LCHAD/TFP Deficiency

Guidance for primary care clinicians receiving a positive newborn screen result

Other Names

Long chain 3 hydroxyacyl-CoA dehydrogenase deficiency
Trifunctional protein deficiency (TFP)

ICD-10 Coding

E71.310, Long chain/very long chain acyl CoA dehydrogenase deficiency

Disorder Category

Fatty acid oxidation disorder


Abnormal Finding

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

Tested By

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


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. It is formed by 2 subunits encoded by 2 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 (TFP) 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 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.

Clinical Characteristics

With treatment prior to hypoglycemic crises, the child’s intelligence is likely to be normal, but progression of peripheral neuropathy and retinitis pigmentosa can occur. [García: 2021]
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 more frequent and usually occurs earlier in patients with trifunctional protein deficiency. Symptoms, whether mild or severe, may begin anytime between birth and 3 years of age. All patients have exercise intolerance and develop myoglobinuria and muscle pain with strenuous exercise.

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


The incidence of LCHAD deficiency in the United States is approximately 1:363,738. [Therrell: 2014]


Autosomal recessive

Primary Care Management

Next Steps After a Positive Screen

  • Contact the family and evaluate the infant for hepatomegaly or cardiomyopathy. Ask about a family history of sudden death or a maternal history of pregnancy-related liver disease, such as hemolysis, elevated liver enzymes, low platelets (HELLP syndrome), or acute fatty liver of pregnancy (ALFP).
  • Provide emergency treatment and referral for symptoms of hypoglycemia, lethargy, or feeding problems.

Confirming the Diagnosis

  • To confirm diagnosis, work with Newborn Screening Services (see NM providers [1]).
  • Follow-up testing includes quantitative plasma acylcarnitine profile, urine organic acid analysis, free 3-OH-fatty acids, and biochemical and molecular genetic testing in blood for differentiation between LCHADD and TFP.

If the Diagnosis is Confirmed

  • Consult Medical Genetics (see NM providers [4]) for further advice or evaluation.
  • Educate the family about the signs and symptoms of hypoglycemia, and the need for urgent care if the infant becomes ill. See LCHAD/TFP Deficiency - Information for Parents (STAR-G) for additional information).
  • Support avoidance of fasting, use of uncooked starch, medium chain triglycerides, and frequent, low fat and high carbohydrate meals and snacks.
  • Consider oral L-carnitine (at low doses) and docosahexaenoic acid (DHA)/essential fatty acids supplements.
  • Assist in management of irreversible consequences as necessary, particularly with developmental and educational interventions.
  • See the Portal’s diagnosis and management module for LCHAD/TFP Deficiency.

Specialty Care Collaboration

Provide 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.


Information & Support

For Professionals

LCHAD 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

LCHAD/TFP 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.

Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.

Mitochondrial Trifunctional Protein Deficiency (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.

Fatty Oxidation Disorders (FOD) Family Support Group
Information for families about fatty acid oxidation disorders, support groups, coping, finances, and links to other sites.


ACT Sheet for LCHAD and TFP Deficiencies (ACMG) (PDF Document 333 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Confirmatory Algorithm for LCHAD and TFP Deficiencies (ACMG) (PDF Document 69 KB)
Resource for clinicians to help confirm diagnosis; American College of Medical Genetics.

Long Chain Hydroxy Acyl-CoA Dehydrogenase Deficiency (LCHADD) (NECMP)
A guideline for health care professionals treating the sick infant or child who has been diagnosed with LCHADD.

Services for Patients & Families in New Mexico (NM)

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.


LCHAD/TFP Deficiency in Children (birth-17 years) (
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.

Helpful Articles

PubMed search for LCHAD/TFP deficiency and neonatal screening, last 10 years

De Biase I, Viau KS, Liu A, Yuzyuk T, Botto LD, Pasquali M, Longo N.
Diagnosis, Treatment, and Clinical Outcome of Patients with Mitochondrial Trifunctional Protein/Long-Chain 3-Hydroxy Acyl-CoA Dehydrogenase Deficiency.
JIMD Rep. 2017;31:63-71. PubMed abstract / Full Text

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 & Reviewers

Initial publication: March 2007; last update/revision: July 2017
Current Authors and Reviewers:
Author: Nicola Longo, MD, Ph.D.
Authoring history
2011: first version: Nicola Longo, MD, Ph.D.A
AAuthor; CAContributing Author; SASenior Author; RReviewer

Page Bibliography

García García LC, Zamorano Martín F, Rocha de Lossada C, García Lorente M, Luque Aranda G, Escudero Gómez J.
Retinitis pigmentosa as a clinical presentation of LCHAD deficiency: A clinical case and review of the literature.
Arch Soc Esp Oftalmol (Engl Ed). 2021;96(9):496-499. PubMed abstract

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

Therrell BL Jr, Lloyd-Puryear MA, Camp KM, Mann MY.
Inborn errors of metabolism identified via newborn screening: Ten-year incidence data and costs of nutritional interventions for research agenda planning.
Mol Genet Metab. 2014;113(1-2):14-26. PubMed abstract / Full Text