Genetic metabolic diseases are congenital errors of the body’s chemistry that affect the way in which food is assimilated, energy generated, and tissue growth enabled. 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. Some metabolic diseases become manifest in the first few days of life, whereas others require a stress, such as a fever or fasting during an illness, to become manifest. The most severe metabolic diseases can be lethal if not treated immediately after birth, while others may cause only very slow injury or lead to a damaging metabolic crisis only once in a lifetime. Although each metabolic disease individually is rare, there are more than 1300 known metabolic diseases, and collectively they represent a significant cause of illness and disability in children. Although all state newborn screening programs test for metabolic diseases, most states test for fewer than 10 of the more common ones. Specialized laboratory testing available only in a few major pediatric centers, like Kennedy Krieger Institute, is required to diagnose most metabolic diseases.

Examples, Subsets and Synonyms for Metabolic Disorders (Inborn Errors of Metabolism)

• Disorders Amino Acid Metabolism (amino acidemias) -

• Maple Syrup Urine Disease (MSUD)
• Homocystinuria

• Disorders of Organic Acid Metabolism (organic acidurias, organic acidemias) -

• Methylmalonic Aciduria
• 3-Methylglutaconic Aciduria – Barth Syndrome
• Glutaric Aciduria
• 2-Hydroxyglutaric aciduria – D and L forms

• Disorders of Fatty Acid Beta-Oxidation -

• MCAD Deficiency
• LCHAD, VLCAD deficiency

• Disorders of Lipid Metabolism (lipid storage disorders) -

• Gangliosidoses -

• GM1 Gangliosidosis
• Tay-Sachs Disease
• Sandhoff Disease

• Sphingolipidoses -

• Fabry Disease
• Gaucher Disease
• Niemann-Pick Disease
• Krabbe Disease

• Mucolipidoses
• Mucopolysaccharidoses

• Mitochondrial Disorders -

Mitochondrial cardiomyopathies

Leigh disease

MELAS, MERRF, NARP

Barth syndrome

• Peroxisomal Disorders -

Zellweger Syndrome (cerebrohepatorenal syndrome)

X-Linked Adrenoleukodystrophy

Refsum Disease