A 34-year-old man develops severe chest and abdominal pain while shopping in a mall. Paramedics arrive and find him in severe distress. Several minutes later, he suffers a cardiac arrest with pulseless electrical activity and cannot be resuscitated. Postmortem examination reveals an internal hemorrhage as the cause of death. Histochemical evaluation of the patient's tissues reveals a defect affecting a large extracellular glycoprotein. This protein is normally found abundantly in large blood vessels, periosteum, and zonular fibers of the lens and functions to form microfibrils by surrounding elastin. This patient most likely suffered from which of the following conditions?

Question

A 34-year-old man develops severe chest and abdominal pain while shopping in a mall.  Paramedics arrive and find him in severe distress.  Several minutes later, he suffers a cardiac arrest with pulseless electrical activity and cannot be resuscitated.  Postmortem examination reveals an internal hemorrhage as the cause of death.  Histochemical evaluation of the patient's tissues reveals a defect affecting a large extracellular glycoprotein.  This protein is normally found abundantly in large blood vessels, periosteum, and zonular fibers of the lens and functions to form microfibrils by surrounding elastin.  This patient most likely suffered from which of the following conditions?

Quizplus · Accepted Answer

11ec160b_36f9_93c8_9249_eb7f70914168_MD0001_00 Fibrillin-1 is a major component of microfibrils that form a sheath around elastin fibers. Microfibrils are abundant in blood vessels (eg, aortic media), periosteum, and the suspensory ligaments of the lens. Fibrillin in the extracellular space acts as a scaffold for deposition of elastin extruded from connective tissue cells. Defects in fibrillin-1 cause mechanical weakening in the connective tissues and abnormal activation of transforming growth factor beta. Marfan syndrome is caused by an inherited defect in the fibrillin-1 gene. Patients with Marfan syndrome can often be identified due to a characteristic body habitus, with long thin extremities, loose joints, and long fingers (arachnodactyly). The cause of death in Marfan syndrome is most often due to cardiovascular complications (eg, aortic root dilation, dissection, and rupture). (Choice A) Ehlers-Danlos syndrome is a collection of heritable disorders of connective tissue characterized by skin and joint hypermobility. Like those with Marfan syndrome, these patients are at risk for aortic rupture. However, Ehlers-Danlos syndrome affects the formation and extracellular structuring of collagen rather than microfibrils. (Choice B) Homocystinuria is a rare inherited metabolic disorder due to cystathionine synthase deficiency. It is characterized by very high circulating homocysteine levels, marfanoid habitus, and increased risk for premature atherosclerotic cardiovascular disease. (Choice D) Osteogenesis imperfecta results from defects in the genes encoding type I collagen, a major component of bones. Defects in type I collagen in osteogenesis imperfecta result in reduced bone mass and fragility fractures. Other manifestations of the disease include blue sclera, dental abnormalities, and hearing loss. (Choice E) Autosomal dominant polycystic kidney disease is a disorder of tubular epithelial cells. It causes enlargement of the kidneys with numerous parenchymal cysts. Patients are also at risk for cardiac valvular disorders and ruptured cerebral aneurysms. (Choice F) Deficiency of vitamin C (scurvy) causes impaired hydroxylation of proline and lysine residues in collagen. Clinical features include skin fragility, easy bleeding, and poor dentition. Educational objective: Marfan syndrome is due to a defect in fibrillin-1, an extracellular glycoprotein that acts as a scaffold for elastin. It is abundant in the zonular fibers of the lens, periosteum, and aortic media. Aortic root dilation with dissection and rupture is a common cause of death. __________ References: Molecular pathogenesis of Marfan syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/25863307)

A 34-Year-Old Man Develops Severe Chest and Abdominal Pain While