The Future Pathophysiology Inborn errors of metabolism (IEMs) 


The Future Pathophysiology Inborn errors of metabolism (IEMs) 
Inborn errors of metabolism (IEMs) individually are rare but collectively are common. Presentation is usually in the neonatal period or infancy but can occur at any time, even in adulthood. Diagnosis does not require extensive knowledge of biochemical pathways or individual metabolic diseases. An understanding of the major clinical manifestations of inborn errors of metabolism provides the basis for knowing when to consider the diagnosis. A high index of suspicion is most important in making the diagnosis.
Inborn errors of metabolism (IEMs) individually are rare but collectively are common. Presentation is usually in the neonatal period or infancy but can occur at any time, even in adulthood. Diagnosis does not require extensive knowledge of biochemical pathways or individual metabolic diseases. An understanding of the major clinical manifestations of inborn errors of metabolism provides the basis for knowing when to consider the diagnosis. A high index of suspicion is most important in making the diagnosis. Asymptomatic neonates with newborn screening results positive for an inborn error of metabolism may require emergent evaluation including confirmatory testing, and as appropriate, initiation of disease-specific management.

The Future Pathophysiology

Single gene defects result in abnormalities in the synthesis or catabolism of proteins, carbohydrates, fats, or complex molecules. Most are due to a defect in an enzyme or transport protein, which results in a block in a metabolic pathway. Effects are due to toxic accumulations of substrates before the block, intermediates from alternative metabolic pathways, defects in energy production and use caused by a deficiency of products beyond the block, or a combination of these metabolic deviations. Nearly every metabolic disease has several forms that vary in age of onset, clinical severity, and, often, mode of inheritance.

Categories of inborn errors of metabolism, or IEMs, are as follows:

  • Disorders that result in toxic accumulation
  • Disorders of protein metabolism (eg, amino acidopathies, organic acidopathies, urea cycle defects)
  • Disorders of carbohydrate intolerance
  • Lysosomal storage disorders

Disorders of energy production, utilization

  • Fatty acid oxidation defects
  • Disorders of carbohydrate utilization, production (ie, glycogen storage disorders, disorders of gluconeogenesis and glycogenolysis)
  • Mitochondrial disorders
  • Peroxisomal disorders
Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s