LCHADD/TFP Deficiency - Description

Other Names

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


277.85, disorders of fatty acid oxidation

The ICD-9-CM code 277.85 includes several disorders of fatty acid oxidation, of which LCHADD is one. Also see LCHADD/TFP ICD9 (PDF Document 70 KB) for codes for related complications.


Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a disorder of fatty acid oxidation. During times of fasting, the body uses fat as a major source of energy. Fats are catabolized through a process called beta-oxidation. The overall reaction involves several different enzymes which break down very-long chain fats to long-chain fats, long-chain fats to medium-chain fats, eventually resulting in ketone bodies and acetyl-CoA. The former are used directly for energy and the latter enter the Kreb cycle to generate ATP and reducing equivalents.

Long-chain fatty acids are broken down by the trifunctional protein (TFP) after initial metabolism by very-long chain acyl CoA dehydrogenase. This protein catalyzes 3 steps (for which it got its name) in the beta-oxidation of fatty acids, including the hydratase, long-chain 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase activity. The trifunctional protein is formed by two subunits (alpha and beta) encoded by two different genes (HADA and HADB) located on the same chromosome (2p23). 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 gene) or beta subunit (HADB gene); LCHADD is caused by specific missense mutations in the alpha subunit that allow the reaction to start but not to be completed. LCHADD 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.

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
  • hepatomegaly
  • 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/myopathy
Even with treatment, individuals with LCHADD and TFP deficiency may still have symptoms that may include episodes of hypoketotic hypoglycemia, rhabdomyolysis, retinitis pigmentosa, and axonal neuropathy. Treatment mainly involves avoiding fasting, following strict dietary recommendations, and using supplements as needed.


LCHADD and trifunctional protein deficiency are inherited in an autosomal recessive manner. Prenatal testing can be performed by DNA testing in cells obtained by amniocentesis or chorionic villous sampling (CVS). Relevant laboratories can be found at Genetic Testing Resources for LCHADD (GeneTests). See also LCHADD/TFP Deficiency in the Newborn Disorders section.


Prognosis varies depending on whether there is LCHADD alone or trifunctional protein deficiency. Symptoms may begin at birth or take a few years to present, and may be mild or severe. The main goal of treatment is to avoid progression of the disease and acute decompensations brought about by illness, fasting and dehydration. 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, and if not treated, may result in death. Neuropathy is significant in patients with trifunctional protein deficiency. Even with treatment, most patients with LCHAD deficiency suffer episodic hypoketotic hypoglycemia and rhabdomyolysis.


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

Pearls And Alerts

On Treatment And Management Page

Fasting, dehydration, and illness

Helpful Articles

PubMed search for trifunctional protein deficiency (MTP or TFP), last 5 years

Wilcken B.
Fatty acid oxidation disorders: outcome and long-term prognosis.
J Inherit Metab Dis. 2010. PubMed abstract

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

LCHADD/TFP Deficiency Module Authors

Author: Nicola Longo, MD, Ph.D. - 3/2011
Compiled and edited by: Lynne M Kerr, MD, Ph.D. - 3/2011
Content Last Updated: 3/2011

The authors listed above are responsible for the overall LCHADD/TFP Deficiency Module. Authors contributing to individual pages in the module are listed on those pages.

Page Bibliography

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