复旦大学：《医学遗传学 Medical Genetics》课程教学资源（PPT课件讲稿）11 单基因病（B）Single Gene Disorder（B）

Medical Genetics 11单基因遗传病(B) Single gene disorder

Medical Genetics 11 单基因遗传病（B） Single Gene Disorder (B)

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 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 meta bolic disorders and the gene-enzyme concept 人La

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 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 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 inborn 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 Tay￾Sachs disease

Medical Genetics The symptoms of inborn errors of metabolism vary greatly. Each one must be reviewed separately to know what the hysical features are. often an infant wi 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 meta bolism

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 Energy de ficit .Early Fatty acid oxidation de fect generation. Hypoglycemia First year of life when the baby need to generate his own(hy poke totic hypoglyce mia) Confusion energy Acute LOC .Under stress, when having other concurre nt illness. URT Intoxication,I Toxicitiy to Depends on exposure to toxic substance(could be early or Glutaric aciduria Type 1, accumulatio rain PKU n of toxic Liver Brain: seizure, confusion, coma, motor dysfunction. Tyrosine mia me tabolites· Kidney mental retardation Liver: cirrhosis, jaundice Inability to Storage diseases in: Usually late onset Mucopolysarrcharidos breakdown|· Liver Storage takes times to accumulate and uce s Glycogen storage diseases me tabolites· Muscle Brain . Leukocytes Urea cycle Unable to convert Neurological: vomiting, coma OTC ammonia to ure a A NH3 Citrulline mia Lactic Diffe re nt disorders A Lactate (from mild to severe) Kearn-Savre acidosis Clinical symptoms commonly specific for a particular MELAS dis order Reye’s Acute intoxication Depe nds on spe cific defect Various disorders syndrome he patic like ence phalopathy

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 inborn errors of meta bolism 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 Medica DIsorders or amino acids Cystinuria Phenylketonuria Ty 们 sImi Homocyst fu na Non-ketonic hyperglycinemia Maple syrup urine disease Organic acidurias Isovaleric acidemia 3-methylcrotonmylCOA carboxylase deficiency 3 hylglutac。nic demia 3-hydroxy.3-methydgutaric acidemia Propionic acidemia MethyLmalonic academia Multiple carboxylase deficien Glutaric acidemia. type I Urea cycle defects Carbamoyl phosphate synthetase den ciency ornithine transcar amylase deficiency Citrul linemia Arginosuccinic aciduria Argininemia Lysinuric protein intolerance Sugar intolerances Classical galactosemia Galactokinase deficiency Epimerase deficiency Hereditary fructose intolerance Hereditary fructose-1.6 biphosphate se defICIEnCy

Medical Genetics