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Inborn error of metabolism
Classification and external resources
Image:Metabolic pathways small.png
A few of the metabolic pathways in a cell. Metabolites are shown as dots and enzyme reactions as lines.
ICD-10 E70.-E90.
ICD-9 270-279
MedlinePlus 002438
eMedicine emerg/768 
MeSH D008661

Inborn errors of metabolism comprise a large class of genetic diseases involving disorders of metabolism. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings E00-E35 - Endocrine diseases (E00-E07 Thyroid gland / Thyroid hormone ( Congenital iodine-deficiency syndrome ( E00-E35 - Endocrine diseases (E00-E07 Thyroid gland / Thyroid hormone ( Congenital iodine-deficiency syndrome ( The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Genetics (from Ancient Greek grc-Latn genetikos, “genitive” and that from grc-Latn genesis, “origin” a discipline of Biology, is A disease is an abnormal condition of an organism that impairs bodily functions and can be deadly Metabolism is the set of Chemical reactions that occur in living Organisms in order to maintain Life. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substrates) into others (products). History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins A product is a substance that forms as a result of a Biological - or Chemical reaction. 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 diseases, and these terms are considered synonymous.

The term inborn error of metabolism was coined by a British physician, Archibald Garrod (1857-1936), in the early 20th century (1908). Sir Archibald Edward Garrod was an English Physician who pioneered the field of inborn errors of metabolism. He is known for the "one gene, one enzyme" hypothesis, which arose from his studies on the nature and inheritance of alkaptonuria. Alkaptonuria ( black urine disease or alcaptonuria) is a rare inherited genetic disorder of Tyrosine metabolism His seminal text, Inborn Errors of Metabolism was published in 1923.

Contents

Major categories of inherited metabolic diseases

Traditionally the inherited metabolic diseases were categorized as disorders of carbohydrate metabolism, amino acid metabolism, organic acid metabolism, or lysosomal storage diseases. Carbohydrates (from ' Hydrates of Carbon ' or saccharides ( Greek σάκχαρον meaning " Sugar " are the most In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this An organic acid is an Organic compound with Acidic properties The lysosomal storage diseases are a group of over forty human Genetic disorders that result from defects in lysosomal function 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. ICD-10 codes are provided where available. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases

Manifestations and presentations

Because of the enormous number of these diseases and wide range of systems affected, nearly every "presenting complaint" to a doctor 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:

