Home > Newborn Disorders > LCHADD/TFP deficiency
LCHADD/TFP deficiency
Screening
Tested By
tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=100% [Schulze: 2003]Names
LCHADD/TFP deficiency
Long chain 3 hydroxyacyl-CoA dehydrogenase deficiency
LCHAD deficiency
Trifunctional protein deficiency (TFP)
Overview
The trifunctional protein catalyzes 3 steps in the beta-oxidation of fatty acids, including the hydratase, long-chain 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase activity. It is formed by two subunits encoded by two different genes (HADA and HADB) located on the same chromosome (2p23). In LCHAD deficiency, specific missense mutations within the alpha subunit (HADA) cause the disease. Mutations that completely abolish the function of the protein cause trifunctional protein deficiency. TFP deficiency can be caused either by mutations in the alpha (HADA) or beta subunit (HADB), LCHAD is caused by specific missense mutations in the alpha subunit that allow the reaction to start but not to be completed. LCHAD and TFP deficiency cause cellular damage from accumulation of 3-OH-fatty acids, impaired energy production from longer chain fatty acids, and consequent hypoglycemic crises during prolonged fasting or increased energy demands, such as fever or other stress.Prevalence
about 1/250,000 live births. [Schulze: 2003] Incidence is likely higher in Finland where the carrier rate is 1:240. [LCHAD info for professionals (STAR-G)]Prenatal Testing
DNA testing in cells obtained by amniocentesis or chorionic villous sampling (CVS).Clinical Characteristics
With treatment prior to hypoglycemic crises, intelligence is likely to be normal, though there may be progression of peripheral neuropathy and retinitis pigmentosa. Without treatment, hypoglycemic episodes may lead to developmental delay and neurologic impairment. Cardiomyopathy and/or hepatic failure may result in death. Pigmentary retinopathy develops with time. Neuropathy is significant in patients with trifunctional protein deficiency. Symptoms may begin anytime between birth and 3 years, and may be mild or severe.Initial symptoms/signs may include:
- poor feeding
- vomiting
- lethargy
- hypotonia
- heptomegaly
- cardiac insufficiency
- cardiomyopathy
- lab findings:
- elevated liver function tests
- elevated CK
- metabolic acidosis
- lactic acidosis
- hypoglycemia
Without effective treatment, subsequent symptoms may include:
- hepatic disease
- cardiomyopathy
- cardiac conduction defects (arrhythmia)
- peripheral neuropathy
- pigmentary retinopathy
- rhabdomyolysis
Follow-up on positive screening test
Quantitative plasma acylcarnitine profile, urine organic acid analysis, free 3-OH-fatty acids, biochemical and molecular genetic testing in cultured fibroblasts derived from skin biopsy or white blood cells for differentiation between LCHADD and TFP.Primary care management
Upon notification of the + screen
- Contact the family and evaluate the infant for heptomegaly, cardiomyopathy, family history of sudden death, maternal history of pregnancy-related liver disease (HELLP syndrome [hemolysis, elevated liver enzymes, low platelets] or ALFP [acute fatty liver of pregnancy]);
- Provide emergency treatment/referral for symptoms of hypoglycemia, lethargy, feeding problems;
- To confirm diagnosis, work with the following service(s): Utah Newborn Screening Program, (801-584-8256); See also Services below;
- For further advice or evaluation, consult the following service(s): Medical Genetics, (801-231-3599); See also Services below;
If the diagnosis is confirmed
- Educate the family regarding signs andsymptoms of hypoglycemia, and the need for urgent care when the infant becomes ill (see LCHADD/TFP deficiency info for parents (STAR-G) for additional information);
- Support initiation and maintenance of avoidance of fasting, use of uncooked starch, medium chain triglycerides, and frequent, low fat, and high carbohydrate meals and snacks;
- Oral L-carnitine (at low doses) and docosahexanoic acid (DHA)/essential fatty acids supplements may be indicated;
- For those identified after irreversible consequences, assist in management, particularly with low vision aids, 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
LCHAD 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 LCHADD (ACMG)
(
333 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.
LCHADD Acute Illness Protocol
A guideline for healthcare professionals treating the sick infant/child who has previously been diagnosed with LCHADD; developed
under the direction of Dr. Harvey Levy, Senior Associate in Medicine/Genetics at Children’s Hospital Boston, and Professor
of Pediatrics at Harvard Medical School, for the New England Consortium of Metabolic Programs.
Resources for LCHAD 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.
LCHADD (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.
For Parents and Patients
LCHADD/TFP deficiency info for parents (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, providing information for parents about LCHAD and
links to other sites including parent support groups.
LCHADD (Genetics Home Reference)
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference
site.
Trifunctional protein 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.
Services
Newborn Screening Programs
Utah Newborn Screening Program,
more info...
44 Mario Capecchi Drive
PO bOX 144710
Salt Lake City, UT 84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening
For other services related to this condition, browse our Services categories or search our database.
Helpful Articles
PubMed search for articles on LCHAD Neonatal Screening within the last 5 years.
Gillingham MB, Purnell JQ, Jordan J, Stadler D, Haqq AM, Harding CO.
Effects of higher dietary protein intake on energy balance and metabolic control in children with long-chain 3-hydroxy acyl-CoA
dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency.
Mol Genet Metab.
2007;90(1):64-9.
PubMed abstract / Full Text
Authors
| Author: | Nicola Longo MD, PhD, 2/2011 |
| Compiled and edited by: | Alfred Romeo RN, PhD, 3/2007 |
| Content Last Updated: | 9/2010 |
Page Bibliography
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