Inborn errors of metabolism are inherited biochemical disorders with specific enzyme defect that interferes with the normal metabolism of protein, fat or carbohydrate. They include phenylketonuria pku and maple syrup urine disease. Metabolic disorders handbook human genetics society of. Macdonald a, van rijn m, feillet f, lund am, bernstein l, bosch am, et al. Protein disorders iem include inherited biochemical disorders in which specific enzyme defects interfere with the normal metabolism of exogenous. Clinical manifestations rash, light sensitivity cerebellar ataxia dermatitis mental retardation treatment dietary niacin is given. Approach to inborn errors of metabolism learn pediatrics. Because these disorders cause symptoms early in life, newborns are routinely screened for several common amino acid disorders. Based on individual nutritional needs infants low protein formula supplemented with breast milk or regular infant formula supplement arginine and citrulline children liver transplantno need for protein restriction no liver transplant in mild cases slowly increasing protein tolerance. Protein is a key constituent of most foods we eat, including meat, beans, milk products and grains. Although previously treatment was restricted to infancy and early childhood, lifelong therapy is now recommended given the emergence of numerous behavioral and psychiatric phenotypes in. The study of disorder of protein metabolism has been mentioned in research publications which can be found using our bioinformatics tool below.
An overall scheme of the metabolism of phenylalanine and tyrosine and the associated. In healthy people it is 4,46,6 mmoll 70110 mgdl sucrose is the organic compound commonly known as table sugar and sometimes called saccharose. Metabolism is the complex set of chemical reactions that your body uses to maintain. Subgroups disorders of protein metabolism disorders of amino acid metabolism urea cycle defects organic acidemias disorders of carbohydrate metabolism. The disorders of carbohydrate and lipid metabolism caused by diabetes have both direct and indirect effects on lipoprotein metabolism. It is caused by a deficiency of the protein citrin which is necessary for many metabolic processes. Some of the sections are specific to the condition that you or your child has. Synthesis of glycogen starts at protein primer glycogenin straight chains.
If persistent vomiting occurs in the neonatal period, it usually signals significant underlying disease. The objective of the phenylalaninerestricted diet is to provide sufficient phenylalanine for growth, while maintaining serum phenylalanine levels within a target range of 26 mgdl throughout the lifespan 7, 8. Disorders of carbohydrate metabolism result from disruption in the synthetic or catabolic pathways of various categories of carbohydrates, with fructose, galactose, and glycogen being the most common groups. This condition causes an inability to break down a particular kind of fat, which accumulates in the liver, spleen, and bone. Nutrition support for inborn errors of protein metabolism dr. Dec 07, 2018 methionine is an essential amino acid and provides the most common starting codon for protein translation. Strictly speaking, neurometabolic diseases arise from genetic deficiency of intermediary metabolism enzymes, in contrast with mutations in genes encoding cytostructural proteins or proteins involved in cell division, immunity. Genetic disorders that affect the metabolism of food food that is not broken down properly may produce chemicals that build up in various parts of the body, causing medical problems and learning problems missing or defective enzymes proteins necessary to metabolize food inherited disorders each parent is a carrier of a noneach parent.
Jul 12, 2017 inherited metabolic disorders refer to different types of medical conditions caused by genetic defects most commonly inherited from both parents that interfere with the bodys metabolism. Pem is a spectrum of diseases whose essential feature is. Decreased paco2 because of compensatory hyperventilation. Metabolic disease disorders of amino acid metabolism. Your body can use this fuel right away, or it can store the energy in your body tissues, such as your. Pku was first identified in 1934 by asbjorn folling when he found elevated phenylketones in the urine of two siblings with intellectual. Nov, 2019 one group of these disorders is amino acid metabolism disorders. Adherence issues in inherited metabolic disorders treated by low natural protein diets. Organic acid disorders most are disorders of amino acid metabolism some caused by mutations in cofactors biotinidase most are enzyme defects isovaleric acidemia, propionic acidemia, me thylmalonic acidemia treatment diet for life. Is the metabolic acidosis the result of abnormal losses of bicarbonate diarrhea or accumulation of acid. Infants with protein metabolism disorders cannot drink human milk because it also contains proteins and amino acids that cannot be metabolized.
