Home > Newborn Disorders > Holocarboxylase/multiple carboxylase deficiency
Holocarboxylase/multiple carboxylase deficiency
Screening
Names
Holocarboxylase/multiple carboxylase deficiency
MCD
Holocarboxylase synthetase deficiency (HCSD)
Holocarboxylase deficiency
Overview
Caused by a a defect in holocarboxylase synthetase which is responsible for attaching biotin to four biotin-dependent enzymes, propionyl CoA carboxylase, beta-methylcrotonyl CoA, carboxylase, acetyl-CoA carboxylase, and pyruvate carboxylase. The loss of function of these enzymes impairs gluconeogenesis, results in the accumulation of multiple organic acids, in the pathways of propionic acid and leucine catabolism. This leads to inadequate energy production and the accumulation of toxic compounds leading to metabolic acidosis and other problems. Other forms of multiple carboxylase deficiency may be due to defective biotin absorption or transport or to biotinidase deficiency that in the past was known as late-onset multiple carboxylase deficiency.Prevalence
about 1/87,000 live births [Holocarboxylase/multiple carboxylase deficiency (Genetics Home Reference)]Clinical Characteristics
With treatment, most children will have normal growth and development, though some have only partly or not responded to therapy. Without treatment, repeated episodes of metabolic acidosis lead to severe impairment or death. Infants may begin to show symptoms within a few hours or days of life while other infants may not have symptoms till two years of age. Children may be healthy between metabolic crisis episodes.Initial signs/symptoms may include:
- poor feeding
- vomiting
- skin rashes
- lethargy
- lab findings:
- metabolic acidosis
- hyperammonemia
- keturia
- thrombocytopenia
- hypoglycemia
- elevated organic acid levels in the blood and urine
If not treated promptly, patients may experience:
- difficulty breathing
- alopecia
- motor skill delays
- hearing loss
- speech loss
- spasticity
- problems with coordination
- seizures
- brain damage
- death
Treatment consists of bioting at high doses (20-300 mg per day), fasting avoidance and prompt treatment of infections, fever, gastroenteritis with fluids containing glucose.
Follow-up on positive screening test
Quantitative plasma acylcarnitine profile, serum biotinidase assay, urine organic acids. Definitive confirmation requires enzyme assay in white blood cells or fibroblasts or DNA testing. Enzyme assay might miss mild forms due to the presence of biotin in culture media.Primary care management
Upon notification of the + screen
- Contact the family and evaluate the infant for poor feeding, vomiting, or lethargy;
- Provide emergency treatment/referral for signs/symptoms of hypoglycemia, metabolic acidosis, ketonuria, or seizures;
- To confirm the diagnosis, work with the following service(s): Utah Newborn Screening Program, (801-584-8256); See also Services below;
- For evaluation and ongoing collaborative management, consult the following service(s): Medical Genetics, (801-231-3599); See also Services below;
If the diagnosis is confirmed
- Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see Holocarboxylase/multiple carboxylase deficiency info for parents (STAR-G) for additional information)
- Biotin supplements are indicated
- For those identified after irreversible consequences, assist in management, particularly developmental and educational interventions
Specialty Care Collaboration
Initial consultation and ongoing collaboration, particularly for dietary management. Genetic counseling for the family.Resources
Information & Support
For Professionals
ACT Sheet for Elevated C5-OH Acylcarnitine (ACMG)
(
400 KB)
Developed by the American College of Medical Genetics, includes recommended responses to positive newborn screening test results,
diagnostic evaluation, clinical expectations, and sources of additional information.
ACT Sheets and Confirmatory Algorithms (ACMG)
The American College of Medical Genetics (ACMG) has developed ACTion (ACT) Sheets and algorithms for responding to positive
newborn screening test results. This page contains a table with links to all of the ACT Sheets and related algorithms.
Resources for Holocarboxylase/multiple carboxylase deficiency (NLM)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; from the National
Library of Medicine and the Genetic Alliance.
Holocarboxylase/multiple carboxylase deficiency (OMIM)
From the Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University, providing technical information for
providers on genetic disorders, links to MEDLINE, and links to other scientific information and sites.
Holocarboxylase/multiple carboxylase deficiency Fact Sheet (Iowa Dept. of Health)
( 21 KB)
This fact sheet, developed by the Iowa Department of Health, provides information for parents and professionals.
For Parents and Patients
Holocarboxylase/multiple carboxylase deficiency info for parents (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, providing information for parents about holocarboxylase/multiple
carboxylase deficiency and links to other sites including parent support groups.
Holocarboxylase/multiple carboxylase deficiency (Genetics Home Reference)
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference
site.
Organic Acidemia Association (OAA)
A non-profit organization that provides information for parents and providers; newsletters; event information; connections
with other parents; a listserv; a discussion board; information about nutrition and recipes; translation of their web pages
into five other languages; hosting of the Propionic Acidemia Research Network and other research funds; and links to other
sites.
Services
Newborn Screening Programs
Utah Newborn Screening Program,
more info...
44 Mario Capecchi Drive
Salt Lake City, UT 84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening
Pediatric Medical Genetics
See all Pediatric Medical Genetics services providers (3) in our database.
For other services related to this condition, browse our Services categories or search our database.
Authors
| Reviewing Author: | Nicola Longo MD, PhD, 3/2011 |
| Compiled and edited by: | Alfred Romeo RN, PhD, 3/2007 |
| Content Last Updated: | 4/2011 |