The term inborn errors of metabolism iem was first described by sir archibald garrod in 1908 to describe those diseases caused by a block in a metabolic pathway due to the deficient activity of a specific enzyme. Diagnosis is important not only for treatment but also for genetic counselling. Inborn errors of metabolism are rare genetic inherited disorders in which the body cannot properly turn food into energy. 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. May 17, 2008 inborn errors of metabolism iem are an important cause of acute illness in newborns. Affected patients may have failure to thrive, neurologic symptoms, digestive problems, psychomotor retardation, and a wide spectrum of laboratory findings. Dec 03, 2015 inborn errors of metabolism iems comprise a group of disorders in which a single gene defect causes a clinically significant block in a metabolic pathway resulting in either accumulation of substrate behind the block or deficiency of the product. Inborn errors of metabolism iems are a relatively infrequent cause of epilepsy, but their recognition is of paramount importance because many of these conditions are treatable, particularly those presenting in the neonatal period and in early infancy. 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 clinical presentation. Anesthetic management of patients with inborn errors of. Detection of inborn errors of metabolism in the newborn adc fetal. Inborn errors of metabolism are individually rare, but collectively numerous. Clinical approach to inborn errors of metabolism in. Sharma s1, kumar p, agarwal r, kabra m, deorari ak, paul vk.
However, their incidence may well be underestimated as diagnostic errors are frequent. 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. Most are rare but some are common, for example phenylketonuria pku occurs 1 in 12,000 births 1. Common metabolic disorder inborn errors of metabolism. The approach to diagnosis varies with the nature of severity of symptoms. Clinical approach to a newborn infant with suspected.
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. Appreciate that although most classic metabolic disorders present in infancy, most conditions can also present with milder variants later in life. The major classes of inborn errors of metabolism iem and their characteristic clinical and biochemical features are described below. Jan 01, 2002 inborn errors of metabolism iem often present as acute episodes that require hospital attention and emergency care. Approach to management of inborn errors of metabolism. Inborn errors of metabolism can induce disease manifestations in any organ at various stages of life, from newborn to adulthood. This makes it essential that the practicing pediatrician be familiar with the clinical presentation of these disorders. Inborn errors of metabolism causing epilepsy rahman. Inborn errors of metabolism should be considered in all patients with. Diagnosis is important not only for treatment but also for genetic. Neonatal presentations of inborn errors of metabolism. Inborn errors of metabolism american academy of pediatrics. How to recognize and treat inborn errors of metabolism presenting with neonatal liver disease carlo dionisivici, rome.
Inborn errors of metabolism 156 infancy, not with a specific laboratory abnormality, but with organomegaly, facial coarseness and neurodegeneration and show a progressively degenerative course. The clinical suspicion of an iem is essential, since the collection of appropriate laboratory samples during an episode of clinical decompensation is the key to a specific diagnosis. Inborn errors of metabolism are hereditary disorders in which gene defects cause clinically significant blocks in metabolic pathways. Inherited metabolic disorders symptoms and causes mayo clinic. Inborn errors of metabolism iem are individually rare, but collectively numerous. Inborn errors of metabolism iem can present as acute metabolic emergencies resulting in significant morbidity, progressive neurologic injury, or death. Approach to inborn error of metabolism in a neonate. Hyperammonemia is observed in a number of inborn errors of metabolism, including urea cycle defects, organic acidemias, and disorders of fattyacid oxidation 1. Inborn errors of metabolism stritch school of medicine. A practical clinical approach to the recognition of inborn errors of metabolism in the young infant is presented in.
As a whole, they can not be recognized through systematic neonatal screening tests, which are too slow, too expensive, or unreliable. Benign familial neonatal seizures bfns have onset on day 2 or 3 of life in 80% and presents with asymmetric tonic or oculofacial seizures. Clinical approach to inherited metabolic disorders in. Sep 20, 2017 inborn errors of metabolism iems individually are rare but collectively are common. Neonatology for the generalist clinical approach to. 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. Clinical symptoms are caused by deficiency of the pathway product andor toxicity resulting from the accumulation of an intermediary. Myoclonic or generalised seizures or epileptic spasms are not seen in this syndrome and neurological examination is normal.
