This week, we are sharing another USMLE® Step 1-style practice question to test your knowledge of medical topics. Today’s case involves a 5-month-old infant who was brought to a pediatrician for evaluation of failure to thrive. Upon physical examination, the patient has a weak cry and diffuse hypotonia. Hepatomegaly is present with abdominal palpation. The organelle affected in this patient’s condition is normally involved in which of the following cellular processes? Can you figure it out?
A 5-month-old male infant is brought to a pediatrician for evaluation of failure to thrive. The patient was recently adopted and has never been evaluated by a physician as far as the new parents are aware. According to the parents, the infant cannot grab objects or roll from a prone to supine position. He has also experienced several episodes of generalized seizure activity. He is at the 10th percentile for length and 5th percentile for weight. Temperature is 37.0°C (98.6°F), blood pressure is 80/53 mmHg, and pulse is 92/min. Upon physical examination, the patient has a weak cry and diffuse hypotonia. Hepatomegaly is present with abdominal palpation. Genetic analysis reveals a mutation in the PEX gene. The organelle affected in this patient’s condition is normally involved in which of the following cellular processes?
A. ɑ-oxidation of branched-chain fatty acidsB. Modification of proteins targeted for lysosomal degradation
C. Clearance of bronchopulmonary secretions via ciliary oscillations
D. Synthesis of amino acid chains
E. Synthesis of ATP via oxidative phosphorylation
Scroll down to find the answer!
The correct answer to today’s USMLE® Step 1 Question is…
A. ɑ-oxidation of branched-chain fatty acids
Before we get to the Main Explanation, let’s look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!
Incorrect answer explanations
The incorrect answers to today’s USMLE® Step 1 Question are…
B. Modification of proteins targeted for lysosomal degradation
Incorrect: The Golgi body is responsible for adding mannose-6-phosphate residues to proteins targeted for lysosomal degradation. In I-cell disease, the Golgi body fails to phosphorylate mannose residues, and proteins are secreted into the extracellular space. Patients with I-cell disease often present with coarse facial features, restricted joint mobility, and skeletal abnormalities. This disease is not associated with a PEX gene mutation.
C. Clearance of bronchopulmonary secretions via ciliary oscillations
Incorrect: Cilia assist in clearing bronchopulmonary secretions. Primary ciliary dyskinesia is an autosomal recessive condition characterized by immotile cilia. Patients are at risk of airway disease due to impaired mucociliary clearance. Around 50% of patients with this condition also have situs inversus. The patient in this vignette does not have a history of recurrent pulmonary infections.
D. Synthesis of amino acid chains
Incorrect: Ribosomes synthesize amino acid chains from mRNA. However, this patient is presenting with hypotonia, seizures, hepatomegaly, and a mutation in the PEX gene, which is more concerning for Zellweger disease – a peroxisomal disorder.
E. Synthesis of ATP via oxidative phosphorylation
Incorrect: The mitochondria contain the enzymes comprising the electron transport chain involved in synthesizing ATP via oxidative phosphorylation. Mitochondrial abnormalities can lead to myopathies and optic neuropathy. However, this patient is presenting with hypotonia, seizures, hepatomegaly, and a mutation in the PEX gene, which is more concerning for Zellweger disease – a peroxisomal disorder.
Main Explanation
This young child presents with hypotonia, hepatomegaly, and a history of seizures. Genetic testing reveals a PEX gene mutation. Together, these findings are consistent with Zellweger syndrome–a disease that occurs secondary to peroxisomal defects.
Peroxisomes are membrane-bound organelles involved in several critical cellular processes, including:
1. Neutralization of free radicals, which in turn protects cellular components such as DNA, lipids, and proteins from oxidative damage.
2. Breakdown of toxic substances including ethanol and formaldehyde. This process is performed by catalase and also helps convert H2O2 into water.
3. ɑ-oxidation, where branched-chain fatty acids are broken down into linear fatty acids.
4. β-oxidation, where linear very-long-chain fatty acids (VLCFAs) and medium-chain fatty acids (MCFAs) are enzymatically broken down into progressively smaller chains.
5. Breakdown of amino acids6. Synthesis of bile acids, cholesterol, and plasmalogens.
6. Synthesis of bile acids, cholesterol, and plasmalogens. plasmalogens.
Major Takeaway
Peroxisomes are membrane-bound organelles that perform an array of functions including ɑ-oxidation and β-oxidation of fatty acids, neutralization of free radicals, and breakdown of toxic substances like alcohol. Zellweger syndrome is a peroxisomal disorder which presents with hypotonia, seizures, hepatomegaly, and a mutation in the PEX gene.
References
Delille, H.K., Bonekamp, N.A., Schrader, M. (2006) Peroxisomes and disease- An Overview. International Journal of Biomedical Sciences. 2(4), 308-314. PMID: 23674998.
Elumalai, V., Pasrija, D. (2020) “Zellweger syndrome”. StatPearls [Internet]. Web Address: https://www.ncbi.nlm.nih.gov/books/NBK560676/.
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The United States Medical Licensing Examination (USMLE®) is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). Osmosis is not affiliated with NBME nor FSMB.
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