GTR Home > Conditions/Phenotypes > Holocarboxylase synthetase deficiency


Early-onset multiple carboxylase deficiency, or holocarboxylase deficiency, is an autosomal recessive disorder of biotin metabolism. See also late-onset or juvenile MCD (253260) caused by mutation in the biotinidase gene (BTD; 609019). Sweetman (1981) recognized that multiple carboxylase deficiency could be classified into early and late forms. The early form showed higher urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxypropionic acid than the late form and was associated with normal plasma biotin concentrations. Sweetman (1981) proposed a defect in holocarboxylase synthetase and intestinal biotin absorption, respectively. Care must be taken to differentiate the inherited multiple carboxylase deficiencies from acquired biotin deficiencies, such as those that develop after excessive dietary intake of avidin, an egg-white glycoprotein that binds specifically and essentially irreversibly to biotin (Sweetman et al., 1981) or prolonged parenteral alimentation without supplemental biotin (Mock et al., 1981). [from OMIM]

Available tests

42 tests are in the database for this condition. Compare labs offering these tests.

Check Associated genes and Related conditions for additional relevant tests.

Associated genes

  • Also known as: HCS, HLCS
    Summary: holocarboxylase synthetase (biotin-(proprionyl-CoA-carboxylase (ATP-hydrolysing)) ligase)

Clinical features

  • Alopecia
  • Hyperventilation
  • Irritability
  • Thrombocytopenia
  • Hypertonia
  • Respiratory insufficiency
  • Abnormal pattern of respiration
  • Incoordination
  • Seizure
  • Cheilitis
  • Dry skin
  • Feeding difficulties in infancy
  • Vomiting
  • Behavioral abnormality
  • Skin rash
  • Muscular hypotonia
  • Lethargy
  • Coma
  • Global developmental delay
  • Weight loss
  • Metabolic acidosis
  • Hyperammonemia
  • Organic aciduria
  • Nausea and vomiting
  • Tachypnea
  • Reduced consciousness/confusion
  • Inflammatory abnormality of the eye
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