A novel nutritional approach to infants and children with congenital diarrhea due to homozygous DGAT1 mutations.

OBJECTIVES: Diacylglycerol acyltransferase (DGAT) catalyzes the final step in triglyceride synthesis. DGAT1 is expressed in human enterocytes and is essential for fat absorption. Homozygous DGAT1 deficiency often presents with severe diarrhea and protein-losing enteropathy (PLE) in the 1st weeks of life. Because severe restriction of fat intake controls diarrhea and decreases PLE, total parenteral nutrition (TPN) was the initial standard therapy in infants and children. We present tertiary center experience managing infants and children with DGAT1 deficiency resulting in the development of a nutritional approach that minimizes the use of TPN. METHODS: From 2014 to 2020, 12 infants with DGAT1 deficiency were treated. Stool output, growth, and development, as well as essential fatty acid status, were monitored. This retrospective experience formed the basis for treatment recommendations, which include an ultralow fat formula with intermittent peripheral intravenous lipid infusions during the 1st year of life. RESULTS: All patients with prolonged intestinal fat exposure had PLE, which resolved when treated with the nutrition protocol. Essential fatty acid status as measured by triene:tetraene ratios normalized in all treated patients. Over time, early genetic diagnosis and prompt initiation of an ultralow fat diet with peripheral intravenous lipid infusions replaced the need for TPN. CONCLUSIONS: Children with DGAT1 deficiency respond to dietary restriction of lipids. Management with a novel nutritional approach provides effective treatment for infants with DGAT1 deficiency, treats diarrhea and PLE, promotes growth and development, avoids TPN dependency, and decreases the potential for essential fatty acid deficiency.

CFTR potentiator therapy ameliorates impaired insulin secretion in CF patients with a gating mutation.

OBJECTIVE: To investigate the effect of treatment with ivacaftor on insulin secretion in patients with cystic fibrosis (CF) (ΔF508\S549R) having CFRD/impaired insulin secretion. METHODS: A standard OGTT was performed before and after 16weeks of treatment with ivacaftor in 2 sibling patients with CF carrying the S549R gating mutation. The area under the curve (AUC) for glucose and insulin was calculated using the trapezoidal estimation. RESULTS: Before treatment, the OGTT of case 1 showed indeterminate glycemia; the OGTT of case 2 indicated CFRD. After ivacaftor treatment the OGTT demonstrated improved insulin secretion pattern mainly by increased first phase early insulin secretion, resulting in reduction of the AUC of glucose in both cases. CONCLUSIONS: The treatment with ivacaftor in patients with CF carrying gating mutation can ameliorate impaired insulin secretion. Further studies and larger cohorts are needed to evaluate the impact of ivacaftor on insulin secretion in patients with CF carrying gating or other mutations.