This makes it essential that the practicing pediatrician be familiar with the clinical presentation of these disorders. Approach to inborn errors authorstream presentation. Fortunately, with better treatments and diagnosis, the outlook has improved for. Inborn errors of metabolism iem can present as acute metabolic emergencies resulting in significant morbidity, progressive neurologic injury, or death. Early recognition of inborn errors of metabolism iem and prompt management are essential to prevent death or neurodisability diagnosis of iem in neonates is often delayed owing to nonspecific nature of clinical presentation, and unfamiliarity with diagnostic tests seek advice from local and regional clinical chemistry services. Inborn errors of metabolism arenow often referred to ascongenital metabolic diseasesor inherited metabolic diseases 3 4. One of the major milestones in the development of this branch of medicine was the description of phenylketonuria pku by folling in 1934 1, 2. Inborn errors of metabolism iems individually are rare but collectively are common. The disorders are usually caused by defects in specific proteins enzymes that help break down metabolize parts of food. Approach to patient with inborn errors of metabolism. Describe inborn errors of metabolism in neonates 2. His seminal text, inborn errors of metabolism was published in 1923.
Approach to inborn errors of metabolism introduction also known as biochemical diseases, inherited metabolic disorders are mostly single gene disorders that affect one of the biochemical processes of the body. Inborn errors of metabolism iem, although individually rare, occur in 1 out of every 1,500 births. Msud maple syrup urine disease only amino acid disorder that presents acutely in the neonatal period. Inborn errors of metabolism recognition early recognition of inborn errors of metabolism iem and prompt management are essential to prevent death or neurodisability diagnosis of iem in neonates is often delayed owing to nonspecific nature of. Many of these disorders are detected through newborn screening or clinical suspicion. He called these disorders inborn errors of metabolism.
Approach to inborn errors of metabolism presenting in the. Ppt approach to inborn errors of metabolism powerpoint presentation free to download id. The failure to effectively use this sugars accounts for the majority of the inborn errors of human carbohydrates metabolism. Ppt approach to inborn errors of metabolism powerpoint. Approach to inborn errors of metabolism for an endocrinologist. Inborn error of metabolism an overview sciencedirect.
A practical clinical approach to the recognition of inborn errors of metabolism in the young infant is presented in. If an autopsy is not permitted, request consent for premortem or immediately post. The number of diseases in humans known to be attributable to inherited point defects in metabolism now exceeds 500. Arial wingdings gungsuh clouds approach to inborn errors of metabolism goals for this lecture.
Review differential for metabolic encephalopathy in the newborn. Is the metabolic acidosis the result of abnormal losses of bicarbonate diarrhea or accumulation of acid. Inborn errors of metabolism iem are individually rare, but collectively numerous. Inborn errors of metabolism iem are a group of disorders that causes a block in a metabolic pathway leading to clinically significant consequences. Inborn errors of metabolism 159 it is important to make a specific diagnosis, even in a dying child, to help parents understand what happened and to provide information that might affect future reproductive planning. Although garrod was incorrect in his categorization of cystinuria, his insights provided the field of biochemical genetics with a solid foundation, and the list of inherited inborn errors of metabolism has rapidly grown. Started in 1995, this collection now contains 6767 interlinked topic pages divided into a tree of 31 specialty books and 732 chapters. Many of these conditions are very serious, and may even be lifethreatening. Inborn errors of metabolism university of new mexico. Trahms, in nutrition in the prevention and treatment of disease, 2001. Schafermeyer, md, facep, faap, fifem, associate chair, department of emergency medicine, carolinas medical center. Approach to inborn errors of metabolism presenting in the neonate. This article is primarily concerned with these inherited. Recognize that urea cycle disorders can result in hyperammonemia, which is a medical emergency that requires prompt diagnosis and treatment.
Approach to patient with inborn errors of metabolism dr. Inborn errors of metabolism iem are genetic disorders of intermediary metabolism that result in metabolic defects due to deficiency of enzymes, membrane transporters, or other functional proteins. Approach to inborn errors of metabolism learn pediatrics. Inborn errors of metabolism inborn errors of metabolism an inherited enzyme deficiency leading to the disruption of normal bodily metabolism accumulation of a toxic substrate compound acted. Recent advances in the diagnosis and treatment of inborn errors of metabolism have improved substantially the prognosis for many of these conditions. Hepatic inborn errors of metabolism diet restricted in tyrosine and phenylalanine. Inborn errors of metabolism presenting in neonates inborn errors of metabolism iem are disorders in which there is a block at some point in the normal metabolic pathway caused by a genetic defect of a specific enzyme.
