NEWBORN SCREENING

[Elevated C16-OH +/- C18:1-OH and Other Long Chain Acylcarnitines]

Trifunctional Protein Deficiency (TFP)

 

Differential Diagnosis: Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency; Trifunctional protein (TFP) deficiency. 

Condition Description: LCHAD and TFP deficiencies are fatty acid oxidation (FAO) disorders. FAO occurs during prolonged fasting and/or periods of increased energy demands (fever, stress) after glycogen stores become depleted and energy production relies increasingly on fat metabolism. Fatty acids and potentially toxic derivatives accumulate in FAO disorders which are caused by deficiency in one of the enzymes involved in FAO. 

YOU SHOULD TAKE THE FOLLOWING IMMEDIATE ACTIONS:

  • Contact family to inform them of the newborn screening result and ascertain clinical status (poor feeding, vomiting, lethargy)
  • Consult with pediatric metabolic specialist
  • Evaluate the newborn (hepatomegaly, cardiac insufficiency, history of sudden unexpected death in a sibling; maternal liver disease during pregnancy; hypoglycemia).  If signs are present or if infant is ill, initiate emergency treatment in consultation with metabolic specialist
  • Educate family about signs and symptoms of hypoglycemia and metabolic acidosis
  • Report findings to state newborn screening program (Carleigh Soule at 307-777-6297)  

Confirmation of Diagnosis: Hypoglycemia, elevated liver transaminases, bilirubin, lactate, ammonia, and creatine phosphokinase (CPK) are suggestive of LCHAD and TFP deficiencies. Plasma acylcarnitine and urine organic acid analysis are first-line tests to determine if the appropriate LCHAD/TFP profiles are present. Differentiation between both disorders requires further biochemical and molecular genetic testing in cultured fibroblasts derived from a skin biopsy. 

Clinical Considerations: LCHAD and TFP deficiencies typically present acutely and are associated with high mortality unless treated promptly; milder variants exist. Hallmark features include hepatomegaly, cardiomyopathy, lethargy, hypoketotic hypoglycemia, elevated liver transaminases, lactic acidosis, and failure to thrive. 

Additional Information: (Click on the name to take you to the website) 

Genetic Home Reference                                       Wyoming Department of Health
http://ghr.nlm.nih.gov                                           http://www.health.wyo.gov  

Star G and HRSA                                                   Colorado Newborn Screening
http://www.newbornscreening.info/                        http://www.cdphe.state.co.us   

American Academy of Pediatrics                                                                                    http://pediatrics.aappublications.org/

 

www.acmg.net

 

For Algorithm: http://www.acmg.net/resources/policies/ACT/Visio-C16-OH+_C18-1-OH_(4-29-06).pdf