Inborn Errors of Metabolism Differential Diagnoses

Updated: Sep 20, 2017
  • Author: Debra L Weiner, MD, PhD; Chief Editor: Robert P Hoffman, MD  more...
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Diagnostic Considerations

Consider IEMs in all neonates and young infants with unexplained death. Obtain specimens immediately postmortem in children with unexplained death.

A systematic literature review identified 89 IEMs presenting with intellectual developmental disorders (IDD) as prominent features and amenable to causal therapy. All 89 IEMs except one (tyrosinemia type II) were associated with at least one additional prominent neurologic feature (eg, epilepsy) and movement disorders (eg, spasticity, dyskinesia, and ataxia). However, many of these conditions can present with only IDD prior to manifestation of the full phenotype (eg, disorders of creatine synthesis and transport). Sixty percent of these IEMs can be diagnosed by metabolic blood and urine screening tests.  For the remaining disorders, specific tests are required for diagnosis, including primary molecular analysis.  A 2-tier algorithm has been developed to provide a structured approach to the diagnosis of treatable IEMs in patients presenting with an IDD of unknown etiology. [12]

IEMs constitute an important group of genetic causes of parkinsonism at any age but particularly in children with parkinsonism-like symptoms. IEMs known to cause parkinsonism are metal-storage diseases, neurotransmitter defects, lysosomal storage disorders, and energy metabolism defects. [3]

Differential Diagnoses