Holocarboxylase Synthetase Deficiency Workup

Updated: Apr 17, 2018
  • Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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Laboratory Studies

Initial studies in holocarboxylase synthetase (HCS) deficiency should include the following:

  • Serum electrolyte levels

  • Blood ammonia levels

  • Urinalysis

  • Culture samples appropriate for an evaluation for Sepsis

Aside from demonstration of an anion gap, hyperammonemia, and systemic acidosis, no routine laboratory tests are of use; in this context, urinary odor, if present, may be of critical importance in making a rapid diagnosis.

Urinary organic acid evaluation demonstrates the presence of lactate, beta-hydroxypropionate, beta-methylcrotonate, and beta-hydroxyisovalerate, as well as numerous other quantitatively less apparent organic acids.

Making a definitive biochemical diagnosis depends on demonstration of impaired activity of pyruvate, propionyl-CoA, and beta-methylcrotonyl-CoA carboxylases in white cells or cultured fibroblasts.

Techniques for direct sequencing of holocarboxylase synthetase gene mutations are available and should be performed following definitive diagnosis.

Prenatal diagnosis using chorionic villus biopsy samples and direct sequencing of fetal DNA has been reported. [14]