Inborn Errors of Metabolism
Biochemical pathways play an integral and essential part in the proper functioning of the human body. Defects in the production, breakdown or transport of a specific enzyme or protein can have deleterious consequences. Ultimately, disorders resulting from inborn errors of metabolism (IEM) are caused by the deficiency of a particular enzyme, and/or the accumulation of abnormal metabolites.
IEMs can be categorized as follows:
- Disorders of protein metabolism: Organic acidopathies, amino acidopathies, urea cycle defects
- Disorders of carbohydrate metabolism: Galactosemia, glycogen storage disorders
- Disorders of fatty acid oxidation: Medium-chain acyl CoA dehydrogenase (MCAD) deficiency
- Mitochondrial disorders
- Lysosomal disorders: Hurler syndrome, Hunter syndrome, Tay-Sachs
- Peroxisomal disorders: Zellweger syndrome, X-linked adrenoleukodystrophy (X-ALD)
Many inborn errors of metabolism will manifest symptoms in the newborn period, including the organic acidemias, the urea cycle defects, and certain disorders of amino acid metabolism.
Features suggestive of IEM in the newborn period include:
- Lethargy
- Vomiting
- Breathing problems - apnea or tachypnea
- Failure to thrive
- Jaundice
- Seizures
Common Screening Tests:
- Lactate/Pyruvate
- Ammonia
- Arterial blood gas
- Blood glucose
- Plasma amino acids
- Urine organic acids
- Urine ketones
- Plasma acyl-carnitine profile
The majority of IEM are inherited in an autosomal recessive manner; although there are a few that have X-linked recessive inheritance. Examples of IEMs with X-linked recessive inheritance:
- Ornithine transcarbamylase (OTC) deficiency - urea cycle defect
- Hunter syndrome - lysosomal storage disorder
- X-linked adrenoleukodystrophy (X-ALD) - peroxisomal disorder
Some of the more common IEMs are discussed below.
