A 5-month-old boy is being evaluated for poor weight gain since birth. He is noted to have bulky and greasy stools. A jejunal biopsy shows the findings seen in the slide below. Which of the following is the most likely diagnosis?

Question

A 5-month-old boy is being evaluated for poor weight gain since birth.  He is noted to have bulky and greasy stools.  A jejunal biopsy shows the findings seen in the slide below.  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

11ec160b_3926_fbb9_9249_3908314eee0c_MD0001_00 The slide above shows normal intestinal mucosal architecture, but the enterocytes contain clear or foamy cytoplasm which is more prominent at the tips of the villi. These findings occur due to accumulation of lipids in the absorptive cells of the intestinal epithelium and are typical of abetalipoproteinemia, a disease caused by impaired formation of apolipoprotein B (apoB)-containing lipoproteins. Dietary lipids are normally processed in small-bowel enterocytes and secreted as chylomicrons; endogenously produced lipids are secreted from liver hepatocytes as very low-density lipoprotein (VLDL). Chylomicron and VLDL particles are synthesized within the endoplasmic reticulum as lipids accumulate around a single apoB molecule. ApoB-100 is found in VLDL, and apoB-48 (a truncated version without the LDL receptor ligand) is present in chylomicrons. During the synthesis of apoB-containing lipoproteins, microsomal triglyceride transfer protein (MTP) functions as a chaperone protein necessary for proper folding of apoB and also participates in the transfer of lipids to newly formed chylomicrons and VLDL particles. Abetalipoproteinemia is most commonly caused by an autosomal recessive, loss-of-function mutation in the MTP gene. It manifests during the first year of life with symptoms of malabsorption (eg, abdominal distention, foul-smelling stool). Laboratory studies show very low plasma triglyceride and cholesterol levels; chylomicrons, VLDLs, and apoB are entirely absent from the blood. Poor lipid absorption causes deficiency of fat-soluble vitamins (particularly vitamin E) and essential fatty acids. This results in red blood cells with abnormal membranes and thorny projections called acanthocytes as well as multiple neurologic abnormalities (eg, progressive ataxia, retinitis pigmentosa). (Choice B) Light microscopy shows atrophy and blunting of the villi in celiac disease. Chronic inflammatory infiltrate of the lamina propria is also present. These features are not seen in the slide above. (Choices C, E, and G) No abnormalities are found on light microscopy of the small intestine in chronic pancreatitis or lactase deficiency. In Zollinger-Ellison syndrome, the small intestine may show ulcerations due to gastrin production by a neuroendocrine tumor (ie, gastrinoma). (Choice D) Light microscopy in Crohn disease shows chronic inflammation of all layers of the intestinal wall and noncaseating granulomas. (Choice F) The characteristic microscopic finding in Whipple disease is distended macrophages in the lamina propria of the small intestine. Macrophages contain PAS-positive and diastase-resistant granules and rod-shaped Tropheryma whipplei bacilli. Educational objective: Abetalipoproteinemia is an inherited inability to synthesize apolipoprotein B, an important component of chylomicrons and very low-density lipoprotein. Lipids absorbed by the small intestine cannot be transported into the circulation and instead accumulate in the intestinal epithelium, resulting in enterocytes with clear or foamy cytoplasm.

A 5-Month-Old Boy Is Being Evaluated for Poor Weight Gain