Holocarboxylase Synthetase Deficiency Clinical Presentation

Updated: Apr 17, 2018
  • Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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As a water-soluble vitamin, biotin easily crosses the placenta; thus, the infant with holocarboxylase synthetase (HCS) deficiency in utero grows uneventfully.

Birth weight, Apgar scores, and initial physical examination findings are entirely normal.

Because of the autosomal recessive inheritance, a family history of the disorder is unlikely. [10]



The major clinical findings of holocarboxylase synthetase deficiency include severe ketoacidosis, exfoliative dermatitis, and hypoglycemia.

As in individuals with other organic acidemias, whether fed or fasted, the increased accumulation of ketoacids causes tachypnea, irritability, lethargy, vomiting, and, eventually, coma.

Exfoliative dermatitis is usually absent in the earliest stages of clinical presentation.

Observe for unusual odors in the urine.



Presentation must be distinguished from all other causes, such as other organic acidemias, sepsis, and galactosemia.

The gene locus has been mapped to band 21q22.1, with a limited number of allelic variants described. A particular allelic variant, the p.L216R mutation, results in an unstable protein with increased turnover and a clinical picture of relative biotin-resistance. [11] Treatment of these patients with massive amounts of daily biotin (>1 g) has resulted in relatively good outcomes. [12, 13]