A 42-year-old woman presents with progressive jaundice and hepatosplenomegaly (liver 4 cm below costal margin). She reports ataxia and vertical supranuclear gaze palsy. Vital signs: BP 118/76, HR 88, RR 16, Temp 37°C, SpO2 98%. Laboratory analysis reveals elevated serum cholestanol and unesterified cholesterol levels. Bone marrow examination shows sea-blue histiocytes. Genetic testing confirms NPC1 mutations. She denies recent alcohol use. Which mechanism best explains the pathophysiology of her condition?
- A)Increased LDL receptor-mediated cholesterol uptake with defective SREBP-2 feedback
- B)Accumulation of oxidized cholesterol esters in macrophages
- C)Blockade of hepatic bile acid synthesis secondary to cholestasis
- D)Impaired intracellular cholesterol trafficking from late endosomes/lysosomes to the endoplasmic reticulumGABARITO
- E)Defective cholesterol synthesis leading to decreased cell membrane integrity
Explicação
Niemann-Pick disease type C is caused by mutations in NPC1 or NPC2, which encode proteins required for cholesterol movement from late endosomes/lysosomes. This causes cholesterol sequestration in these organelles, impairing SREBP-2 signaling and causing hepato... Ver explicação completa e trilha adaptativa →