino acid disorders Dietary supplementation or replacement E.g., oral ingestion of cornstarch several times a day helps prevent people with glycogen storage diseases from becoming seriously hypoglycemic. Vitamins E.g., thiamine supplementation benefits several types of disorders that cause lactic acidosis. Intermediary metabolites, compounds, or drugs that facilitate or retard specific metabolic pathways Dialysis Enzyme replacement E.g. Acid - alpha glucosidase for Pompe disease Gene therapy Bone marrow or organ transplantation Treatment of symptoms and complications Prenatal diagnosis Epidemiology In a study in British Columbia, the overall incidence of the inborn errors of metabolism were estimated to be 40 per 100,000 live births or 1 in 1,400 births, overall representing more than approximately 15 % of single gene disorders in the population. Type of inborn error Incidence Disease involving amino acids ( e.g. PKU ), organic acids, primary lactic acidosis, galactosemia, or a urea cycle disease 24 per 100 000 births 1 in 4,200 Lysosomal storage disease 8 per 100 000 births 1 in 12,500 Peroxisomal disorder ~ 3 to 4 per 100 000 of births ~ 1 in 30,000 Respiratory chain - based mitochondrial disease ~ 3 per 100 000 births 1 in 33,000 Glycogen storage disease 2.3 per 100 000 births 1 in 43,000 References Jump up ^ `` Inborn errors of metabolism : MedlinePlus Medical Encyclopedia ''. medlineplus.gov. Retrieved 2017 - 02 - 27. Jump up ^ `` Inherited metabolic disorders - Symptoms and causes ''. Mayo Clinic. Jump up ^ Archibald Garrod. 1923. Inborn Errors of Metabolism at Electronic Scholarly Publishing site Jump up ^ Vernon, Hilary ( Jun 2015 ). `` Inborn Errors of Metabolism : Advances in Diagnosis and Therapy ''. JAMA Pediatrics. ^ Jump up to : Applegarth DA, Toone JR, Lowry RB ( January 2000 ). `` Incidence of inborn errors of metabolism in British Columbia, 1969 - 1996 ''. Pediatrics. 105 ( 1 ) : e10. doi : 10.1542 / peds. 105.1. e10. PMID 10617747. External links National Institutes of Health offers the office of rare diseases, home reference, medlineplus and health information. Inborn error of carbohydrate metabolism : monosaccharide metabolism disorders ( E73 -- E74, 271 ) Including glycogen storage diseases ( GSD ) Sucrose, transport ( extracellular ) Disaccharide catabolism Congenital alactasia Sucrose intolerance Monosaccharide transport Glucose - galactose malabsorption Inborn errors of renal tubular transport ( Renal glycosuria ) Fructose malabsorption Hexose → glucose Monosaccharide catabolism Fructose : Essential fructosuria Fructose intolerance Galactose / galactosemia : GALK deficiency GALT deficiency / GALE deficiency Glucose ⇄ glycogen Glycogenesis GSD type 0 ( glycogen synthase deficiency ) GSD type IV ( Andersen 's disease, branching enzyme deficiency ) Adult polyglucosan body disease ( APBD ) Glycogenolysis Extralysosomal : GSD type III ( Cori 's disease, debranching enzyme deficiency ) GSD type VI ( Hers ' disease, liver glycogen phosphorylase deficiency ) GSD type V ( McArdle 's disease, myophosphorylase deficiency ) GSD type IX ( phosphorylase kinase deficiency ) Lysosomal ( LSD ) : GSD type II ( Pompe 's disease, glucosidase deficiency ) Glucose ⇄ CAC Glycolysis MODY 2 / HHF3 GSD type VII ( Tarui 's disease, phosphofructokinase deficiency ) Triosephosphate isomerase deficiency Pyruvate kinase deficiency Gluconeogenesis PCD Fructose bisphosphatase deficiency GSD type I ( von Gierke 's disease, glucose 6 - phosphatase deficiency ) Pentose phosphate pathway Glucose - 6 - phosphate dehydrogenase deficiency Transaldolase deficiency 6 - phosphogluconate dehydrogenase deficiency Other Hyperoxaluria Primary hyperoxaluria Pentosuria Aldolase A deficiency Inborn error of amino acid metabolism ( E70 -- E72, 270 ) K → acetyl - CoA Lysine / straight chain Glutaric acidemia type 1 type 2 Hyperlysinemia Pipecolic acidemia Saccharopinuria Leucine 3 - hydroxy - 3 - methylglutaryl - CoA lyase deficiency 3 - Methylcrotonyl - CoA carboxylase deficiency 3 - Methylglutaconic aciduria 1 Isovaleric acidemia Maple syrup urine disease Tryptophan Hypertryptophanemia G → pyruvate → citrate Glycine D - Glyceric acidemia Glutathione synthetase deficiency Sarcosinemia Glycine → Creatine : GAMT deficiency Glycine encephalopathy G → glutamate → α - ketoglutarate Histidine Carnosinemia Histidinemia Urocanic aciduria Proline Hyperprolinemia Prolidase deficiency Glutamate / glutamine SSADHD G → propionyl - CoA → succinyl - CoA Valine Hypervalinemia Isobutyryl - CoA dehydrogenase deficiency Maple syrup urine disease Isoleucine 2 - Methylbutyryl - CoA dehydrogenase deficiency Beta - ketothiolase deficiency Maple syrup urine disease Methionine Cystathioninuria Homocystinuria Hypermethioninemia General BC / OA Methylmalonic acidemia Methylmalonyl - CoA mutase deficiency Propionic acidemia G → fumarate Phenylalanine / tyrosine Phenylketonuria 6 - Pyruvoyltetrahydropterin synthase deficiency Tetrahydrobiopterin deficiency Tyrosinemia Alkaptonuria / Ochronosis Type I tyrosinemia Type II tyrosinemia Type III tyrosinemia / Hawkinsinuria Tyrosine → Melanin Albinism : Ocular albinism ( 1 ) Oculocutaneous albinism ( Hermansky -- Pudlak syndrome ) Waardenburg syndrome Tyrosine → Norepinephrine Dopamine beta hydroxylase deficiency reverse : Brunner syndrome G → oxaloacetate Urea cycle / Hyperammonemia ( arginine aspartate ) Argininemia Argininosuccinic aciduria Carbamoyl phosphate synthetase I deficiency Citrullinemia N - Acetylglutamate synthase deficiency Ornithine transcarbamylase deficiency / translocase deficiency Transport / IE of RTT Solute carrier family : Cystinuria Hartnup disease Iminoglycinuria Lysinuric protein intolerance Fanconi syndrome : Oculocerebrorenal syndrome Cystinosis Other 2 - Hydroxyglutaric aciduria Aminoacylase 1 deficiency Ethylmalonic encephalopathy Fumarase deficiency Trimethylaminuria Inborn error of lipid metabolism : fatty - acid metabolism disorders ( E71. 3, 277.81 -- 277.85 ) Synthesis Biotinidase deficiency Degradation Acyl transport Carnitine Primary II - acylcarnitine Adrenoleukodystrophy Beta oxidation General Acyl CoA dehydrogenase Short - chain Medium - chain Long - chain 3 - hydroxy Very long - chain Mitochondrial trifunctional protein deficiency : Acute fatty liver of pregnancy Unsaturated 2, 4 Dienoyl - CoA reductase deficiency Odd chain Propionic acidemia Other 3 - hydroxyacyl - coenzyme A dehydrogenase deficiency To acetyl - CoA Malonic aciduria Aldehyde Sjögren -- Larsson syndrome Inborn error of lipid metabolism : dyslipidemia ( E78, 272.0 -- 272.6 ) Hyperlipidemia Hypercholesterolemia / Hypertriglyceridemia Lipoprotein lipase deficiency / Type Ia Familial apoprotein CII deficiency / Type Ib Familial hypercholesterolemia / Type IIa Combined hyperlipidemia / Type IIb Familial dysbetalipoproteinemia / Type III Familial hypertriglyceridemia / Type IV Xanthoma / Xanthomatosis Hypolipoproteinemia Hypoalphalipoproteinemia / HDL Lecithin cholesterol acyltransferase deficiency Tangier disease Hypobetalipoproteinemia / LDL Abetalipoproteinemia Apolipoprotein B