GTR Home > Conditions/Phenotypes > Mitochondrial trifunctional protein deficiency


The mitochondrial trifunctional protein, composed of 4 alpha and 4 beta subunits, catalyzes 3 steps in mitochondrial beta-oxidation of fatty acids: long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), long-chain enoyl-CoA hydratase, and long-chain thiolase activities. Trifunctional protein deficiency is characterized by decreased activity of all 3 enzymes. Clinically, classic trifunctional protein deficiency can be classified into 3 main clinical phenotypes: neonatal onset of a severe, lethal condition resulting in sudden unexplained infant death (SIDS; 272120), infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy (Spiekerkoetter et al., 2003). Some patients with MTP deficiency show a protracted progressive course associated with myopathy, recurrent rhabdomyolysis, and sensorimotor axonal neuropathy. These patients tend to survive into adolescence and adulthood (den Boer et al., 2003). See also isolated LCHAD deficiency (609016), which is caused by mutation in the HADHA gene. [from OMIM]

Associated genes

    Summary: hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit

  • Also known as: MSTP029, ECHB, MTPB, TP-BETA, HADHB
    Summary: hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), beta subunit

Clinical features

  • Small for gestational age
  • Myoglobinuria
  • Abnormality of the amniotic fluid
  • Generalized muscle weakness
  • Lactic acidosis
  • Hypoketotic hypoglycemia
  • Myalgia
  • Failure to thrive
  • Retinopathy
  • Pigmentary retinopathy
  • Muscular hypotonia
  • Global developmental delay
  • Congestive heart failure
  • Cardiomyopathy
  • Dilated cardiomyopathy
  • Hydrops fetalis
  • Hypoglycemia
  • Hyperammonemia
  • Hepatomegaly
  • Prenatal maternal abnormality
  • Respiratory failure
  • Elevated hepatic transaminases
  • Rhabdomyolysis
  • Peripheral neuropathy
  • Long chain 3 hydroxyacyl coA dehydrogenase deficiency
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