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Screening & Prevention >> Newborn Screening >> Fatty Acid Oxidation Disorders >> LCHAD

LCHAD

Disorder Category

a fatty acid oxidation disorder

Screening

Finding

elevated C16-OH +/- and C18:1-OH

Tested By

tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=100% [Schulze: 2003]

Names

LCHAD

Long chain 3 hydroxyacyl-CoA dehydrogenase deficiency

LCHADD

Trifunctional protien deficiency (TFP) (variant)

ICD-9

277.85, Disorders of fatty acid oxidation

Overview

LCHAD is involved in the beta-oxidation of fatty acids within mitochondria. The enzyme is part of the mitochondrial trifunctional protein which serves as a catalyst for of the oxidation pathway. LCHAD deficiency results 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]

Inheritance

autosomal recessive

Prenatal Testing

DNA testing or fatty acid oxidation probe by amniocentesis or CVS.

Clinical Characteristics

With treatment prior to hypoglycemic crises, intelligence is likely to be normal, though there may be no improvment in pre-existing peripheral neuropathy. 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, and
    • hypoglycemia.


Without effective treatment, subsequent symptoms may include:
  • hepatic disease,
  • peripheral neuropathy,
  • pigmentary retinopathy, and
  • 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 for differentiation between LCHAD 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): Metabolic Clinic, (801-585-2457); 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 LCHAD info for parents, STAR-G for additional information);
  • Support initiation and maintenance of avoidance of fasting, use of uncooked starch, and frequent, low fat, and high carbohydrate meals and snacks;
  • Oral L-carnitine, medium chain triglyceride (MCT) oil, and docosahexanoic acid (DHA) supplements may be indicated;
  • For those identified after irreversible consequences, assist in management, particularly with low vision aids, developmental and educational interventions.

Specialty Care Management

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

Links

For Professionals

LCHAD info for professionals, STAR-G
On the Screening, Technology and Research in Genetics (STAR-G) site, 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 LCHAD from ACMG (pdf 114kb)
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.

ACMG ACT Sheets and Confirmatory Algorithms
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.

LCHAD Emergency Protocol
A protocol for management of the patient with a positive screen for LCHAD, from the New England Consortium of Metabolic Programs.

LCHAD, OMIM
Extensive review of the literature, including clinical features and gene therapy, 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

LCHAD info for parents, STAR-G
From the Screening, Technology and Research in Genetics (STAR-G) site, providing information for parents about LCHAD and links to other sites including parent support groups.

LCHAD, 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
Salt Lake City, UT84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening

Pediatric Genetics

Metabolic Clinic, more info...
100 Mario Capecchi Drive
Salt Lake City, UT84113
Phone: 801-585-2457
Fax: 585-7252
http://www.ped.med.utah.edu/divisions/divisions.htm

See all Pediatric Genetics services providers (3) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed search for articles on LCHAD in the last 5 years.

Authors

Reviewing Author: Nicola Longo MD, PhD, 3/2007
Compiled and edited by: Alfred Romeo RN, PhD, 3/2007
Content Last Updated: 3/2008

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
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