Expert consensus on screening, diagnosis and treatment of multiple carboxylase deficiency

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2022 Feb 25;51(1):129-135. doi: 10.3724/zdxbyxb-2022-0164.


Multiple carboxylase deficiency (MCD) includes autosomal recessive holocarboxylase synthetase (HLCS) deficiency and biotinidase (BTD) deficiency, which are caused by and gene mutations respectively. Neonatal screening for HLCS deficiency is based on 3-hydroxyisovaleryl carnitine in dry blood filter paper, and BTD deficiency is based on BTD activity determination. HLCS deficiency and BTD deficiency are characterized by neurocutaneous syndrome and organic aciduria, however, they are different in onset age, neurological symptoms and metabolic decompensation, which needed to be differentiated from acquired biotin deficiency or other genetic metabolic diseases. The diagnosis of the disease requires a combination of biochemical characteristics of hematuria, enzyme activity determination and genetic test. Routine biotin doses are effective for most MCD patients. This consensus is intended to benefit early screening and diagnosis of MCD.

Keywords: Biotinidase deficiency; Diagnosis and treatment; Expert consensus; Holocarboxylase synthetase deficiency; Multiple carboxylase deficiency; Neonatal screening.

MeSH terms

  • Biotin / metabolism
  • Biotin / therapeutic use
  • Biotinidase Deficiency* / drug therapy
  • Biotinidase Deficiency* / therapy
  • Carbon-Nitrogen Ligases* / genetics
  • Carbon-Nitrogen Ligases* / metabolism
  • Consensus
  • Holocarboxylase Synthetase Deficiency* / drug therapy
  • Holocarboxylase Synthetase Deficiency* / genetics
  • Humans
  • Infant, Newborn
  • Multiple Carboxylase Deficiency* / drug therapy
  • Neonatal Screening


  • Biotin
  • Carbon-Nitrogen Ligases

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