Question 101: A 54-year-old man presents to his primary care physician with a 2-month-history of diarrhea. He says that he feels the urge to defecate 3-4 times per day and that his stools have changed in character since the diarrhea began. Specifically, they now float, stick to the side of the toilet bowl, and smell extremely foul. His past medical history is significant for several episodes of acute pancreatitis secondary to excessive alcohol consumption. His symptoms are found to be due to a deficiency in an enzyme. Which of the following enzymes is most likely deficient in this patient?
- A. Enterokinase
- B. Amylase
- C. Colipase
- D. Lipase (Correct Answer)
- E. Chymotrypsin
Explanation: ***Lipase***
- The patient's history of **recurrent pancreatitis** likely led to **exocrine pancreatic insufficiency**, reducing the production of digestive enzymes, particularly **lipase**.
- **Steatorrhea** (foul-smelling, floating, sticky stools) is a classic symptom of **fat malabsorption**, which occurs due to insufficient lipase for triglyceride digestion.
*Enterokinase*
- **Enterokinase** is an enzyme produced in the **duodenum** that activates trypsinogen to trypsin, which then activates other pancreatic proteases.
- A deficiency would primarily cause **protein malabsorption**, not the pronounced fat malabsorption (steatorrhea) seen in this patient.
*Amylase*
- **Amylase** is responsible for **carbohydrate digestion**.
- While chronic pancreatitis can lead to amylase deficiency, the primary symptom of this patient's diarrhea, steatorrhea, points more directly to **fat malabsorption** rather than carbohydrate malabsorption.
*Colipase*
- **Colipase** is a co-enzyme that helps **lipase** bind to the fat-water interface to digest triglycerides.
- While essential for fat digestion, lipase itself is the primary enzyme responsible, and a direct deficiency in colipase alone is less commonly implicated as the sole cause of severe steatorrhea than a general pancreatic enzyme insufficiency affecting lipase production.
*Chymotrypsin*
- **Chymotrypsin** is a **protease** primarily involved in **protein digestion**.
- A deficiency would lead to **protein malabsorption**, which typically presents with symptoms like muscle wasting and edema, rather than the prominent steatorrhea described.
Question 102: A 2-year-old boy is brought to the emergency department by his parents because of fever and recurrent episodes of jerky movements of his extremities for the past 6 hours. Pregnancy and delivery were uncomplicated, and development was normal until the age of 1 year. The parents report that he has had gradual loss of speech, vision, and motor skills over the past year. During this time, he has been admitted to the hospital three times because of myoclonic seizures. Physical examination shows hypertonicity of the upper and lower extremities. Fundoscopic examination shows pallor of the optic disc bilaterally. An MRI of the brain shows brain atrophy and hyperintensity of the periventricular and subcortical areas. Two days after admission, the patient dies. Histopathologic examination of the brain shows aggregation of globoid cells and loss of glial cells. The patient’s condition was most likely caused by a deficiency of which of the following enzymes?
- A. β-Galactocerebrosidase (Correct Answer)
- B. β-Glucocerebrosidase
- C. Arylsulfatase A
- D. Sphingomyelinase
- E. β-Hexosaminidase A
Explanation: ***β-Galactocerebrosidase***
- The clinical presentation, including the **rapid neurodegeneration** (loss of speech, vision, motor skills), **hypertonicity**, **optic disc pallor**, brain atrophy, and periventricular/subcortical hyperintensities on MRI, is highly consistent with **Krabbe disease**.
- The classic histopathologic finding of **globoid cells** (macrophages filled with undigested galactocerebroside) and **loss of glial cells** in the brain are pathognomonic for Krabbe disease, which is caused by a deficiency of **β-galactocerebrosidase**.
*β-Glucocerebrosidase*
- Deficiency of β-glucocerebrosidase causes **Gaucher disease**, which typically involves **hepatosplenomegaly**, **bone crises**, and **pancytopenia**.
- While some forms have neurological involvement, the characteristic globoid cells and rapid neurodegeneration seen here are not typical for Gaucher disease.
*Arylsulfatase A*
- Deficiency of arylsulfatase A leads to **metachromatic leukodystrophy (MLD)**, which also presents with **progressive neurological deterioration**, motor regression, and demyelination.
- However, MLD is characterized by the accumulation of **sulfatides** in white matter and detection of **metachromatic granules** in nerves and urine, not globoid cells.
*Sphingomyelinase*
- Deficiency of sphingomyelinase causes **Niemann-Pick disease**, which is characterized by **hepatosplenomegaly**, **cherry-red spots** in the macula (in type A), and foam cells in various tissues.
- The neurological symptoms and brain pathology in this child are not consistent with Niemann-Pick disease.
*β-Hexosaminidase A*
- Deficiency of β-hexosaminidase A causes **Tay-Sachs disease**, which presents with **progressive neurodegeneration**, **cherry-red spots** in the macula, and **exaggerated startle response**.
- While it causes loss of motor skills and vision, the severe demyelination with periventricular hyperintensities and globoid cells are not features of Tay-Sachs disease (which primarily involves ganglioside accumulation).
