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Pathway Description
Multiple Carboxylase Deficiency, Neonatal or Early Onset Form
Homo sapiens
Disease Pathway
Created: 2013-08-29
Last Updated: 2022-10-13
Holocarboxylase synthetase deficiency also called Multiple Carboxylase Deficiency, Neonatal or Early Onset Form, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of either mutations in the BTD gene or the HLCS gene. The BTD gene encodes for biotinidase and the HLCS gene encodes for holocarboxylase synthetase. This disorder is classified as a multiple carboxylase deficiency, a group of disorders characterized by impaired activity of enzymes dependent on biotin. Symptoms of holocarboxylase synthetase deficiency typically appear within the first few months of life, and include difficulty feeding, breathing problems, a skin rash, hair loss, and lethargy. Treatment using biotin supplements if immediate and lifelong can be effective in preventing many complications and managing the disorder. However, if left untreated the disorder can lead to delayed development, seizures, and coma.
References
Multiple Carboxylase Deficiency, Neonatal or Early Onset Form References
[Metagen: MULTIPLE CARBOXYLASE DEFICIENCY, NEONATAL OR EARLY ONSET FORM](http://metagene.de/program/d.prg?id_d=79)
[OMIM: 253270](http://omim.org/entry/253270})
[NIH](http://ghr.nlm.nih.gov/condition/holocarboxylase-synthetase-deficiency)
Baumgartner ER, Suormala T: Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism. Int J Vitam Nutr Res. 1997;67(5):377-84.
Pubmed: 9350481
Biotin Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Pacheco-Alvarez D, Solorzano-Vargas RS, Del Rio AL: Biotin in metabolism and its relationship to human disease. Arch Med Res. 2002 Sep-Oct;33(5):439-47.
Pubmed: 12459313
Suzuki Y, Yang X, Aoki Y, Kure S, Matsubara Y: Mutations in the holocarboxylase synthetase gene HLCS. Hum Mutat. 2005 Oct;26(4):285-90. doi: 10.1002/humu.20204.
Pubmed: 16134170
Suzuki Y, Aoki Y, Ishida Y, Chiba Y, Iwamatsu A, Kishino T, Niikawa N, Matsubara Y, Narisawa K: Isolation and characterization of mutations in the human holocarboxylase synthetase cDNA. Nat Genet. 1994 Oct;8(2):122-8. doi: 10.1038/ng1094-122.
Pubmed: 7842009
Ohira M, Seki N, Nagase T, Suzuki E, Nomura N, Ohara O, Hattori M, Sakaki Y, Eki T, Murakami Y, Saito T, Ichikawa H, Ohki M: Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21. Genome Res. 1997 Jan;7(1):47-58. doi: 10.1101/gr.7.1.47.
Pubmed: 9037601
Cole H, Reynolds TR, Lockyer JM, Buck GA, Denson T, Spence JE, Hymes J, Wolf B: Human serum biotinidase. cDNA cloning, sequence, and characterization. J Biol Chem. 1994 Mar 4;269(9):6566-70.
Pubmed: 7509806
Knight HC, Reynolds TR, Meyers GA, Pomponio RJ, Buck GA, Wolf B: Structure of the human biotinidase gene. Mamm Genome. 1998 Apr;9(4):327-30.
Pubmed: 9530634
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z: Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. Genome Res. 2000 Oct;10(10):1546-60. doi: 10.1101/gr.140200.
Pubmed: 11042152
Kalies KU, Hartmann E: Membrane topology of the 12- and the 25-kDa subunits of the mammalian signal peptidase complex. J Biol Chem. 1996 Feb 16;271(7):3925-9. doi: 10.1074/jbc.271.7.3925.
Pubmed: 8632014
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