Prevalence of severe hypertriglyceridemia and pancreatitis in familial partial lipodystrophy type 2

Abstract

Familial partial lipodystrophy (FPLD) is a rare Mendelian condition listed in the differential diagnosis of severe hypertriglyceridemia (HTG) and pancreatitis. Here we determined the prevalence of severe HTG and pancreatitis among a cohort of 74 FPLD patients assessed in a lipid clinic. We studied lipid profiles from individuals with either of the two most common pathogenic monoallelic variants in LMNA , namely p.R482Q (N = 51) and p.R482W (N = 23). In total, 28 (37.8%) patients with a mean age of 41.8 ± 14.8 years had diabetes, while 46 (62.2%) patients with a mean age of 35.4 ± 19.4 years had no diabetes. Among patients with and without diabetes, median TG levels (interquartile range) were 2.73 (4.78) and 1.86 (1.66) mmol/L (242 [423] and 165 [147] mg/dL), respectively. Overall, 4 subjects (5.4%) had triglyceride levels > 10 mmol/L ( > 875 mg/dL), of whom 3 (4.1%) had a history of hospitalization for acute pancreatitis. All 4 patients with severe HTG had diabetes, i.e. 14.3% of those with diabetes. In contrast, FPLD2 patients without diabetes had only mild HTG, with no instances of severe HTG or pancreatitis. Thus, among this selected lipid clinic cohort with lipodystrophy, severe HTG and pancreatitis in FPLD2 are relatively common when diabetes is present.

Familial Partial Lipodystrophy—Literature Review and Report of a Novel Variant in PPARG Expanding the Spectrum of Disease-Causing Alterations in FPLD3

“…Most authors propose that the severity of lipid disturbances translates directly into body fat reduction, which is more pronounced in women. Moreover, Lazarte et al suggest that the risk of severe hypertriglyceridemia and consequent pancreatitis in FPLD2 depends on the co-occurrence of diabetes [32]. Our index patient and her mother also demonstrate severe hypertriglyceridemia with features of high cellular insulin resistance, which supports the findings of other studies.…”

Genetic determinants of pancreatitis: relevance in severe hypertriglyceridemia

“…Severe HTG has also been observed in individuals with familial partial lipodystrophy (FLPD) subtype 2 caused by pathogenic rare variants in LMNA (OMIM 150330) encoding nuclear lamin A/C [ 69 ]. In these patients, hypertriglyceridemia severity is typically mild-to-moderate.…”

“…In these patients, hypertriglyceridemia severity is typically mild-to-moderate. However, about 15% of patients experience sustained severe hypertriglyceridemia >10 mmol/l and this subgroup has a very high lifetime risk of acute pancreatitis, emphasizing again that irrespective of the genetic background, the proximal determinant of pancreatitis risk is the severity of the triglyceride elevation [ 69 ].…”

Advances in the care of lipodystrophies

“…An observational study by Lazarte et al [16 & ] in FPLD patients found that the risk of severe HTG and pancreatitis depends on the presence of diabetes mellitus. Study participants with diabetes had, on average, moderate HTG, with 14.3% having severe HTG and 10.7% a history of pancreatitis [16 ]. It is recommended that triglycerides be measured at least annually, and a fasting lipid panel at diagnosis and annually after 10 years of age in patients with lipodystrophies [4].…”