Diagnostic techniques

Because of the multiplicity of conditions, many different diagnostic tests are used for screening. Growth failure is a medical term for a pattern of a child's growth which is poorer than normal for age sex stage of maturation and genetic height expectation Failure to thrive (FTT is a medical term which denotes poor weight gain and physical growth failure over an extended period of time in Infancy. Intersexuality is the state of a living thing of a gonochoristic species whose Sex chromosomes, Genitalia, and/or Secondary sex characteristics Puberty is described as delayed when a boy or girl has passed the usual age of onset of Puberty with no physical or hormonal signs that it is beginning Precocious puberty (La pubertas praecox) is an unusually early onset of Puberty, the process of sexual maturation triggered by the brain or exogenous chemicals which Developmental disability is a term used to describe life-long disabilities attributable to mental and/or physical or combination of mental and physical impairments An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting Dementia (from Latin de- "apart away" + Mens ( genitive mentis) "mind" is the progressive decline Encephalopathy /ɛnˌsɛfəˈlɒpəθi/ literally means Disease of the Brain. A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain Blindness is the condition of lacking Visual perception due to Physiological or Neurological factors A rash is a change of the Skin which affects its color appearance or Texture. For the drug referred to as "pigment" see Black tar heroin. Hirsutism (from Latin hirsutus = shaggy hairy is defined as excessive and increased Hair growth in women in locations where the occurrence of Terminal In Medicine, immunodeficiency (or immune deficiency) is a state in which the Immune system 's ability to fight Infectious disease is compromised Thrombocytopenia (or -paenia, or thrombopenia in short is the presence of relatively few Platelets in Blood. Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative The spleen is an organ found in all Vertebrate animals In humans the spleen is located in the abdomen of the body where it functions in the destruction of redundant Red A Lymph node ( lɪmf noʊd is an organ consisting of many types of cells and is a part of the Lymphatic system. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled Vomiting (also called throwing up, emesis) is the forceful expulsion of the contents of one's Stomach through the Mouth and sometimes the In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea Abdominal pain can be one of the Symptoms associated with transient disorders or serious disease Urination, also known as micturition, voiding, and more rarely emiction, is the process of disposing Urine from the Urinary bladder Renal failure or kidney Dehydration ( hypohydration) is the removal of Water ( hydro in ancient Greek) from an object Oedema (or Edema in American English formerly known as dropsy or hydropsy, is the increase of Interstitial fluid in any organ &mdash swelling In Physiology and Medicine, hypotension refers to an abnormally low Blood pressure. Heart failure is a Cardiac condition that occurs when a problem with the structure or function of the Heart impairs its ability to supply Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply Hepatomegaly is the condition of having an enlarged Liver. It is a nonspecific medical sign having many causes which can broadly be broken down into Infection Jaundice, also known as icterus (attributive adjective "icteric" is yellowish discoloration of the Skin, sclerae (whites of the eyes Liver failure is the inability of the Liver to perform its normal synthetic and metabolic function as part of normal physiology A congenital disorder is a disease or disorder that is present at birth In Medicine, hyperventilation (or overbreathing) is the state of Breathing faster and/or deeper than necessary bringing about lightheadedness and other Respiratory failure is a medical term for inadequate Gas exchange by the Respiratory system. Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression Psychosis (from the Greek ψυχή "psyche" for mind or soul and -οσις "-osis" for abnormal condition with adjective psychotic Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the Hypothyroidism is the disease state in humans and animals caused by insufficient production of Thyroid hormone by the Thyroid gland. Adrenal insufficiency is a condition in which the Adrenal glands located above the Kidneys do not produce adequate amounts of steroid hormones (chemicals produced by the Hypogonadism is a medical term for a defect of the Reproductive system that results in lack of function of the Gonads ( ovaries or testes) Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc A diagnostic test is any kind of Medical test performed to aid in the Diagnosis or detection of disease An abnormal result is often followed by a subsequent "definitive test" to confirm the suspected diagnosis.

Common screening tests used in the last sixty years:

Specific diagnostic tests (or focused screening for a small set of disorders):

Newborn screening

Dozens of congenital metabolic diseases are now detectable by newborn screening tests, especially the expanded testing using mass spectrometry. The ferric chloride test is used to determine the presence or absence of Phenols in a given sample Ninhydrin (triketohydrindene hydrate is a chemical used to detect Ammonia or primary and secondary Amines When reacting with these free amines a deep blue or Paper chromatography is an analytical technique for separating and identifying mixtures that are or can be coloured especially Pigments This can also be used In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this The Guthrie test, also known as the Guthrie bacterial inhibition assay, is a medical test performed on newborn infants to detect Phenylketonuria, an An organic acid is an Organic compound with Acidic properties Mass spectrometry is an analytical technique that identifies the chemical composition of a compound or sample based on the Mass-to-charge ratio of charged particles A biopsy (in Greek: βίος life and όψη look/appearance is a Medical test involving the removal of cells or tissues An autopsy, also known as a post-mortem examination, necropsy, or obduction, is a Medical procedure that consists of a thorough Examination The liver is a vital organ in the human body and is present in Vertebrates and some other animals Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain Bone marrow is the flexible tissue found in the hollow interior of Bones In adults marrow in large bones produces new Blood cells It constitutes 4% of Newborn screening is the process of testing newborn babies for treatable genetic, endocrinologic, metabolic and hematologic diseases This is an increasingly common way for the diagnosis to be made and sometimes results in earlier treatment and a better outcome.

Management

 Please help improve this section by expanding it.
Further information might be found on the talk page or at requests for expansion.

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 last two decades, enzyme replacement, gene transfer, and organ transplantation have become available and beneficial for many previously untreatable disorders. Some of the more common or promising are listed.

Resources

For clinicians and scientists in the field of inborn errors of metabolism, good resources include books by Scriver [1]. Fernandes [2], Clarke [3], Blau (diagnosis) [4], Blau (treatment) [5], Lyon [6], Nyhan [7], Hoffmann [8] and Zschocke [9]. Other ressources include genetests, orphanet, OMIM, Metab-L,societies such as the SSIEM, the SIMD and links therein. Metab-L is an Electronic mailing list on Inborn errors of metabolism (IEM that has acquired some notability among specialists in that field of medicine For medical students and clinicians looking for overviews of the field, such reviews can be found on pubmed and in good pediatric textbooks (e. g. articles by Saudubray[10], Ellaway[11], Raghuveer[12] or Burton[13] and textbooks by Hay[14] or Behrman[15]).

