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Multiple carboxylase deficiency

MedGen UID:
10119
•Concept ID:
C0026755
•
Disease or Syndrome
Synonym: Biotin-Responsive Multiple Carboxylase Deficiencies
SNOMED CT: Multiple carboxylase deficiency (1172966001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Related genes: HLCS, BTD
 
Monarch Initiative: MONDO:0015454
Orphanet: ORPHA148

Definition

A group of inborn errors of biotin metabolism characterised by reduced activities of biotin-dependent enzymes resulting in a wide spectrum of symptoms, including feeding difficulty, breathing difficulties, lethargy, seizures, skin rash, alopecia, and developmental delay. This group includes biotinidase deficiency and biotin holocarboxylase synthetase deficiency. [from SNOMEDCT_US]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Multiple carboxylase deficiency in Orphanet.

Professional guidelines

PubMed

Expert consensus on screening, diagnosis and treatment of multiple carboxylase deficiency.
Division of Biochemistry and Metabolism, Medical Genetics Branch, Chinese Medical Association, Division of Genetics and Metabolism, Child Diseases and Health Care Branch, Chinese Association for Maternal and Child Health, Division of Genetics and Metabolism, Rare Diseases Committee of Beijing Medical Association
Zhejiang Da Xue Xue Bao Yi Xue Ban 2022 Feb 25;51(1):129-135. doi: 10.3724/zdxbyxb-2022-0164. PMID: 35576117Free PMC Article
An Economic Evaluation of Neonatal Screening for Inborn Errors of Metabolism Using Tandem Mass Spectrometry in Thailand.
Thiboonboon K, Leelahavarong P, Wattanasirichaigoon D, Vatanavicharn N, Wasant P, Shotelersuk V, Pangkanon S, Kuptanon C, Chaisomchit S, Teerawattananon Y
PLoS One 2015;10(8):e0134782. Epub 2015 Aug 10 doi: 10.1371/journal.pone.0134782. PMID: 26258410Free PMC Article
Mutational analysis for biotinidase deficiency of a Greek patients' cohort ascertained through expanded newborn screening.
Thodi G, Molou E, Georgiou V, Loukas YL, Dotsikas Y, Biti S, Papadopoulos K, Konstantinou D, Antoniadi M, Doulgerakis E
J Hum Genet 2011 Dec;56(12):861-5. Epub 2011 Oct 20 doi: 10.1038/jhg.2011.119. PMID: 22011816

Curated

American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Elevated C5-OH Acylcarnitine, Organic Acidemias, 2022

American College of Medical Genetics and Genomics, Algorithm, Organic Acidemias: Elevated C5-OH, 2022

Recent clinical studies

Etiology

Inherited metabolic diseases mimicking hereditary spastic paraplegia (HSP): a chance for treatment.
Teive HAG, Camargo CHF, Pereira ER, Coutinho L, Munhoz RP
Neurogenetics 2022 Jul;23(3):167-177. Epub 2022 Apr 9 doi: 10.1007/s10048-022-00688-3. PMID: 35397036
Genetic mimics of cerebral palsy.
Pearson TS, Pons R, Ghaoui R, Sue CM
Mov Disord 2019 May;34(5):625-636. Epub 2019 Mar 26 doi: 10.1002/mds.27655. PMID: 30913345
Biotin in metabolism, gene expression, and human disease.
León-Del-Río A
J Inherit Metab Dis 2019 Jul;42(4):647-654. Epub 2019 Mar 19 doi: 10.1002/jimd.12073. PMID: 30746739
Biochemical signatures mimicking multiple carboxylase deficiency in children with mutations in MT-ATP6.
Larson AA, Balasubramaniam S, Christodoulou J, Burrage LC, Marom R, Graham BH, Diaz GA, Glamuzina E, Hauser N, Heese B, Horvath G, Mattman A, van Karnebeek C, Lane Rutledge S, Williamson A, Estrella L, Van Hove JKL, Weisfeld-Adams JD
Mitochondrion 2019 Jan;44:58-64. Epub 2018 Jan 4 doi: 10.1016/j.mito.2018.01.001. PMID: 29307858Free PMC Article
Fetal drug therapy.
Evans MI, Pryde PG, Reichler A, Bardicef M, Johnson MP
West J Med 1993 Sep;159(3):325-32. PMID: 8236974Free PMC Article

Diagnosis

Biotin-responsive Multiple Carboxylase Deficiency (MCD).
Majid H, Ahmed S, Muneer S, Hamid R, Jafri L, Khan AH
J Coll Physicians Surg Pak 2022 Jun;32(6):823-825. doi: 10.29271/jcpsp.2022.06.823. PMID: 35686422
Expert consensus on screening, diagnosis and treatment of multiple carboxylase deficiency.
Division of Biochemistry and Metabolism, Medical Genetics Branch, Chinese Medical Association, Division of Genetics and Metabolism, Child Diseases and Health Care Branch, Chinese Association for Maternal and Child Health, Division of Genetics and Metabolism, Rare Diseases Committee of Beijing Medical Association
Zhejiang Da Xue Xue Bao Yi Xue Ban 2022 Feb 25;51(1):129-135. doi: 10.3724/zdxbyxb-2022-0164. PMID: 35576117Free PMC Article
Inherited metabolic diseases mimicking hereditary spastic paraplegia (HSP): a chance for treatment.
Teive HAG, Camargo CHF, Pereira ER, Coutinho L, Munhoz RP
Neurogenetics 2022 Jul;23(3):167-177. Epub 2022 Apr 9 doi: 10.1007/s10048-022-00688-3. PMID: 35397036
Genetic mimics of cerebral palsy.
Pearson TS, Pons R, Ghaoui R, Sue CM
Mov Disord 2019 May;34(5):625-636. Epub 2019 Mar 26 doi: 10.1002/mds.27655. PMID: 30913345
Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism.
Baumgartner ER, Suormala T
Int J Vitam Nutr Res 1997;67(5):377-84. PMID: 9350481