Disorders of amino acid metabolism phenylketonuria pku maple syrup urine disease msud homocystinuria hcy citrullinemia cit argininosuccinic aciduria asa tyrosinemia type i tyr i disorders of fatty acid metabolism medium chain acylcoa dehydorgenase deficiencey mcad trifunctional protein deficiency tfp very longchain acylcoa. Get an overview of the disorders of carbohydrate metabolism and amino acid metabolism and learn more about glycogen storage disease, galt deficiency, phenylketonuria, homocystinuria, and alkaptonuria. Phenylketonuria pku hyperphenylalanemia is an amino acid disorder caused by decreased activity, impaired synthesis. Pdf biomarkers to identify protein metabolism impairment in. The steps of protein synthesis include transcription, translation, and post translational modifications. Disorders of incomplete metabolism of phenylalanine and tyrosine are outstanding examples of geneenzyme interrelationships. Replacement therapy correction of underlying cause if possiblecorrection of underlying cause if possible iron excess more dangerous than iron deficiency. Metabolic disease metabolic disease disorders of amino acid metabolism. Disorders of metabolism of proteins, lipids, carbohydrates nucleid. Pyruvate dehydrogenase complex deficiency pdcd and phenylketonuria pku are genetic disorders. Pdf macronutrient metabolism in starvation and stress. The liver is also the major site of amino acid degradation, and partially oxidizes most amino acids, converting the carbon skeleton to glucose, ketone bodies, or co2.
Disorders of protein metabolism symposiumorganized by theassociation ofclinical pathologists delivered in londonon 28 and29 october 1974 editedby g. These conditions may also be called inborn errors of metabolism. Ferguson, in biomarkers in inborn errors of metabolism, 2017. Clinical features include various combinations of hypoglycemia low blood sugar, liver. Also in supply the nitrogen for the dna and rna genetic materials and the energy production. Protein metabolic disorders are inherited inborn error of metabolism. Disorders of metabolism of proteins, lipids, carbohydrates, nucleid acid. Newborn screening for disorders of amino acid metabolism. Phenylpyruvic oligophrenia, alkaptonuria, tyrosyluria, and albinism have been discussed and an attempt has been made to correlate clinical findings with biochemical alterations. Amino acids are building blocks that join together to form proteins. Metabolic disease disorders of carbohydrate metabolism.
Inborn errors of metabolism inherited metabolic disorders are often treated with nutritional counseling and support, periodic assessment, physical therapy, and other supportive care options. Metabolic disease metabolic disease disorders of carbohydrate metabolism. Lipoprotein metabolism and the treatment of lipid disorders. Chemicals in your digestive system break the food parts down into sugars and acids, your bodys fuel. Disorders like phenylketonuria pku and maple syrup urine disease cause problems with how your body uses proteins. Inherited metabolic disorders symptoms and causes mayo clinic. One group of these disorders is amino acid metabolism disorders. Disease bioinformatics research of disorder of protein metabolism has been linked to amyloidosis, metabolic diseases, nervousness, plaque, amyloid, hereditary amyloidoses. During transcription, rna polymerase transcribes a coding region of the dna in a cell producing a sequence of rna. Differentiate between glucogenic and ketogenic amino acids. Oct 31, 2017 metabolism is the chemical process your body uses to transform the food you eat into the fuel that keeps you alive. Metabolic disorders constitute an expanding group of flux diseases that includes heterogeneous conditions see table 10. Most people with inherited metabolic disorders have a defective gene that results in an enzyme deficiency. Inherited metabolic disorders symptoms and causes mayo.
Inherited metabolic disorders are genetic conditions that result in metabolism problems. In the neonatal onset type of cit ii, bile flow is blocked. Specifically, the metabolic diseases of muscle interfere with chemical reactions involved in drawing energy from food. The inability to effectively use metabolites of carbohydrates accounts for the majority of these disorders. Disorders of protein metabolism journal of clinical pathology. Disorders caused by a proteindeficient diet occurring. The differential diagnosis of elevated plasma methionine includes tyrosinemia type i due to liver disease, citrin deficiency see urea cycle disorders homocystinuria, and the disorders of homocysteine synthesis. Protein involved in iron metabolism disorder hfe inherited metabolic disorders are one cause of metabolic disorders, and occur when a defective gene causes an enzyme deficiency. The liver is the major site of amino acid metabolism in the body and the major site of urea synthesis.
The prognosis of patients with a disease in this family of disorders ranges from benign to lifethreatening. Iron metabolism disorders most common form of anemia symptom of pathologic process primary manifestation is hematologic treatment requires. Carbohydrate metabolism disorders are errors of metabolism that affect the catabolism and anabolism of carbohydrates. Overview of amino acid metabolism disorders childrens. If you have one of these disorders, your body may have trouble breaking down certain amino acids.
