Peroxisomal disorders: Pathology review

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Peroxisomal disorders: Pathology review

USMLE® Step 1 questions

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USMLE® Step 1 style questions USMLE

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A 24-year old man presents to his primary care physician’s clinic due to increasing weakness in his legs for the last three years. He notes that his legs feel very stiff. He reports that he had a maternal uncle with similar issues. On physical exam, the patient has decreased vibratory sensation in the bilateral lower extremities. He exhibits signs of early male pattern baldness. The physician confirms the suspected diagnosis via testing the patient’s plasma for accumulated very-long-chain fatty acids (VLCFA) and a mutation in the ABCD1 gene. Which of the following organelles is affected in this patient’s disease?  


8 month old Emmanuel is brought to the clinic due to repeated episodes of jerking movements and loss of consciousness over the past few months. His parents are also worried because he feels limp when they lift him up, and his head tends to flop backward or to the side. On physical examination, you notice he has a flat face with a broad nasal bridge, and upon palpation of the abdomen, the liver appears enlarged. Right after him, 17 year old Arletta comes in. She complains that, recently, she has started to have difficulties seeing clearly at night. She also noticed that her skin is unusually dry, and doesn’t seem to improve with moisturizing cream. On physical examination, there are rough scaly patches of skin all over her body. You also notice that both her fourth toes are shorter than normal, and she tells you that they’ve been like that since birth. Finally, you see 32 year old George, who comes in with a 6 month history of progressive fatigue and weight loss. His wife has also recently noticed that, on occasion, he has been slurring his speech. On further questioning, George reluctantly tells you that he has experienced difficulties maintaining an erection. Examination reveals a low blood pressure, along with increased skin pigmentation, mostly around the oral mucosa, palmar creases, and knuckles.

Based on the initial presentation, Emmanuel, Arletta,, and George all seem to have some form of peroxisomal disorder. But first a bit of physiology real quick. Peroxisomes are cellular organelles that neutralize free radicals, which are molecules with an unpaired electron that can damage the cells by oxidizing lipids, proteins, and even the DNA. When free radicals enter peroxisomes, they get converted by an enzyme called oxidase into hydrogen peroxide or H2O2. But since hydrogen peroxide is still dangerous, there’s another enzyme, called catalase, which safely converts it into water and oxygen. Another thing catalase can do is use that hydrogen peroxide to break down toxic substances like ethanol and formaldehyde. That’s why you would expect liver cells to have more peroxisomes than most other cells in the body.

Peroxisomes also play an important role in two types of fatty acid oxidation: beta oxidation, where linear fatty acids called very long chain fatty acids, or VLCFAs for short, and medium chain fatty acids, or MCFAs for short, are chopped down into progressively smaller chains; and alpha oxidation, where branched chain fatty acids are broken down into linear ones, which can then undergo beta oxidation. For your exams, what’s important to know is that alpha oxidation takes place exclusively within peroxisomes, while beta oxidation can also occur in the mitochondria. It’s important to remember that peroxisomes are responsible for the beta oxidation of very long chain fatty acids, while mitochondria can only work with medium chain fatty acids. Now, the thing is that one of the byproducts of both alpha and beta oxidation is hydrogen peroxide, so catalase is used once again to convert it into water and oxygen.


  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. "Biochemistry of Mammalian Peroxisomes Revisited" Annual Review of Biochemistry (2006)
  4. "Peroxisomal disorders: The single peroxisomal enzyme deficiencies" Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (2006)
  5. "Peroxisome biogenesis disorders" Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (2006)
  6. "The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum" Molecular Genetics and Metabolism (2004)
  7. "The Metabolic & Molecular Bases of Inherited Disease" New York ; Montreal : McGraw-Hill (2001)
  8. "Mutational Analyses on X-Linked Adrenoleukodystrophy Reveal a Novel Cryptic Splicing and Three Missense Mutations in the ABCD1 Gene" Pediatric Neurology (2013)

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