For patients, their families or other individuals seeking good information and support groups, the National Institutes of Health offers the office of rare diseases, genetics home reference, medlineplus and health information. "NIH" redirects here For other meanings of NIH see NIH (disambiguation. The National Human Genome Research Institute hosts an information center, a section for patients and the public and additional educational resources. Support groups can be found at NORD, Genetic Alliance and Orphanet. The genetic education center at the KUMC has many more useful links.

References

  1. ^ Charles Scriver, Beaudet, A. Charles Robert Scriver, CC, GOQ, MDCM FRS FRSC (born November 7, 1930) is an eminent Canadian Pediatrician L. , Valle, D. , Sly, W. S. , Vogelstein, B. , Childs, B. , Kinzler, K. W. (accessed 2007). The Online Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill. - Summaries of 255 chapters, full text through many universities. There is also the OMMBID blog.
  2. ^ Fernandes, J. ; Saudubray, J. M. ; van den Berghe, G. ; Walter, J. H. (2006). Inborn Metabolic Diseases : Diagnosis and Treatment, 4th, Springer, 561 p.  
  3. ^ Clarke, J. T. R. (2005). A Clinical Guide to Inherited Metabolic Diseases, 3rd, Cambridge: Cambridge University Press, 358 p. DOI:10.2277/0521614996. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. ISBN 978-0521614993.  
  4. ^ Blau, N. ; Duran, M. ; Blaskovics, M. E. ; Gibson, K. M. (2002). Physician's Guide to the Laboratory Diagnosis of Metabolic Diseases, 2nd, Springer, 716 p. ISBN 978-3-540-42542-7.  
  5. ^ Blau, N; Hoffmann, G. F. ; Leonard, J. ; Clarke, J. T. R. (2006). Physician's Guide to the Treatment And Follow-up of Metabolic Diseases, 1st, Springer, 416 p. ISBN 3-540-22954-X.  
  6. ^ Lyon, G. ; Kolodny, E. H. ; Pastores, G. (2006). Neurology of Hereditary Molecular & Metabolic Disease of Children, 3rd, McGraw-Hill Professional, 500p.  
  7. ^ Nyhan, W. L. ; Barshop, B. ; Ozand, P. T. (2005). Atlas of Metabolic Diseases, 2nd, Oxford University Press, 800 p.  
  8. ^ Hoffmann, G. F; Nyhan, W. L. ; Zschocke, J. ; Kahler, S. G; Mayatepek, E. (2001). Inherited Metabolic diseases. Lippincott Williams & Wilkins, 448 p.  
  9. ^ Zschocke, J; Hoffmann, G. F. (2004). Vademecum Metabolicum, 2nd, Schattauer GmbH, 176 p.  
  10. ^ Saudubray J, Sedel F, Walter J. "Clinical approach to treatable inborn metabolic diseases: an introduction". J Inherit Metab Dis 29 (2-3): 261-74. PMID 16763886.  
  11. ^ Ellaway C, Wilcken B, Christodoulou J (2002). "Clinical approach to inborn errors of metabolism presenting in the newborn period". J Paediatr Child Health 38 (5): 511-7. doi:10.1046/j.1440-1754.2002.00047.x. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12354271.  
  12. ^ Raghuveer T, Garg U, Graf W (2006). "Inborn errors of metabolism in infancy and early childhood: an update". Am Fam Physician 73 (11): 1981-90. PMID 16770930.  
  13. ^ Burton B (1998). "Inborn errors of metabolism in infancy: a guide to diagnosis". Pediatrics 102 (6): E69. doi:10.1542/peds.102.6.e69. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 9832597.  
  14. ^ Hay, W. H. , Jr. ; Levin, M. J. ; Sondheimer, J. M. ; Deterding, R. R. (2006). Current Pediatric Diagnosis and Treatment, 18th ed. , McGraw-Hill, 1306 p.  
  15. ^ Behrman, R. E. ; Kliegman, R. M. ; Jenson, H. B. (2004). Nelson Textbook of Pediatrics, 17th ed. , Elsevier, 2672 p.  
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