Inborn errors of metabolism iem are an important cause of acute illness in newborns. Acute symptoms in the neonatal period and early infancy. Nov 29, 2011 approach to inborn errors of metabolism dr. Inborn errors of metabolism iems individually are rare but collectively are common. Texts on inborn errors of metabolism iems have traditionally focused on classical biochemistry, clinical presentation, and standard treatment approaches. 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 or impaired organelle function presenting as complicated. Inborn errors of metabolism iem are sometimes referred to as silent killers because they can strike healthyappearing fullterm infants without warning. This occurs when there is an increased production of fixed or nonvolatile acids with a. Adolescent presentations of inborn errors of metabolism. Trahms, in nutrition in the prevention and treatment of disease, 2001. Discuss methods for early recognition and treatment of neonates with inborn errors of metabolism 3. Inborn errors of metabolism ucsf benioff childrens hospital. In recent years, advancement in technologies such as tandem mass spectrometry msms and nextgeneration sequencing ngs.
The term inborn errors of metabolism was coined by a british physician, archibald garrod 18571936, in 1908. This topic provides an overview of the presentation, initial evaluation, and. Usually they are inherited as autosomal recessive disorders. Discuss advances in neonatal care of patients with inborn errors of metabolism. This approach will identify those infants who will benefit from additional evaluation and specific treatment. Ppt inborn errors of metabolism powerpoint presentation. Approach to inborn errors of metabolism presenting in the neonate suvasini sharma, pradeep kumar, ramesh agarwal, madhulika kabra, ashok deorari, vinod paul department of pediatrics all india institute of medical sciences ansari nagar, new delhi 110029 address for correspondence dr ashok k deorari professor department of pediatrics.
The incidence of iem ranges from 1 in 500 to 1 in 1500 births 1, 3, 46. Laboratory diagnostic approaches in metabolic disorders. The first opportunity to detect iem occurs during preconception counseling, when pregnant women. Neonatal hypoglycemia and inborn errors of metabolism rene santer, hamburg. It is important for paediatricians and neonatologists to keep in mind inborn errors of metabolism iems as a cause of illness in the neonatal period, as many disorders are treatable and, in most cases, successful outcome is dependent on a rapid diagnosis and early instigation of therapy. Metabolic emergencies in suspected inborn errors of metabolism. Clinical approach to inborn errors of metabolism presenting. He is known for work that prefigured the one geneone enzyme hypothesis, based on his studies on the nature and inheritance of alkaptonuria.
Detection of inborn errors of metabolism in the newborn. Clinical approach to inherited metabolic disorders. The disorders are usually caused by defects in specific proteins enzymes that help break down metabolize parts of food. Inborn errors of metabolism iem can present as acute metabolic.
Pdf inborn errors of metabolism iem are an important cause of acute illness in newborns. Inborn errors of amino acid metabolism can present at any time in a persons life. The report of an abnormal newborn screening test before symptoms have had a chance to develop is the most desirable for both the parents and the clinician. Fetal development for neonates with inborn errors of metabolism may have been normal, provided that the metabolites are able to cross the placenta and may be metabolized by the mother for the fetus. Inborn errors of metabolism are rare causes of seizures in the newborn. Presentation may mimic common neonatal conditions such as sepsis. Jan 01, 2019 inborn errors of metabolism iem, although individually rare, occur in 1 out of every 1,500 births. The pathogenetic mechanism is based on defects in a variety of cellular enzymes. Inborn errors of metabolism is the property of its rightful owner.
In order to make iem as easy and clear as possible, metabolic disorders presenting in the neonatal. Prompt detection requires a high index of suspicion and the early measurement of biochemical markers such as blood ammonia. 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 clinical presentation, and unfamiliarity with diagnostic tests. Approach to inborn errors of metabolism presenting in the neonate. Inborn errors of metabolism presenting in adolescence often are missed because of their low prevalence and high clinical variability. V metabolism metabolism catabolism breaking down anabolism building up enzymes play an important role in facilitating the process by serving as catalysts in the conversion of one chemical metabolite to another. Approach to inborn errors of metabolism presenting in the neonate article pdf available in the indian journal of pediatrics 753. Inborn errors of metabolism is an expansion on this model, one that establishes an innovative pathway approach and provides a new authority on this family of disease. Inborn errors of metabolism are individually rare, but collectively are responsible for significant levels of paediatric morbidity and mortality. Review differential for metabolic encephalopathy in the newborn.
Newborn screening also is contributing to the increased awareness of inherited metabolic disorders. Describe inborn errors of metabolism in neonates 2. Introduction to iem differential diagnosis of any sick neonate iem are individually rare overall incidence upto 1. Ethics in neonatology and inborn errors of metabolism. Inborn errors of metabolism iem are individually rare, but collectively.
