304 North Cardinal St.
Dorchester Center, MA 02124
Inborn errors of metabolism (IEMs) are a group of rare genetic disorders that affect the body’s metabolic processes leading to a wide range of symptoms and clinical manifestations.
Inborn metabolic disorders are caused by genetic mutations that affect enzymes, transporters, or other proteins involved in biochemical pathways. These mutations leads to either accumulation or deficiency of certain metabolites. These conditions can manifest in infancy, childhood, or adulthood and can cause serious consequences if left untreated.
The concept of IEMs emerged in the early 1900s when researchers began to link certain clinical symptoms with abnormal metabolic profiles.
In 1908, the British physician Archibald Garrod proposed that some diseases might be caused by a genetic defect in the production or metabolism of certain proteins. Garrod’s idea was based on observations of patients with alkaptonuria, a rare disorder characterized by dark urine due to the accumulation of homogentisic acid.
Garrod suggested that alkaptonuria was caused by a deficiency of an enzyme that normally breaks down homogentisic acid. He also noted that the condition was inherited in an autosomal recessive pattern, which suggested a genetic basis. Garrod’s work was revolutionary as it established a link between genetics and biochemistry and paved the way for the study of inborn errors of metabolism.
Since then, researchers have identified hundreds of these metabolic diseases. Each of the diseases are characterized by a specific metabolic defect.
These disorders can affect a wide range of metabolic pathways, including carbohydrate, lipid, amino acid, and organic acid metabolism. Some common examples include phenylketonuria (PKU), galactosemia, and glycogen storage disease.
The identification of IEMs has been instrumental in advancing our understanding of the complex interplay between genetics and biochemistry. These disorders have served as a bridge between these two fields helping to elucidate the genetic basis of biochemical pathways and vice versa.
For example, the study of IEMs has led to the identification of many genes and proteins involved in metabolic pathways, as well as the development of new biochemical assays for their detection.
In addition, the study of inborn errors of metabolism has led to the development of new treatment approaches. These include dietary modifications, enzyme replacement therapy, and gene therapy. These therapies have revolutionized the care of patients along with improving their quality of life.
Despite these advances, it remains a major challenge for healthcare providers and researchers. These disorders are often difficult to diagnose as they can present with a wide range of symptoms and can mimic other conditions. Also, the treatment of inborn errors can be complex and requires a multidisciplinary approach involving specialists in genetics, biochemistry, and nutrition.