Holocarboxylase synthetase deficiency
Reviewed June 2007
What is holocarboxylase synthetase deficiency?
Holocarboxylase synthetase deficiency is an inherited disorder in which the body is unable to use the vitamin biotin effectively. This disorder is classified as a multiple carboxylase deficiency, a group of disorders characterized by impaired activity of certain enzymes that depend on biotin.
The signs and symptoms of holocarboxylase synthetase deficiency typically appear within the first few months of life, but the age of onset varies. Affected infants often have difficulty feeding, breathing problems, a skin rash, hair loss (alopecia), and a lack of energy (lethargy). Immediate treatment and lifelong management with biotin supplements may prevent many of these complications. If left untreated, the disorder can lead to delayed development, seizures, and coma. These medical problems may be life-threatening in some cases.
How common is holocarboxylase synthetase deficiency?
The exact incidence of this condition is unknown, but it is estimated to affect 1 in 87,000 people.
What genes are related to holocarboxylase synthetase deficiency?
Mutations in the HLCS gene cause holocarboxylase synthetase deficiency.
The HLCS gene provides instructions for making an enzyme called holocarboxylase synthetase. This enzyme is important for the effective use of biotin, a B vitamin found in foods such as liver, egg yolks, and milk. Holocarboxylase synthetase attaches biotin to certain enzymes that are essential for the normal production and breakdown of proteins, fats, and carbohydrates in the body. Mutations in the HLCS gene reduce the enzyme's ability to attach biotin to these enzymes, preventing them from processing nutrients properly and disrupting many cellular functions. These defects lead to the serious medical problems associated with holocarboxylase synthetase deficiency.
How do people inherit holocarboxylase synthetase deficiency?
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Where can I find information about treatment for holocarboxylase synthetase deficiency?
You may find information on treatment or management of holocarboxylase synthetase deficiency or some of its symptoms in the links below, particularly the links for
MedlinePlus Encyclopedia, Educational resources, and Patient support.
Where can I find additional information about holocarboxylase synthetase deficiency?
You may find the following resources about holocarboxylase synthetase deficiency helpful. These materials are written for the general public.
- MedlinePlus - Health information
- Encyclopedia: Pantothenic Acid and Biotin (http://www.nlm.nih.gov/medlineplus/ency/article/002410.htm)
- Health Topic: Metabolic Disorders (http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html)
- Health Topic: Newborn Screening (http://www.nlm.nih.gov/medlineplus/newbornscreening.html)
- Educational resources - Information pages
- Northwest Regional Newborn Screening Program (http://oregon.gov/DHS/ph/nbs/docs/holocarboxylase.pdf)
- Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=148)
- Screening, Technology, and Research in Genetics (http://www.newbornscreening.info/Parents/organicaciddisorders/HCSD.html)
- Virginia Department of Health (http://www.vahealth.org/genetics/documents/ParentfactsPDF/Multiple%20CoA%20Carboxylase%20Deficiency%20-%20Parent%20Fact%20Sheet.pdf)
- Patient support - For patients and families
- Children Living with Inherited Metabolic Diseases (http://www.climb.org.uk/)
- Family Village: Metabolic Disorders (http://www.familyvillage.wisc.edu/lib_meta.htm)
- Organic Acidemia Association (http://www.oaanews.org/mcd.htm)
- Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/metaboli.html)
- Save Babies Through Screening Foundation, Inc. (http://www.savebabies.org/diseasedescriptions/multiplecoacarboxylase.php)
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for holocarboxylase synthetase deficiency?
- Early-Onset Biotin-Responsive Multiple Carboxylase Deficiency
- Early-Onset Combined Carboxylase Deficiency
- HLCS deficiency
- Infantile Multiple Carboxylase Deficiency
- Multiple Carboxylase Deficiency, Neonatal Form
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What if I still have specific questions about holocarboxylase synthetase deficiency?
- See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
- Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
- Submit your question to Ask the Geneticist (http://www.askthegen.org/).
What glossary definitions help with understanding holocarboxylase synthetase deficiency?
aciduria ;
alopecia ;
autosomal ;
autosomal recessive ;
biotin ;
carbohydrate ;
carboxylase ;
cell ;
coma ;
complication ;
deficiency ;
egg ;
enzyme ;
gene ;
incidence ;
lethargy ;
mutation ;
neonatal ;
newborn screening ;
protein ;
recessive ;
screening ;
seizure ;
sign ;
symptom ;
synthetases ;
vitamins
You may find definitions for these and many other terms in the Genetics Home Reference
Glossary (http://ghr.nlm.nih.gov/glossary).
References
- Emery, Alan E H; Rimoin, David L; Emery & Rimoin's principles and practice of medical genetics.; 4th ed. / edited by David L. Rimoin ... [et al.]; London ; New York : Churchill Livingstone, 2002. p2552-2553.
- Morrone A, Malvagia S, Donati MA, Funghini S, Ciani F, Pela I, Boneh A, Peters H, Pasquini E, Zammarchi E. Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency. Am J Med Genet. 2002 Jul 22;111(1):10-8. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12124727)
- Northwest Regional Newborn Screening Program (http://oregon.gov/DHS/ph/nbs/docs/holocarboxylase.pdf)
- Scriver, Charles R; The metabolic & molecular bases of inherited disease; 8th ed.; New York : McGraw-Hill, c2001. p3944-3947.
- Tang NL, Hui J, Yong CK, Wong LT, Applegarth DA, Vallance HD, Law LK, Fung SL, Mak TW, Sung YM, Cheung KL, Fok TF. A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency. Clin Biochem. 2003 Mar;36(2):145-9. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12633764)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
healthcare professional.
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
|
Indicates a page outside Genetics Home Reference.