Early detection and appropriate investigations prevent complications and save lives. Clinical approach to inborn errors of metabolism presenting in the newborn period. Inborn errors of metabolism iem constitute a group of inherited disorders that cause significant neonatal morbidity and mortality. Inborn errors of metabolism make up a large group of rare disorders caused by an inherited deficiency or absence of proteins that have enzymatic, carrier, receptor, or structural roles. The concept of inborn errors of metabolism iem was introduced by archibald garrod in 1909. In addition to impairment of energy generation, accumulation of substrates may occur, which can deposit in tissue and lead to organ dysfunction. Identifying redflag signs and symptoms of inborn errors is an essential skill for clinicians who care for adolescent and young adult patients with complex, atypical, or puzzling undiagnosed conditions. The number of diseases in humans known to be attributable to inherited point defects in metabolism now. Often therefore the neonate may be asymptomatic, and may only become symptomatic after the initiation of feeds or with intercurrent illness long periods of fasting. Even with untreatable disorders, it is important to establish the diagnosis in the index case in order to. Inborn errors of metabolism an inherited enzyme deficiency leading to the disruption of normal bodily metabolism accumulation of a toxic substrate compound acted. A practical clinical approach to the recognition of inborn errors of.
Develop a basic framework for understanding inborn errors of metabolism to aid in recognition and diagnosis of these conditions. Initial assessment of infants and children with suspected inborn errors of metabolism. Acute events in infancy including brief resolved unexplained event brue acute liver failure in children. Detection of inborn errors of metabolism in the newborn a chakrapani, m a cleary, j e wraith it is important for paediatricians and neonatologists to keep in mind inborn errors of metabolism iems as a cause of illness in the neonatal period, as many disorders are. Certain inborn errors of metabolism including galactosemia during the newborn period and certain organic acidopathies may be associated with. His seminal text, inborn errors of metabolism was published in 1923. 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. Inborn errors of metabolism in infancy and early childhood. Fetal development for neonates with inborn errors of metabolism may have been normal, provided that the metabolites are able to. Approach to inborn errors of metabolism learn pediatrics. 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. Children with inborn errors of metabolism can present to the clinician in a variety of ways. 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.
My this presentation describes how to approach a newborn infant with suspected inborn error of metabolism. Inborn errors of metabolism can present with multitude of signs and symptoms. Approach to inborn errors of metabolism presenting in the. 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 must be considered in the differential diagnosis of critically ill neonates and infants with severe hypoglycaemia, encephalopathy, acidaemia, conjugated hyperbilirubinaemia or hyperammonaemia for which there is no apparent cause after a conventional workup. The signs, when present, can be subtle, difficult to detect, or easy to mistake for other, more common neonatal pathologies. Recognition and diagnostic approach to acute metabolic. If an autopsy is not permitted, request consent for premortem or immediately post.
Clinical approach to inherited metabolic disorders in neonates. Types of inborn errors of metabolism laboratory findings inborn errors of metabolism laboratory evaluation for inborn errors of metabolism. Detection of inborn errors of metabolism in the newborn adc. However, they are an important cause of intractable neonatal seizures, accounting for 30% of cases. More than 400 biochemically diverse inborn errors of metabolism have been identified. Recognition and diagnostic approach to acute metabolic disorders. Presentation is usually in the neonatal period or infancy but can occur at any time, even in adulthood.
Metabolic disorders occurs more frequently in consanguineous marriages and can present anywhere from birth to adolescent period to adulthood depending on the type of metabolic defect and the penetrance. These conditions may also be called inborn errors of metabolism. Inborn errors of metabolism iem, although individually rare, occur in 1 out of every 1,500 births. May 27, 2014 approach to inborn errors of metabolism in neonates 1. Inborn errors of metabolism iem are characterized by the bodys inability to convert food into energy. Inborn error of metabolism an overview sciencedirect topics. The application of tandem mass spectrometry tandem ms to newborn screening and prenatal diagnosis has enabled. A free powerpoint ppt presentation displayed as a flash slide show on id. 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. 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. Approach to inborn errors of metabolism approach to inborn errors of metabolism andrew m. 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. Clinical approach to the diagnoses of inborn errors of metabolism. Neonatology for the generalist clinical approach to inborn.
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