Metabolic disorders are usually defined as inborn errors of metabolism, encompassing deficiencies in enzymes involved in the metabolism of carbohydrates, amino acids derived from proteins, and fatty acids liberated from lipids. Also known as biochemical diseases, inherited metabolic disorders are mostly single gene disorders that affect one of the biochemical processes of the body. Acquired metabolic disorder treatment will include normalizing the metabolic balance by both reversing the cause and administering medications. Twenty amino acids, including nine that cannot be synthesized in humans and must be obtained through food, are involved in metabolism. Agarose gel electrophoresis in determination of specific proteins, electroimmunoassay as supplement to, 22.
Pyruvate dehydrogenase complex deficiency and phenylketonuria. Reassure parents that this is a benign condition and should resolve. Much of the body is made of protein, and these proteins. Disorders of carbohydrate metabolism and amino acid metabolism. Disorders that affect the metabolism of amino acids include phenylketonuria, tyrosinemia, homocystinuria, nonketotic hyperglycinemia, and maple syrup urine disease. These disorders are autosomal recessive, and all may be diagnosed by analyzing amino acid concentrations in body fluids.
Food is made up of proteins, carbohydrates, and fats. An inherited enzyme deficiency leads to the disruption of normal. Radha rama devi clinical geneticist and pediatrician. Amino acids phenylketonuria, maple syrup urine disease. During protein metabolism, some of the protein will converted into glucose through gluconeogenesis process. Major index which describes metabolism of carbohydrates, is a sugar level in blood. Hereditary disorders of amino acid processing metabolism can result from defects either in the breakdown of amino acids or in the bodys ability to get amino acids into cells. The molecule is a disaccharide composed of the monosaccharides glucose and fructose. Inherited metabolic disorders refer to different types of medical conditions caused by genetic defects most commonly inherited from both parents that interfere with the bodys metabolism. Approach to inborn errors of metabolism introduction.
Metabolism is the chemical process your body uses to transform the food you eat into the fuel that keeps you alive. Levels of trace metals in the blood are controlled by special proteins. Inborn errors of metabolism are defects in the mechanisms of the body which break down specific. Inborn errors of metabolism should always be considered in the differential diagnosis. Protein metabolism is the process to breakdown foods are used by the body to gain energy. In most disorders of metabolism, this can only be done with a synthetic formula which does not contain the toxic amino acid. Hendersonhasselbach equation measures the anion gap. Disorders affecting protein metabolism apollo international clinical.
In addition to their role as building blocks of protein, amino acids are key energy. Disorders of protein metabolism linkedin slideshare. Many sections cover a range of conditions that are managed in. Pyruvate dehydrogenase is the enzyme that converts pyruvate into acetyl coa, the molecule necessary to begin the krebs cycle to produce atp. The handout this handout is divided into several parts. Protein metabolism denotes the various biochemical processes responsible for the synthesis of proteins and amino acids anabolism, and the breakdown of proteins by catabolism. Disorders of monosaccharide metabolism include defects in transport glucosegalactose malabsorption, enzymes of galactose metabolism galactokinase, galactose1phosphate uridyl transferase, and. Walters published as a supplement to the journal ofclinical pathology bythe british medicalassociation, tavistock square, londonwc1h9jr. Nutrition food consists of proteins, carbohydrates, and fats. A brief summary of normal lipoprotein metabolism will be presented in this section and followed by a description of the impact. Explain how the urea cycle prevents toxic concentrations of nitrogen.
It has been called the epitome of human biochemical genetics. Nutrients follow a complex pathway from ingestion through anabolism and catabolism to energy production. Maple syrup urine disease msud phenylketonuria pku. A number of historical summaries are published on this disorder 8,9. Pyruvate dehydrogenase is the enzyme that converts pyruvate into acetyl coa, the. Metabolic disorders an overview sciencedirect topics. Its a hereditary disorder of tryptophan metabolism characterized by low plasma levels of tryptophan and their elevated urinary excretion. Pyruvate dehydrogenase complex deficiency and phenylketonuria pyruvate dehydrogenase complex deficiency pdcd and phenylketonuria pku are genetic disorders.
Metabolism is the process your body uses to get or make energy from the food you eat. Replacement therapy correction of underlying cause if possiblecorrection of underlying cause if possible iron. During transcription, rna polymerase transcribes a coding. Normally, the urea is transferred into the urine and removed from the body. The metabolism of the carbohydrates galactose, fructose, and glucose is intricately linked through interactions between different enzymatic pathways, and disorders that affect these pathways may have symptoms ranging from mild to severe or even lifethreatening. Most are rare but some are common, for example phenylketonuria pku occurs 1 in 12,000 births 1. Protein metabolism denotes the various biochemical processes responsible for the synthesis of proteins and amino acids anabolism, and the breakdown of proteins by catabolism the steps of protein synthesis include transcription, translation, and post translational modifications.
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