Therapy

Biotin-responsive Multiple Carboxylase Deficiency (MCD).
Majid H, Ahmed S, Muneer S, Hamid R, Jafri L, Khan AH
J Coll Physicians Surg Pak 2022 Jun;32(6):823-825. doi: 10.29271/jcpsp.2022.06.823. PMID: 35686422
Expert consensus on screening, diagnosis and treatment of multiple carboxylase deficiency.
Division of Biochemistry and Metabolism, Medical Genetics Branch, Chinese Medical Association, Division of Genetics and Metabolism, Child Diseases and Health Care Branch, Chinese Association for Maternal and Child Health, Division of Genetics and Metabolism, Rare Diseases Committee of Beijing Medical Association
Zhejiang Da Xue Xue Bao Yi Xue Ban 2022 Feb 25;51(1):129-135. doi: 10.3724/zdxbyxb-2022-0164. PMID: 35576117Free PMC Article
Vitamin-responsive disorders: cobalamin, folate, biotin, vitamins B1 and E.
Baumgartner MR
Handb Clin Neurol 2013;113:1799-810. doi: 10.1016/B978-0-444-59565-2.00049-6. PMID: 23622402
Biotin.
Altern Med Rev 2007 Mar;12(1):73-8. PMID: 17397270
Two forms of biotin-responsive multiple carboxylase deficiency.
Sweetman L
J Inherit Metab Dis 1981;4(2):53-4. doi: 10.1007/BF02263587. PMID: 6790844

Prognosis

Case report of holocarboxylase synthetase deficiency (late-onset) in 2 Chinese patients.
Xiong Z, Zhang G, Luo X, Zhang N, Zheng J
Medicine (Baltimore) 2020 May;99(18):e19964. doi: 10.1097/MD.0000000000019964. PMID: 32358368Free PMC Article
Genetic mimics of cerebral palsy.
Pearson TS, Pons R, Ghaoui R, Sue CM
Mov Disord 2019 May;34(5):625-636. Epub 2019 Mar 26 doi: 10.1002/mds.27655. PMID: 30913345
Inherited metabolic diseases in the Southern Chinese population: spectrum of diseases and estimated incidence from recurrent mutations.
Hui J, Tang NL, Li CK, Law LK, To KF, Yau P, Fung SL, Chong JS, Tsung L, Chiang G, Fung E, Cheung KL, Yeung WL, Fok TF
Pathology 2014 Aug;46(5):375-82. doi: 10.1097/PAT.0000000000000140. PMID: 24992243
Reduced half-life of holocarboxylase synthetase from patients with severe multiple carboxylase deficiency.
Bailey LM, Ivanov RA, Jitrapakdee S, Wilson CJ, Wallace JC, Polyak SW
Hum Mutat 2008 Jun;29(6):E47-57. doi: 10.1002/humu.20766. PMID: 18429047
Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism.
Baumgartner ER, Suormala T
Int J Vitam Nutr Res 1997;67(5):377-84. PMID: 9350481

Clinical prediction guides

Biotin-responsive Multiple Carboxylase Deficiency (MCD).
Majid H, Ahmed S, Muneer S, Hamid R, Jafri L, Khan AH
J Coll Physicians Surg Pak 2022 Jun;32(6):823-825. doi: 10.29271/jcpsp.2022.06.823. PMID: 35686422
Holocarboxylase synthetase knockout is embryonic lethal in mice.
Sadri M, Wang H, Kuroishi T, Li Y, Zempleni J
PLoS One 2022;17(4):e0265539. Epub 2022 Apr 6 doi: 10.1371/journal.pone.0265539. PMID: 35385533Free PMC Article
Selective Screening for Organic Acidurias and Amino Acidopathies in Pakistani Children.
Sherazi NA, Khan AH, Jafri L, Jamil A, Khan NA, Afroze B
J Coll Physicians Surg Pak 2017 Apr;27(4):218-221. PMID: 28492150
Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism.
Baumgartner ER, Suormala T
Int J Vitam Nutr Res 1997;67(5):377-84. PMID: 9350481
Biotinidase deficiency: initial clinical features and rapid diagnosis.
Wolf B, Heard GS, Weissbecker KA, McVoy JR, Grier RE, Leshner RT
Ann Neurol 1985 Nov;18(5):614-7. doi: 10.1002/ana.410180517. PMID: 4073853

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG ACT, 2022
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Elevated C5-OH Acylcarnitine, Organic Acidemias, 2022
    • ACMG Algorithm, 2022
      American College of Medical Genetics and Genomics, Algorithm, Organic Acidemias: Elevated C5-OH, 2022

    Reviews

    Related information

    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • MeSH
      Related Medical Subject Headings
    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed

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