Disorders of fatty acid metabolism: Pathology review

00:00 / 00:00



Disorders of fatty acid metabolism: Pathology review



Disorders of fatty acid metabolism: Pathology review

USMLE® Step 1 questions

0 / 2 complete


USMLE® Step 1 style questions USMLE

of complete

A 6-day-old infant is brought to a local emergency department after being found unresponsive by the patient’s parents. The neonate is promptly admitted to the NICU and is given D10 normal saline and a bicarbonate infusion. Overnight, the patient develops generalized seizure activity. An MRI performed the following day reveals hypoxic-ischemic encephalopathy. Initial laboratory findings and newborn screening results are demonstrated below. Which of the following is the most likely diagnosis?  


Two kids are brought to the clinic by their mothers. The first one’s Dalia, a 2 year old girl. Her mother is concerned because Dalia always seems to be tired and weak, and in general doesn’t eat much. On physical examination of the abdomen, you palpate an enlarged liver. You decide to run a blood test, which reveals that her blood glucose and ketone bodies are decreased, but what really stands out to you is that her carnitine levels are also really low.

After Dalia, you see Luca, a 3 year old boy who had a brief seizure earlier that day. Luca’s mother tells you that he’s had gastroenteritis for the past few days, so he’s been vomiting and not eating much. You decide to run a blood test, which also reveals low blood glucose and ketone bodies, but unlike Dalia, he has high levels of fatty acyl-carnitine.

Based on the initial presentation, both Dalia and Luca seem to have some fatty acid metabolism disorder. Now, let’s review fatty acid metabolism real quick. Normally, the body's main source of energy is the glucose we get from food. When glucose is running low, like with prolonged fasting or exercise, the body is able to obtain energy from stored fats.

The simplest form of fats are fatty acids, which are grouped by length into short, medium, long, and very long chain fatty acids. Short and medium chain fatty acids are primarily obtained from the diet, while long and very long chain fatty acids can be synthesized from acetyl-CoA by the liver and fat cells.

Now, keep in mind that acetyl-CoA is usually found in the mitochondrial matrix, whereas the enzymes required for fatty acid synthesis are all in the cytoplasm. For acetyl-CoA to cross the mitochondrial membranes and get to the cytoplasm, it first needs to combine with oxaloacetate to form citrate. Once in the cytoplasm, an enzyme called citrate lyase leaves citrate back into acetyl-CoA and oxaloacetate. This whole process is called the citrate shuttle.


  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Fetal Fatty Acid Oxidation Disorders, Their Effect on Maternal Health and Neonatal Outcome: Impact of Expanded Newborn Screening on Their Diagnosis and Management" Pediatric Research (2005)
  6. "A Fetal Fatty-Acid Oxidation Disorder as a Cause of Liver Disease in Pregnant Women" New England Journal of Medicine (1999)

Copyright © 2023 Elsevier, its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Cookies are used by this site.

USMLE® is a joint program of the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME). COMLEX-USA® is a registered trademark of The National Board of Osteopathic Medical Examiners, Inc. NCLEX-RN® is a registered trademark of the National Council of State Boards of Nursing, Inc. Test names and other trademarks are the property of the respective trademark holders. None of the trademark holders are endorsed by nor affiliated with Osmosis or this website.