HYPOGAMMAGLOBULINEMIA AS A PRESENTING FINDING OF DGAT1 DEFICIENCY

Abstract

<h3>Introduction</h3> The constellation of failure to thrive, chronic intractable diarrhea, and hypogammaglobulinemia should prompt the clinician to consider inborn errors of immunity (IEI), including defects in cellular and humoral immunity, immune dysregulatory disorders, and autoinflammatory disorders. However, the differential diagnosis should remain broad to include secondary causes of hypogammaglobulinemia, such as congenital diarrhea and enteropathies (CODEs). <h3>Case Description</h3> A two-week-old, full-term male presented with persistent diarrhea and failure to thrive. Endoscopic evaluation of the bowel showed active duodenitis and active colitis. Food protein-induced enterocolitis syndrome (FPIES) was considered due to transient improvement in stool output on an elemental formula; however, diarrhea recurred after advancing enteral feeds. Newborn screen was normal. Laboratory evaluation showed normal lymphocyte subpopulations, hypogammaglobulinemia (IgG < 108 mg/dL with normal IgA, IgM, IgE), hypoalbuminemia, and an elevated stool alpha-1 antitrypsin. Genetic testing revealed a compound heterozygous mutation in DGAT1 (c.1183C>T, c.329+6T>G). He received two doses of intravenous immunoglobulin; however, the stool output and IgG level resolved after starting a low-fat elemental formula. The patient remains on a low-fat diet with normal growth parameters and no recurrent infections with a normal IgG level. <h3>Discussion</h3> DGAT1 (diacylglycerol acyltransferase 1) deficiency is a protein-losing enteropathy due to defective lipid metabolism that is treated with a low-fat diet. Protein-losing conditions can cause hypoalbuminemia and hypogammaglobulinemia due to enteral loss of plasma proteins. It is important for clinicians to consider both primary hypogammaglobulinemia due to IEI and other conditions associated with secondary hypogammaglobulinemia when evaluating a patient with hypogammaglobulinemia.