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Advances in inborn errors of metabolism

Inborn errors of metabolism are rare diseases caused by defects of single genes, which code for enzymes that facilitate the conversion of substrates into metabolites. These diseases often arise due to the accumulation of toxic substrates or a deficiency of essential metabolites. The management of inborn errors of metabolism has traditionally consisted in diet therapy and supportive therapy, but recently other treatment options have become available, including enzyme and coenzyme replacement, removal of harmful substances, cell and organ transplantation, and gene therapy. Inborn errors of metabolism are currently one of the hottest topics in medicine since patients with certain inherited metabolic…

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 Inborn errors of metabolism in the 21st century: past to present

The 21st century is an exciting time to be in the field of metabolic medicine. As with many fields, one of the keys to anticipating the future is to understand the past. The term “inborn error of metabolism” was first coined in 1908 by Sir Archibald Garrod, in reference to four disorders (alkaptonuria, pentosuria, cystinuria and albinism). The first (and still most definitive) textbook on the subject, “The Metabolic Basis of Inherited Disease” was initially published in 1960 and covered 80 disorders in 1,477 pages. After the eighth edition of this text became unwieldy at 6,338 pages in 4 volumes covering more than 1,000 disorders, the book was changed to an online reference text with 259 chapters and is still growing. Current newborn screening on a few dried blood spots on filter paper identifies more than 1 in 2,000 newborns as having a metabolic disorder. The availability of metabolomic and genomic analyses is resulting in the diagnosis of many new disorders. Enzyme replacement therapy (ERT) has provided treatments for previously untreatable metabolic disorders, and the promise of gene therapy on the near horizon will certainly revolutionize the field.

Articles of Interest

Causes of ADHD: Inherited Metabolic Disorders (IEMs)

There are many types of IEM diseases that cause abnormal brain nerve symptoms, and there are also many metabolic disorder pathways involved.

Common metabolic disorder (inborn errors of metabolism) concerns in primary care practice

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 medical conditions involving several human organ systems. They involve great complexity of the underlying pathophysiology, biochemical workup, and molecular analysis, and have complicated therapeutic options for management. Age of presentation can vary from infancy to adolescence with the more severe forms appearing in early childhood accompanied by significant morbidity and mortality.

Inborn Errors of Metabolism

Inborn errors of metabolism can be divided into four parts, based on the defect of a metabolic pathway. These separate parts include: (1) Ineffective or missing transport proteins or complexes that normally allow for passage of a needed substance across cell membranes, (2) Lack of catalyzing enzyme (s) for an essential pathway, (3) Blockage of a primary metabolic pathway, requiring the use of an alternative pathway and (4) Deficient cofactor for a metabolic pathway.

Inborn Errors of Metabolism (Metabolic Disorders)

Metabolic disorders can appear to be a frustratingly complex group of disorders to master. Many individual disorders have clinical presentations that initially seem very similar to one another. In addition, classification systems can be difficult to apply because of the multitude and variety of metabolic pathways involved.

Inborn Errors of Metabolism in Infancy and Early Childhood: An Update

The topic of inborn errors of metabolism is challenging for most physicians. The number of known metabolic disorders is probably as large as the number of presenting symptoms that may indicate metabolic disturbances. Furthermore, physicians know they may not encounter certain rare inborn errors of metabolism during a lifetime of practice. Nonetheless, with a collective incidence of one in 1,500 persons, at least one of these disorders will be encountered by almost all practicing physicians.

Inborn Errors of Metabolism- the Great Hepatic Masquerader

Diagnosis of inborn error of metabolism should be suspected if there are extrahepatic manifestations that cannot be explained solely by intrinsic hepatic dysfunction.

Inborn Errors of Metabolism: Becoming Ready for Rare

Inborn errors of metabolism (IEMs) are a large group of disorders that can present in any age group and must be considered in the differential diagnosis for a variety of signs and symptoms appearing in infants and children. The rarity and complexity of these conditions often make them difficult to recognize, as they may mimic more common conditions.

Inborn errors of metabolism: Definition and examples

IEMs are a group of conditions that disrupt a metabolic pathway. These disorders typically occur due to problems with specific enzymes that help to metabolize or store macronutrients, such as carbohydrates, fats, and proteins. Problems with these biochemical reactions can result in a buildup of toxic substances, which can have significant health complications.

Inborn Errors of Metabolism: From Neonatal Screening to Metabolic Pathways

The book ‘Inborn Errors of Metabolism: From Neonatal Screening to Metabolic Pathways’ edited by two well-known specialists in the area of inborn errors of metabolism (IEMs), Brendan Lee and Fernando Scaglia, gives us a different vision in this field. It was a pleasure to review this book, to be able to browse through it and appreciate it. This is not a common textbook, neither is it a regular book on IEMs. It is a ‘guide’ into the field of metabolic diseases; it is a comprehensive and updated history of a rapidly evolving field. This is an interesting and original work that will certainly be relevant for students as well as specialists.

Inborn Errors of Metabolism: From Preconception to Adulthood

Inborn errors of metabolism (IEM), although individually rare, occur in 1 out of every 1,500 births. The first opportunity to detect IEM occurs during preconception counseling, when pregnant women and couples considering future pregnancies can undergo carrier screening. For individuals of all ethnic backgrounds, the screening includes testing for a variety of IEM and non-IEM. For individuals of Ashkenazi Jewish descent, carrier screening, per the American College of Medical Genetics and Genomics, also includes testing for Tay-Sachs disease and four other IEM. Inborn errors of metabolism can present in utero; in newborns; or in children, adolescents, and adults.

Inborn Metabolics Deseases

Due the complexity of biological events, metabolic diseases present, in the majority of cases, with systemic symptoms, involving more organs and apparatuses. The involvement of the central nervous system is very frequent while the involvement of a single organ is rare. With reference to the mechanism of intoxication, it can be acute or chronic and slowly progressive.

Metabolic Disorders

Most metabolic disorders are caused by the genetic deficiency of an enzyme that is needed to convert one chemical into another. For example, phenylketonuria, or "PKU," is caused by a deficiency of the enzyme phenylalanine hydroxylase, which converts the dietary amino acid, phenylalanine, into another amino acid, tyrosine. The deficiency of phenylalanine hydroxylase leads to the accumulation of a toxic level of phenylalanine and a deficiency of tyrosine, both of which damage the developing brain and cause severe intellectual disabilities. Other adverse effects of metabolic diseases include seizures, movement disorders, poor growth, muscle weakness, fasting intolerance and disproportionate illness with simple childhood infections or immunizations.

The Basics of Inborn Errors of Metabolism

A clinical and diagnostic perspective...

Resources

IEMbase

Inborn errors of metabolism (IEMs) represent a large class of rare genetic disorders. For a considerable proportion of IEM, therapy is available, which dramatically improves patient outcomes. Accurate and timely diagnosis is therefore essential. However, the accuracy and timeliness of an IEM diagnosis is often difficult to achieve due to a staggering number of these rare genetic disorders, the heterogeneity of symptoms and phenotypes, as well as the extensive list of required tests and skills to properly interpret these in the context of the patient’s phenotype.

Society for Study of Inborn Errors of Metabolism

The aim of the Society is to foster the study of inherited metabolic disorders and related topics. The Society, founded in 1963, exists to promote exchange of ideas between professional workers in different disciplines who are interested in inherited metabolic disease.