Mannenbach, md, assistant professor, department of pediatric and adolescent medicine, mayo college of medicine, rochester, mn. Clinical approach to inborn errors of metabolism in. Laboratory diagnostic approaches in metabolic disorders. Inborn errors of metabolism university of miami health. The concept of inborn errors of metabolism iem was introduced by archibald garrod in 1909. Inborn errors of metabolism iem an indian perspective medind. Inborn errors of metabolism iem are disorders in which there is a block at some point in the normal metabolic pathway caused by a genetic defect of a specific. Individually they are rare but together they are common with a. Biomarkers in inborn errors of metabolism sciencedirect. Most are rare but some are common, for example phenylketonuria pku occurs 1 in 12,000 births 1. Dietary management, sometimes combined with pharmacological treatment, can help optimise health outcomes, making newborn screening essential. A food product that is not broken down into energy can build up in the body and cause a wide range. If your family has a history of inborn errors of metabolism, your child may be at risk for genetic conditions that can cause neurological problems.
Although the sheer number of iem is daunting, a systematic and logical approach to test selection in a patient with a clinical presentation of a metabolic defect, regardless of age, can lead to a high degree of diagnostic success. Rule out nonmetabolic causes of symptoms such as infection or asphyxia. Presentation is usually in the neonatal period or infancy but can occur at any time, even in adulthood. Inborn errors of metabolism iem are disorders in which there is a block at some point in the normal metabolic pathway caused by a genetic defect of a specific enzyme.
Pdf biochemical genetics and inborn errors of metabolism. Inborn errors of metabolism ucsf benioff childrens hospital. The major classes of inborn errors of metabolism iem and their characteristic clinical and biochemical features are described below. A free powerpoint ppt presentation displayed as a flash slide show on id. Dietary management for inborn errors of metabolism. Debra regier and holly bloom for childrens national medical center. Metabolism is a sequence of chemical reactions that take place in cells in the body. The term inborn errors of metabolism was coined by a british physician, archibald garrod 18571936, in 1908. Dietary management for inborn errors of metabolism clinical symptoms of iems may appear at the very early stages of life. Galactose galactosemia, the inability to metabolize galactose, is the most common monogenic disorder of carbohydrate metabolism, affecting 1 in every 55,000 newborns.
Garrods hypothesis a b c product deficiency substrate excess d toxic metabolite 4 5. Vahabi suspicion an important key to diagnosing iem is thinking about the possibility in the first place the symptoms. Approach to inborn errors of metabolism in pediatrics pediatric. Learn vocabulary, terms, and more with flashcards, games, and other study tools.
A snapshot summary inborn errors of metabolism iem are single gene defects that result in abnormalities in the synthesis or catabolism of proteins, carbohydrates or fats. Introduction to iem differential diagnosis of any sick neonate iem are individually rare overall incidence upto 1 in 2000 high index of suspicion for diagnosis 3. Inborn errors of metabolism iem include a broad spectrum of defects of various gene products that affect intermediary metabolism in the body, resulting in clinical disease. Many of the inborn errors of metabolism, including urea cycle defects, organic acidemias, and certain disorders of amino acid metabolism, present in the young infant with symptoms of an acute or chronic metabolic encephalopathy. Ppt inborn errors of metabolism powerpoint presentation. Easy and simple explanation of metabolic disorders, its recommended after viewing this video to read the metabolic disorders from any pediatric.
The recent application of tandem mass spectrometry tandem. He is known for work that prefigured the one geneone enzyme hypothesis, based on his studies on the nature and inheritance of alkaptonuria. Discuss advances in neonatal care of patients with inborn errors of metabolism. Discuss methods for early recognition and treatment of neonates with inborn errors of metabolism 3. Inborn errors of metabolism are inherited biochemical disorders with specific enzyme defect that interferes with the normal metabolism of protein, fat or carbohydrate. The application of tandem mass spectrometry tandem ms to newborn screening and prenatal diagnosis has enabled. Develop a basic framework for understanding inborn errors of metabolism to aid in recognition and diagnosis of these conditions. Inborn errors of metabolism iem are present at birth and persist throughout life.
Congenital metabolic disorders result from the absence or abnormality of an enzyme or its cofactor, leading to either accumulation or deficiency of a specific metabolite table 1 and table 2 and table 3 and table 4 and table 5 and table 6. Inborn errors of metabolism, encephalopathy, hyperammonemia. Inborn errors of metabolism iems are rare genetic or inherited disorders resulting from an enzyme defect in biochemical and metabolic pathways affecting proteins, fats, carbohydrates metabolism. Decreased paco2 because of compensatory hyperventilation. Hendersonhasselbach equation measures the anion gap. As a result, optimal outcomes for children with iem depend upon recognition of the signs and symptoms of metabolic disease, prompt evaluation, and referral to a center familiar with the. Approach to inborn error of metabolism in a neonate. Inborn errors of metabolism are defects in the mechanisms of the body which break down specific parts of food into chemicals the body is able to use. If you continue browsing the site, you agree to the use of cookies on this website.