Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (421 page)

   Diagnostic molecular testing:

   Targeted mutation analysis ethnic specific: Ashkenazi individuals may be tested initially for the two, ABCC8 mutations: Phe1387del and c.3989-9G>A; Finnish individuals for the founder mutations in ABCC8: p. Val187Asp and p.Glu1506Lys.

   Sequence analysis: Comprehensive molecular genetic testing may focus on selected genes or on a multigene panel. Individuals with elevated serum ammonia should first be tested for mutations in GLUD1. Individuals with neonatal onset of severe disease should be tested for ABCC8 and KCNJ11 first.

   Carrier testing: Requires prior identification of the disease-causing mutations in the family

   Prenatal diagnosis and preimplantation genetic diagnosis (PGD): Requires prior identification of the disease-causing mutations in the family

   Other Considerations

In approximately 50% of cases, the genetic cause of hyperinsulinism is unknown.

Suggested Reading

Glaser B. Familial hyperinsulinism. In: Pagon RA, Adam MP, Bird TD, et al., eds.
GeneReviews
^™
[Internet]
. Seattle, WA: University of Washington, Seattle; 2003:1993–2013 [Updated 2013 Jan 24]. Available from:
http://www.ncbi.nlm.nih.gov/books/nbk1375/

MAPLE SYRUP URINE DISEASE (MSUD)

MIM #248600

   Definition

   Maple syrup urine disease (MSUD) is an inherited disorder in which the body is unable to process three amino acids: leucine, isoleucine, and valine. MSUD can be caused by homozygous or compound heterozygous mutation in at least three genes: BCKDHA (MSUD type 1A), BCKDHB (MSUD type 1B), and DBT (MSUD type 2). These genes encode two of the catalytic components of the branched-chain alpha-ketoacid dehydrogenase (BCKD), which catalyzes the metabolism of the branched-chain amino acids, leucine, isoleucine, and valine. People with MSUD have a defective BCKD protein complex resulting in buildup of toxic levels of these amino acids in the body.

   Who Should Be Suspected?

MSUD causes loss of appetite, fussiness, and sweet-smelling urine. The elevated levels of amino acids in the urine generate the smell, which is suggestive of maple syrup.

   Relevant Tests and Diagnostic Value

Biochemical testing:

   Quantitative plasma amino acid analysis.

   Tandem mass spectrometry (MS/MS)–based amino acid profiling. Newborn screening (NBS) programs that employ tandem mass spectrometry detect MSUD.