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 (> 885 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.
Highlights
Lipodystrophy refers to a heterogenous group of rare congenital or acquired metabolic disorders characterized by a complete or partial loss of adipose tissue.[1]
The heterozygous LMNA p.R482Q variant was seen in 51 patients (68.9%) while the p.R482W variant was seen in 23 patients (31.1%)
We found in our cohort of FPLD2 patients that the overall prevalence of severe HTG and hospitalization for acute pancreatitis was
Summary
Lipodystrophy refers to a heterogenous group of rare congenital or acquired metabolic disorders characterized by a complete or partial loss of adipose tissue.[1] Familial partial lipodystrophy (FPLD) is an inherited syndrome of body fat loss that is limited to certain regions.[1] The most common subtype, i.e. Dunnigan-type or FPLD2 (OMIM 151660), is caused by autosomal dominant pathogenic rare variants in the LMNA gene encoding lamin A/C.2. The FPLD2 clinical phenotype develops around puberty, with noticeable loss of subcutaneous fat in the extremities, trunk and gluteal region and a potential accumulation of fat in the face, neck, back, abdomen and labia majora. The core metabolic disturbance is insulin resistance. Many patients develop severe insulin resistance that can progress to frank diabetes mellitus termed "lipoatrophic diabetes", which increases the risk for microvascular and macrovascular complications. In some rare instances an overlap with arrhythmias or cardiomyopathy has been observed. 1 , 3
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