Holocarboxylase/Multiple Carboxylase Deficiency
Screening
Description
Clinical Characteristics
Without treatment, repeated episodes of metabolic acidosis lead to severe impairment or death. Infants may show symptoms within a few hours or days of life, while other infants may not have symptoms until 2 years of age. Children may be healthy between metabolic crisis episodes.
- Poor feeding
- Vomiting
- Skin rashes
- Lethargy
- Hypotonia
- Irritability
- Lab findings:
- Metabolic acidosis
- Hyperammonemia
- Ketonuria
- Thrombocytopenia
- Hypoglycemia
- Elevated organic acid levels in the blood and urine
- Global developmental delay
- Alopecia
- Eczematous skin rash
- Hearing loss
- Hyperventilation/apnea
- Spasticity
- Seizures
- Brain damage
- Death
Primary Care Management
Next Steps After a Positive 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.
Confirming the Diagnosis
- To confirm the diagnosis, work with Newborn Screening Services (see RI providers [2]).
- Additional testing may include quantitative plasma acylcarnitine profile, serum biotinidase assay, and urine organic acids. Definitive confirmation requires enzyme assay in white blood cells, fibroblasts, or DNA testing. Enzyme assay may miss mild forms due to the presence of biotin in culture media.
If the Diagnosis is Confirmed
- For evaluation and ongoing collaborative management, consult Medical Genetics (see RI providers [4])
- Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see Holocarboxylase/Multiple Carboxylase Deficiency - Information 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.
Resources
Information & Support
Families can face a big change when their baby tests positive for a newborn condition. Find information about A New Diagnosis - You Are Not Alone; Caring for Children with Special Health Care Needs; Assistance in Choosing Providers; Partnering with Healthcare Providers; Top Ten Things to Do After a Diagnosis.
For Professionals
Holocarboxylase/Multiple Carboxylase Deficiency (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance
in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
For Parents and Patients
Support
Holocarboxylase/Multiple Carboxylase Deficiency - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received
an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.
Holocarboxylase/Multiple Carboxylase Deficiency (Medlineplus)
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, which is a group of disorders characterized by impaired
activity of certain enzymes that depend on biotin.
Organic Acidemia Association (OAA)
A nonprofit organization that provides information, support, events, connections with other parents, a discussion board,
and nutrition and recipe ideas.
Tools
RI ACT Sheet for HCS/MCD (ACMG) (
127 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive, along with resources
for consultation and patient education/support; from the American College of Genetics and Genomics
Confirmatory Algorithms for Elevated C5-OH (ACMG) ( 224 KB)
Basic steps involved in determining the final diagnosis of an infant with a positive newborn screen for this condition; American
College of Medical Genetics.
Services for Patients & Families in Rhode Island (RI)
| Service Categories | # of providers* in: | RI | NW | Other states (4) (show) | | NM | NV | OH | UT |
|---|---|---|---|---|---|---|---|---|---|
| Biochemical Genetics (Metabolics) | 3 | 1 | 1 | 2 | 1 | 3 | |||
| Medical Genetics | 4 | 1 | 2 | 5 | 1 | 6 | |||
| Newborn Screening Services | 2 | 1 | 3 | 2 | 1 | 3 | |||
For services not listed above, browse our Services categories or search our database.
* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.
Helpful Articles
Donti TR, Blackburn PR, Atwal PS.
Holocarboxylase synthetase deficiency pre and post newborn screening.
Mol Genet Metab Rep.
2016;7:40-4.
PubMed abstract / Full Text
León-Del-Río A.
Biotin in metabolism, gene expression, and human disease.
J Inherit Metab Dis.
2019;42(4):647-654.
PubMed abstract
Van Hove JL, Josefsberg S, Freehauf C, Thomas JA, Thuy le P, Barshop BA, Woontner M, Mock DM, Chiang PW, Spector E, Meneses-Morales
I, Cervantes-Roldán R, León-Del-Río A.
Management of a patient with holocarboxylase synthetase deficiency.
Mol Genet Metab.
2008;95(4):201-5.
PubMed abstract / Full Text
Page Bibliography
MedLinePlus.
Holocarboxylase synthetase deficiency.
National Library of Medicine; (2020)
https://medlineplus.gov/genetics/condition/holocarboxylase-synthetase-.... Accessed on Oct. 5, 2022.