👤 Baran A Ersoy

The combination of acute pancreatitis (AP), severe hypertriglyceridemia (HTG), and diabetic ketoacidosis (DKA) poses a life-threatening triad. Although DKA is a frequent complication in children, this triad is rare. We report a 10-year-old girl with type 1 diabetes mellitus (T1DM) for 10 months, who presented with DKA, severe HTG, and AP. Her serum was lipemic. She had HTG (1733 mg/dl, 19.5 mmol/L; reference range, 90-129 mg/dl, 1,016-1,456 mmol/L) and severe abdominal pain that did not improve despite treatment for ketoacidosis. She had high lipase levels (1581 U/L, reference range 28-100 U/L), and pancreatitis was detected on abdominal tomography. She recovered with a combination of hydration and insulin therapy. A heterozygous p.N318S (c.953A>G) variant was detected in her lipoprotein lipase (LPL) gene. Her apolipoprotein B (ApoB) was elevated at 1.44 g/L (reference range, 0.6-1.17 g/L, 60-117 mg/dl). It is well established that both the likely pathogenic LPL variants and high ApoB concentrations contribute to an increased risk of cardiovascular complications. Therefore, it is recommended to evaluate for a pathogenic variant in the LPL gene in children with T1DM who do not have dyslipidemia but exhibit the rare triad of AP, HTG, and DKA. Show less

Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans Show less

Genetic variants in genes encoding components of lipid metabolism have been associated with AMD. The aims of this study were to evaluate the relation of these genetic variants with serum lipid levels in AMD in a large case-control cohort (n = 3070) and to test for correlations between lipids and complement activation. Single nucleotide polymorphisms (SNPs) in eight lipid metabolism genes, previously described to be associated with AMD, were genotyped and tested for their association in our case-control cohort. Serum apolipoprotein B (ApoB), apolipoprotein AI (Apo-AI), cholesterol, triglycerides (TG), high-density lipoprotein-cholesterol (HDLC), and complement activation levels (C3d/C3) were measured and tested for association with AMD. Non-HDL cholesterol and LDL were inferred based on the measurements of the other lipids and lipoproteins. General linear models and χ2 tests were used to evaluate the relation of SNPs and lipids/lipoproteins to the disease as well as their interrelations. Significant genotypic associations with AMD were observed for SNPs in CETP, APOE, and FADS1. The serum levels of Apo-AI and HDLC were significantly higher in patients compared with controls. Triglycerides (TG) levels were lower in AMD compared with controls. A cumulative effect was observed for APOE and CETP genotypes on HDLC and Apo-AI levels. Complement activation levels correlated positively with HDLC and Apo-AI, and negatively with TG. Both the lipids/lipoproteins and the complement activation levels associate independently to AMD. This study bridges the gap between genetic associations and physiological lipid levels in AMD. Additionally, the observed correlations between complement activation and lipid levels link two major systems that previously were always assessed independently. Show less