Medical Genetics 11单基因遗传病(B Single gene Disorder( B
Medical Genetics 11 单基因遗传病（B） Single Gene Disorder (B)
Medical Genetics 2. Inborn Errors of metabolism Inborn errors of meta bolism are are genetic disorders in which the body cannot turn food into energy (metabolize food) normally. The disorders are usually caused by defects in the enzymes involved in the biochemical pathways that break down food components
Medical Genetics 2. Inborn Errors of Metabolism Inborn errors of metabolism are rare genetic disorders in which the body cannot turn food into energy (metabolize food) normally. The disorders are usually caused by defects in the enzymes involved in the biochemical pathways that break down food components
Medical Genetics In 1904 the doctor Archibald E. garrod described alkaptonuria a disease he classified as a lifelong congenital chemical alteration Later on in 1909 he described other diseases albinism cystinuria porphyria and pentosuria which he named inborn Errors of metabolism", Garrod 's conclusions were completely correct in relation to the genetic basis of metabolic disorders and the gene-enzyme concept
Medical Genetics In 1904 the doctor Archibald E. Garrod described alkaptonuria, a disease he classified as a lifelong congenital chemical alteration. Later on, in 1909, he described other diseases: albinism, cystinuria, porphyria and pentosuria, which he named "Inborn Errors of Metabolism". Garrod's conclusions were completely correct in relation to the genetic basis of metabolic disorders and the gene-enzyme concept
Medical Genetics The gene defect can cause a particular enzyme to be defective or missing. And because the enzyme isn't doing what it is supposed to do for the body, poor health may result
Medical Genetics The gene defect can cause a particular enzyme to be defective or missing. And because the enzyme isn't doing what it is supposed to do for the body, poor health may result
Medical Genetics Simply put enzymes help the bod y stimulating biological reactions inside cells, Enzymes are proteins that help the body use food produce energy and do work. When a particular enzyme is defective or missing then the body isn't able to do something that it should do to maintain health. The enzyme involved determines what the body can't do and what the resulting physical features are
Medical Genetics Simply put, enzymes help the body by stimulating biological reactions inside cells. Enzymes are proteins that help the body use food, produce energy, and do work. When a particular enzyme is defective or missing, then the body isn't able to do something that it should do to maintain health. The enzyme involved determines what the body can't do and what the resulting physical features are
Medical Genetics Inborn errors of metabolism affect about 1 in every 5,000 babies born some of the more familiar born errors of metabolism are cystic fibrosis, hypothyroidism phenylketonuria(PKu) and Tay- Sachs disease
Medical Genetics Inborn errors of metabolism affect about 1 in every 5,000 babies born. Some of the more familiar inborn errors of metabolism are cystic fibrosis, hypothyroidism,, phenylketonuria (PKU) and TaySachs disease
Medical Genetics The symptoms of inborn errors of metabolism vary greatly. Each one must be reviewed separately to know what the physical features are Often an infant will show signs of failure to thrive by failing to gain weight, not eating well, and generally showing developmental delay. Vomiting and diarrhea are among other symptoms that may signal the healthcare provider to test for an inborn error of metabolism
Medical Genetics The symptoms of inborn errors of metabolism vary greatly. Each one must be reviewed separately to know what the physical features are. Often, an infant will show signs of failure to thrive by failing to gain weight, not eating well, and generally showing developmental delay. Vomiting and diarrhea are among other symptoms that may signal the healthcare provider to test for an inborn error of metabolism
Medical Genetics What are the symptoms in IMD Metabolic Results in Onset Example de fect Energy Ene rgy de ficit Fatty acid oxidation de fect generation. Hypoglycemia First year of life when the baby need to generate his own(hypoke totic hypoglycemia Confusion ehergy · Acute loc .Under stress, when having other concurrent illness, URTI Intoxication, Toxicitiy to Depe nds on expos ure to toxic substance(could be early or Glutaric aciduria Type L, accumulatio· Brain late) PKU n of toxic Liver Brain: seizure, confusion, coma, motor dysfunction, Tyrosine mia me tabolites Kidne mental re tardation Liver: cirrhosis, jaundice Inability to Storage diseases in: Usually late onset Mucopolysarrchanidosis breakdown.Liver Storage takes times to accumulate and produce symptoms Glycogen storage diseases me tabolites· Muscle B Leukocytes Urea cycle Unable to convert Neurological: vomiting, coma OTC ammonia to ure a AA NH3 Citrullinemia Lactic Different disorders A Lactate(from mild to severe) Kearn-Sayre acidosis Clinical symptoms commonly specific for a particular MELAS disorder eve s Acute intoxication, Depends on specific defect Various disorders rome patie like encephalopathy
Medical Genetics Metabolic defect Results in Onset Example Energy generation •Energy deficit •Hypoglycemia •Confusion •Acute LOC •Coma •Early •First year of life when the baby need to generate his own energy •Under stress, when having other concurrent illness, URTI Fatty acid oxidation defect (hypoketotic hypoglycemia) Intoxication, accumulatio n of toxic metabolites Toxicitiy to •Brain •Liver •Kidney Depends on exposure to toxic substance (could be early or late) •Brain: seizure, confusion, coma, motor dysfunction, mental retardation •Liver: cirrhosis, jaundice Glutaric aciduria Type I, PKU Tyrosinemia Inability to breakdown metabolites Storage diseases in: •Liver •Muscle •Brain •Leukocytes Usually late onset Storage takes times to accumulate and produce symptoms Mucopolysarrcharidosis Glycogen storage diseases Urea cycle Unable to convert ammonia to urea Neurological: vomiting, coma ^^ NH3 OTC Citrullinemia Lactic acidosis Different disorders ^ Lactate (from mild to severe) Clinical symptoms commonly specific for a particular disorder Kearn-Sayre MELAS Reye’s syndrome like Acute intoxication → hepatic encephalopathy Depends on specific defect Various disorders What are the symptoms in IMD
Medical Genetics The enzyme defects that lead to the in born errors of metabolism are caused by abnormal genes. In most cases, the abnormal gene is autosomal recessive in character
Medical Genetics The enzyme defects that lead to the inborn errors of metabolism are caused by abnormal genes. In most cases, the abnormal gene is autosomal recessive in character
Classification of inborn Errors of metabolism Medice Disorders or amino acids Cystinuria nike tyrosinemia Nonketonic hyperglycinemia Maple syrup urine disease Organic acidurias Isovaleric acidemia 3-methyicrotonyCOA carboxylase deficiency 3-methylglutaconic aci demia 3-hydroxy-3-methydglutaric acidemia romanic acidemia MethyLmalonic acidemia Multiple carboxylase deficiency Glutaric acidemia, type Urea cycle defects Carbamoyl phosphate synthetase den ciency Ornithine transcar amylase deficiency Citrullinemia Arginosuccinic aciduria Argininemia Lysinuric protein intolerance ugar intolerances Classical galactosemia Galactokinase deficiency Epimerase deficiency Hereditary fructose intolerance Hereditary fructose-1.6. Diphosphetes defICIE
Medical Genetics