VARIABLE EXPRESSION OF FAMILIAL HETEROZYGOUS HYPOBETALIPOPROTEINEMIA - TRANSIENT MALABSORPTION DURING INFANCY

Rare instances of symptomatic fat malabsorption have been reported in patients with heterozygous hypobetalipoproteinemia, but with an unclea r pathogenesis. An 8-month-old boy with chronic diarrhea and failure t o thrive was found to have abnormally low plasma total cholesterol (85 mg/dl), LDL-cholesterol (48 mg/dl), apoB (52 mg/dl), apoA-I(53 mg/dl) , and Vitamin E (0.22 mg/dl). Decreased plasma LDL-C and apoB were not ed in the father (34 and 40 mg/dl, respectively), as well as several o ther family members. Fasting triglycerides were normal but did not inc rease normally in response to a fat meal test. Lipoprotein composition showed an abnormal profile of very low density (VLDL, d 1.006 g/ml), low density (LDL, d 1.063 g/ml), and high density (HDL, d 1.21 g/ml) l ipoproteins. A fasting jejunal biopsy revealed lipid-laden enterocytes . Electron microscopy of the jejunal biopsy revealed the absence of li pid particles in the intercellular-spaces-after a fat meal. Jejunal ex plants cultured with [C-14]palmitate and [H-3]leucine showed limited s ynthesis of triglycerides and apolipoproteins (36 and 42% of controls, respectively), whereas the father's results were close to normal. At 1 year of age, improvement in intestinal fat absorption was accompanie d by the presence of chylomicrons in the intercellular space, concomit ant with the enhanced synthesis of lipids and apoB by jejunal explants . These data provide evidence that heterozygous hypobetalipoproteinemi a may present early in life as transient, symptomatic lipid malabsorpt ion. The mechanisms responsible for improved lipid transport despite p ersistent hypobetalipoproteinemia remain to be established.