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Variable expression of familial heterozygous hypobetalipoproteinemia: transient malabsorption during infancy
1Gastroenterology-Nutrition Research Unit, Hôpital Sainte-Justine, Québec, Canada.
Insights
Heterozygous hypobetalipoproteinemia can cause temporary fat malabsorption in infants, leading to failure to thrive. This condition improves over time, though the exact mechanisms require further study.
Area of Science:
- Biochemistry
- Gastroenterology
- Genetics
Background:
- Heterozygous hypobetalipoproteinemia (hHBL) is a genetic disorder characterized by low levels of beta-lipoprotein, typically asymptomatic.
- Rare cases of symptomatic fat malabsorption in hHBL suggest underlying complexities in lipid metabolism.
Observation:
- An 8-month-old infant presented with chronic diarrhea, failure to thrive, and significantly low plasma lipids and vitamin E.
- Family studies revealed low LDL-cholesterol (LDL-C) and apolipoprotein B (apoB) in the father and other relatives.
- Jejunal biopsy showed lipid-laden enterocytes and an absence of intercellular lipid particles post-fat load, indicating impaired intestinal lipid transport.
Findings:
- Infant's jejunal explants demonstrated reduced synthesis of triglycerides and apolipoproteins compared to controls.
- At one year, the infant showed improved fat absorption, with chylomicron presence in intercellular spaces and enhanced lipid/apoB synthesis.
- These findings suggest a transient defect in lipid transport and synthesis in early life associated with hHBL.
Implications:
- This study highlights that heterozygous hypobetalipoproteinemia can manifest as symptomatic, transient fat malabsorption in infancy.
- The observed improvement suggests potential compensatory mechanisms for lipid transport that warrant further investigation.
- Understanding these mechanisms could lead to targeted therapies for lipid malabsorption disorders.
Abstract:
Rare instances of symptomatic fat malabsorption have been reported in patients with heterozygous hypobetalipoproteinemia, but with an unclear pathogenesis. An 8-month-old boy with chronic diarrhea and failure to 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 noted in the father (34 and 40 mg/dl, respectively), as well as several other family members. Fasting triglycerides were normal but did not increase 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) lipoproteins. A fasting jejunal biopsy revealed lipid-laden enterocytes. Electron microscopy of the jejunal biopsy revealed the absence of lipid particles in the intercellular spaces after a fat meal. Jejunal explants cultured with [14C]palmitate and [3H]leucine showed limited synthesis 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 accompanied by the presence of chylomicrons in the intercellular space, concomitant with the enhanced synthesis of lipids and apoB by jejunal explants. These data provide evidence that heterozygous hypobetalipoproteinemia may present early in life as transient, symptomatic lipid malabsorption. The mechanisms responsible for improved lipid transport despite persistent hypobetalipoproteinemia remain to be established.