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A 18-year-old man presents for a health maintenance examination. He has a family history of Tangier disease, and a number of adults in his family have either hepatosplenomegaly, recurrent polyneuropathy, or both. Which of the following
would be the strongest finding on physical examination to suggest the presence of this disease?

A. Angiokeratomas
B. Grey-brown pigmentation of the forehead, hands, and pre-tibial region
C. Irregular black deposits of clumped pigment in the peripheral retina
D. Orange-yellow tonsillar hyperplasia
E. Pingueculae

D ?

D...

The correct answer is D. Tangier disease is a rare familial disorder characterized by alpha-lipoprotein deficiency, which leads to very low high-density lipoprotein (HDL), recurrent polyneuropathy, lymphadenopathy, and hepatosplenomegaly due to storage of cholesterol esters in reticuloendothelial cells. Although you may never see this disease, the association of orange-yellow tonsillar hyperplasia (due to the cholesterol ester deposition there as well) with Tangier disease is a sufficiently distinctive clue in physical diagnosis to be worth remembering. (One rule of thumb in medicine is that although you will probably never see most of the very rare diseases, you will almost certainly see some of them.)
The presence of multiple angiokeratomas (choice A) on the lower half of the body suggests Fabry disease.
Grey-brown pigmentation of the forehead, hands, and pre-tibial region (choice B) suggests Gaucher disease.
Irregular black deposits of clumped pigment in the peripheral retina (choice C) are characteristic of retinitis pigmentosa, which may occur in association with abetalipoproteinemia and Refsum disease.
Pingueculae (choice E) could suggest Gaucher disease, but this could also occur in normal adults.