CONTEXT: A heterozygous missense mutation substituting arginine at position 133 to leucine in the lamin A/C protein has been reported in two young women with clinical features of short stature, bird-like faces, and early onset of aging processes. OBJECTIVE: The objective of the study was to carry out detailed phenotyping of these two women by evaluating the pattern of fat loss using anthropometry, dual-energy x-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI) and study metabolic abnormalities in glucose and lipid metabolism. DESIGN: The study consisted of descriptive case reports. SETTING: The study was conducted at a referral center. PATIENTS: Patient 1 was a 23-yr-old African-American female with progeroid features. Patient 2 was a 24-yr-old Caucasian female with generalized lipodystrophy, hypertriglyceridemia, and severe insulin resistance diabetes who required more than 200 U of insulin daily. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: Body fat distribution to characterize pattern of lipodystrophy and nuclear morphology abnormalities in skin fibroblasts were studied. RESULTS: Patient 1 had normal body fat (27%) by DEXA. However, MRI revealed relative paucity of sc fat in the distal extremities, with preservation of sc truncal fat. She had impaired glucose tolerance and elevated postprandial serum insulin levels. Patient 2, in contrast, had only 11.6% body fat as determined by DEXA and had generalized loss of sc and intraabdominal fat on MRI. Skin fibroblasts from patient 2 showed marked abnormal nuclear morphology, compared with those from patient 1. Despite the deranged nuclear morphology, the lamin A/C remained localized to the nuclear envelope, and the nuclear DNA remained within the nucleus. CONCLUSIONS: Atypical Werner's syndrome associated with Arg133Leu mutation in the LMNA gene presents with a phenotypically heterogeneous disorder. Furthermore, the severity of metabolic complications seems to correlate with the extent of lipodystrophy.
CONTEXT: A heterozygous missense mutation substituting arginine at position 133 to leucine in the lamin A/C protein has been reported in two young women with clinical features of short stature, bird-like faces, and early onset of aging processes. OBJECTIVE: The objective of the study was to carry out detailed phenotyping of these two women by evaluating the pattern of fat loss using anthropometry, dual-energy x-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI) and study metabolic abnormalities in glucose and lipid metabolism. DESIGN: The study consisted of descriptive case reports. SETTING: The study was conducted at a referral center. PATIENTS: Patient 1 was a 23-yr-old African-American female with progeroid features. Patient 2 was a 24-yr-old Caucasian female with generalized lipodystrophy, hypertriglyceridemia, and severe insulin resistance diabetes who required more than 200 U of insulin daily. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: Body fat distribution to characterize pattern of lipodystrophy and nuclear morphology abnormalities in skin fibroblasts were studied. RESULTS:Patient 1 had normal body fat (27%) by DEXA. However, MRI revealed relative paucity of sc fat in the distal extremities, with preservation of sc truncal fat. She had impaired glucose tolerance and elevated postprandial serum insulin levels. Patient 2, in contrast, had only 11.6% body fat as determined by DEXA and had generalized loss of sc and intraabdominal fat on MRI. Skin fibroblasts from patient 2 showed marked abnormal nuclear morphology, compared with those from patient 1. Despite the deranged nuclear morphology, the lamin A/C remained localized to the nuclear envelope, and the nuclear DNA remained within the nucleus. CONCLUSIONS: Atypical Werner's syndrome associated with Arg133Leu mutation in the LMNA gene presents with a phenotypically heterogeneous disorder. Furthermore, the severity of metabolic complications seems to correlate with the extent of lipodystrophy.
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