Home > Newborn Disorders > Carnitine uptake deficiency
Carnitine uptake deficiency
Screening
Tested By
tandem mass spectrometry (MS/MS); sensitivity=100% (80% with the first screen only [Nicola Longo, personal communication 2006]); specificity=99.97% [Schulze: 2003]Names
Carnitine uptake deficiency
CUD
Carnitine uptake defect
Carnitine transporter deficiency
Systemic carnitine deficiency (SCD)
Primary carnitine deficiency
Overview
Carnitine transporter enzyme deficiency results in urinary carnitine wasting and systemic and intracellular carnitine deficiency. The latter results in an intramitochondrial defect in the beta-oxidation of fatty acids that impairs energy production and causes accumulation of free fatty acids. The increased reliance on fat metabolism for energy production during prolonged fasting and/or periods of increased energy demands (fever, stress, lack of sleep) may cause metabolic crises in patients with carnitine deficiency.Prevalence
1/40,000 [Koizumi: 1999], with about 1% of the normal US population being heterozygous for this condition [Amat: 2008]Prenatal Testing
DNA testing and functional assay (carnitine transport) in cells obtained by amniocentesis or CVS.Clinical Characteristics
With treatment prior to metabolic crises, outcomes should be normal. Treatment may reverse pre-existing cardiomyopathy and muscle weakness, but not developmental delay. Without treatment, symptoms may begin between birth and three years of age or, in the myopathic form, symptoms usually begin before seven years and may not include metabolic crisis episodes or hypoglycemia. Some children remain asymptomatic for life. Patients are at risk of sudden death from arrhythmia at any age.Inital signs and symptoms may include:
- poor appetite
- vomiting
- irritability
- lethargy
- hypoketotic hypoglycemia
- sudden death
- lab findings:
- anemia,
- metabolic acidosis, and
- hypoglycemia.
Subsequent finding include:
- muscle weakness
- cardiomyopathy
- cardiac arrhythmia
- hepatomegaly
- seizures and
- brain injury from hypoglycemia
Treatment consists of carnitine supplementation. Mothers with primary carnitine deficiency can be identified by newborn screening of their unaffected infant.[Schimmenti: 2007]
Follow-up on positive screening test
Plasma and urine carnitine analysis (the latter to measure urinary carnitine reabsorption), carnitine transporter functional analysis in fibroblasts and/or OCTN2 gene sequencing.Primary care management
Upon notification of the + screen
- Contact the family and evaluate the infant for poor feeding, lethargy, tachycardia;
- Provide emergency treatment/referral for signs of hypoglycemia, lethargy, tachycardia, hepatomegaly (see the ACT Sheet for Carnitine uptake defect (ACMG)
(
344 KB)
for additional information);
- 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 Carnitine uptake deficiency info for parents (STAR-G));
- Special diet is not required but frequent feedings and avoidance of fasting is important;
- Oral L-carnitine supplements should be continued for life;
- For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.
Specialty Care Collaboration
Initial consultation and ongoing collaboration if the child is affected. A dietician may work with the family to devise an optimal approach to dietary management.Resources
Information & Support
For Professionals
Carnitine uptake deficiency info for professionals (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, one of a series of Disorder Fact Sheets for Professionals;
structured list of information about the condition, with links to more information.
ACT Sheet for Carnitine uptake defect (ACMG)
( 344 KB)
Developed by the American College of Medical Genetics (ACMG), includes recommended responses to positive newborn screening
test results, diagnostic evaluation, clinical expectations, and sources of additional information. See the ACMG ACT Sheets
and Confirmatory Algorithms (link elsewhere on this page) for more info and sheets on other conditions.
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 carnitine uptake 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.
Carnitine uptake deficiency (OMIM)
Extensive review of the literature, including clinical features and genetics, 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.
Utah Newborn Screening Program
The site provides information and statistics about the program and related legislation, training for practices, and the conditions
screened for.
For Parents and Patients
Carnitine uptake deficiency info for parents (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, providing information for parents about carnitine
uptake deficiency and links to other sites including parent support groups.
Carnitine uptake deficiency (Genetics Home Reference)
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference
site.
Fatty Oxidation Disorders (FOD) Family Support Group
The FODsupport.org site offers a variety of information for families about fatty acid oxidation disorders, support groups,
coping, finances, and links to other sites.
National Newborn Screening & Genetics Resource Center
Provides information for families and professionals about genetic screening; links to support and advocacy groups; links to
state genetic contacts; newsletters; fact sheets; data reports; publications; and more.
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: | 3/2011 |
Page Bibliography
Amat di San Filippo C, Taylor MR, Mestroni L, Botto LD, Longo N.
Cardiomyopathy and carnitine deficiency.
Mol Genet Metab..
2008;94(2):162-166.
Carnitine is essential for the transfer of long-chain fatty acids across the mitochondrial membrane for subsequent beta-oxidation.
Study results indicate heterozygosity for primary carnitine deficiency is not more frequent in patients with unselected types
of cardiomyopathy and is unlikely to be an important cause of cardiomyopathy in humans.
Koizumi A, Nozaki J, Ohura T, Kayo T, Wada Y, Nezu J, Ohashi R, Tamai I, Shoji Y, Takada G, Kibira S, Matsuishi T, Tsuji A.
Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese
pedigrees with primary systemic carnitine deficiency.
Hum Mol Genet.
1999;8(12):2247-54.
PubMed abstract
Schimmenti LA, Crombez EA, Schwahn BC, Heese BA, Wood TC, Schroer RJ, Bentler K, Cederbaum S, Sarafoglou K, McCann M, Rinaldo
P, Matern D, di San Filippo CA, Pasquali M, Berry SA, Longo N.
Expanded newborn screening identifies maternal primary carnitine deficiency.
Mol Genet Metab.
2007;90(4):441-5.
PubMed abstract
Primary carnitine deficiency impairs fatty acid oxidation and can result in hypoglycemia, hepatic encephalopathy, cardiomyopathy
and sudden death. Given the lifetime risk of morbidity or sudden death, identification of adult patients with primary carnitine
deficiency is an added benefit of expanded newborn screening programs.
Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF.
Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome,
and implications.
Pediatrics.
2003;111(6 Pt 1):1399-406.
PubMed abstract