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 ( 70 KB) for codes for related complications.
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
- cardiac insufficiency
- lab findings: elevated liver function tests, elevated CK, metabolic acidosis, lactic acidosis, hypoglycemia
- hepatic disease
- cardiac conduction defects (arrhythmia)
- peripheral neuropathy
- pigmentary retinopathy
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
|Author:||Nicola Longo, MD, PhD - 3/2011|
|Compiled and edited by:||Lynne M Kerr, MD, PhD - 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.
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