| Popis: |
FPLD2 is a rare autosomal dominant disorder characterized by loss of subcutaneous (sc) fat from the extremities but increased fat deposition in the face, neck and abdomen. Most FPLD2 patients (~75%) have “typical” heterozygous missense LMNA mutations affecting the arginine 482 residue and have severe loss of sc fat from the extremities and develop moderate to severe metabolic complications. Other patients have “atypical” mutations with variable loss of sc fat from the extremities and mild to severe metabolic complications. Since genetic testing is expensive, the diagnosis of FPLD2 is usually missed or delayed. Thus, there exists a need for an objective screening tool which can aid in the diagnosis of FPLD2. Therefore, we determined the predictive value of skinfold thickness measurements and various DEXA-based regional body fat parameters for diagnosis of FPLD2. We compared body fat data of 49 adult females (F) and 5 males (M) with FPLD2 to the sex- and age-matched controls (2,459 F, 3,459 M) from the National Health and Nutrition Examination Survey (NHANES) 2005-2010. Thirty nine patients had “typical” heterozygous p.R482W or p.R482Q LMNA mutation. The other heterozygous LMNA mutations included p.R582S (n = 1), p.R582H (n = 1), p.S583L (n = 3), p.R349W (n = 1), p.R25L (n = 1), p.G523R (n = 2), p.D192V (n = 1), p.L241P (n = 1), p.R62G (n = 2) and p.K515E (n = 2). The mean ± SD age and body mass index of affected F was 42 ± 13.5 y and 25.6 ± 4.5 kg/m2, respectively; and of affected M was 45.4 ± 11.6 y and 29.2 ± 7.0 kg/m2, respectively. Hypertriglyceridemia and diabetes mellitus were present in 74% and 52% of the FPLD2 patients, respectively. Our data revealed that the lower limb fat %, as well as the ratio of lower limb fat %/ truncal fat %, in all affected females were ≤ 1st percentile (%ile) of the controls, except in two patients, one of whom had a p.G523R mutation, and the other had a p.R482Q mutation but had an unusual excess fat accumulation in the medial part of the thighs and knees. All FPLD2 females had triceps skinfold thickness values ≤ 1st %ile of NHANES except in three patients. The subscapular skinfold thickness values in females on the other hand, were between the 5th to 99th %ile of NHANES. Unfortunately, data for thigh skinfold thickness were not available from NHANES. The lower limb fat % in affected males was below 25th %ile of controls. We conclude that DEXA-derived lower limb fat % and the ratio of lower limb fat %/ truncal fat % are the best predictors of FPLD2 diagnosis in females but not in males. Women with values of lower limb fat % (~ 20% or less) and the ratio of lower limb fat %/ truncal fat % (~ 0.85 or less), both of which are below the 1st %ile of NHANES data, should be further evaluated for diagnosis of FPLD2, especially if presenting with metabolic complications. |
