Holocarboxylase synthetase deficiency usually causes earlier
and more severe disease than biotinidase deficiency, with life-threatening ketoacidosis;
alopecia; and a generalized red, scaly rash. Coma, apnea, and death
often follow unless therapy is instituted. Biotinidase deficiency
usually presents later in infancy with periorificial dermatitis
resembling acrodermatitis enteropathica; patchy alopecia; and neurological
abnormalities such as ataxia, neurosensory defects, developmental
delay, and convulsions. In both conditions, the rash may be complicated
by superinfection with monilia. The defect in neonatal disease is
usually in holocarboxylase synthetase; in most patients with a later
onset, the defect is in biotinidase. However, there is extensive
overlap between the two conditions, and accurate diagnosis can be
made only by enzyme assay.