deficiency Chylomicron retention disease Lipodystrophy Barraquer -- Simons syndrome Other Lipomatosis Adiposis dolorosa Lipoid proteinosis APOA1 familial renal amyloidosis Heme metabolism disorders ( E80, 277.1, 277.4 ) Porphyria, hepatic and erythropoietic ( porphyrin ) early mitochondrial : ALAD porphyria Acute intermittent porphyria cytoplasmic : Gunther disease / congenital erythropoietic porphyria Porphyria cutanea tarda / Hepatoerythropoietic porphyria late mitochondrial : Hereditary coproporphyria Harderoporphyria Variegate porphyria Erythropoietic protoporphyria Hereditary hyperbilirubinemia ( bilirubin ) unconjugated : Gilbert 's syndrome Crigler -- Najjar syndrome Lucey -- Driscoll syndrome conjugated : Dubin -- Johnson syndrome Rotor syndrome Inborn error of purine -- pyrimidine metabolism ( E79, 277.2 ) Purine metabolism Anabolism Adenylosuccinate lyase deficiency Adenosine Monophosphate Deaminase Deficiency type 1 Nucleotide salvage Lesch -- Nyhan syndrome / Hyperuricemia Adenine phosphoribosyltransferase deficiency Catabolism Adenosine deaminase deficiency Purine nucleoside phosphorylase deficiency Xanthinuria Gout Mitochondrial neurogastrointestinal encephalopathy syndrome Pyrimidine metabolism Anabolism Orotic aciduria Miller syndrome Catabolism Dihydropyrimidine dehydrogenase deficiency Inborn errors of steroid metabolism Mevalonate pathway HMG - CoA lyase deficiency Hyper - IgD syndrome Mevalonate kinase deficiency To cholesterol 7 - Dehydrocholesterol path : Hydrops - ectopic calcification - moth - eaten skeletal dysplasia CHILD syndrome Conradi - Hünermann syndrome Lathosterolosis Smith -- Lemli -- Opitz syndrome desmosterol path : Desmosterolosis Steroids Corticosteroid ( including CAH ) aldosterone : Glucocorticoid remediable aldosteronism cortisol / cortisone : CAH 17α - hydroxylase CAH 11β - hydroxylase both : CAH 3β - dehydrogenase CAH 21 - hydroxylase Apparent mineralocorticoid excess syndrome / 11β - dehydrogenase Sex steroid To androgens 17α - Hydroxylase deficiency 17, 20 - Lyase deficiency 3β - Hydroxysteroid dehydrogenase deficiency 17β - Hydroxysteroid dehydrogenase deficiency 5α - Reductase deficiency Pseudovaginal perineoscrotal hypospadias To estrogens Aromatase deficiency Aromatase excess syndrome Other X-linked ichthyosis Antley -- Bixler syndrome Metabolic disorders of vitamins, coenzymes, and cofactors B7 Biotin / MCD Biotinidase deficiency Holocarboxylase synthetase deficiency Other B B5 ( Pantothenate kinase - associated neurodegeneration ) B12 ( Methylmalonic acidemia ) Other vitamin Familial isolated vitamin E deficiency Nonvitamin cofactor Tetrahydrobiopterin deficiency Molybdenum cofactor deficiency Metabolism portal Retrieved from `` https://en.wikipedia.org/w/index.php?title=Inborn_errors_of_metabolism&oldid=832230782 '' Categories : Inborn errors of metabolism Medical genetics Metabolism Hidden categories : Infobox medical condition All articles with unsourced statements Articles with unsourced statements from February 2017 Pages using div col without cols and colwidth parameters Pages using Columns - list with deprecated parameters Talk Contents About Wikipedia Čeština Deutsch Español Esperanto Français Gaeilge 한국어 हिन्दी Italiano Lietuvių Bahasa Melayu Nederlands 日本 語 Polski Português Русский ไทย Türkçe Українська 中文 12 more Edit links This page was last edited on 24 March 2018, at 17 : 14. 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Question: who wrote the book inborn errors of metabolism
Answer: British physician, Archibald Garrod