LMNA gene mutation as a model of cardiometabolic dysfunction: from genetic analysis to treatment response.
OBJECTIVE
This report highlights the metabolic, endocrine and cardiovascular comorbidities in a case of familial partial lipodystrophy (FPLD), and also evaluates the efficacy and safety of metformin therapy.


METHODS
Mutational analysis was carried out of the LMNA gene in a teenage girl with an FPLD phenotype. Insulin resistance, sex hormones and metabolic parameters were also evaluated, and echocardiography, electrocardiography and 24-h blood pressure monitoring were also done.


RESULTS
The patient showed atypical fat distribution, insulin resistance and hypertrophic cardiomyopathy. Physical examination revealed muscle hypertrophy with a paucity of fat in the extremities, trunk and gluteal regions, yet excess fat deposits in the face, neck and dorsal cervical region. LMNA sequencing revealed a heterozygous missense mutation (c.1543A>G) in exon 9, leading to substitution of lysine by glutamic acid at position 515 (K515E). Moderate hypertension and secondary polycystic ovary syndrome were also assessed. Treatment with metformin resulted in progressive improvement of metabolic status, while blood pressure values normalized with atenolol therapy.


CONCLUSIONS
Very rapid and good results with no side-effects were achieved with metformin therapy for FPLD. The association of an unusual mutation in the LMNA gene was also described.
Department of Pediatric Sciences, University of Messina, Messina, Italy. Electronic address: valeriachirico@hotmail.it.
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Chirico
Department of Pediatric Sciences, University of Messina, Messina, Italy.
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Ferraù
Department of Pediatric Sciences, University of Messina, Messina, Italy.
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Loddo
Department of Pediatric Sciences, University of Messina, Messina, Italy.
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Briuglia
Department of Pediatric Sciences, University of Messina, Messina, Italy.
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Amorini
Department of Pediatric Sciences, University of Messina, Messina, Italy.
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Salpietro
Department of Internal Medicine, University of Messina, Messina, Italy; Department of Internal Medicine, Mediterranean Institute for Transplantation and Advanced Specialized Therapies, ISMETT, University of Pittsburgh Medical Center, Palermo, Italy.
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Lacquaniti
Department of Pediatric Sciences, University of Messina, Messina, Italy.
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Salpietro
Department of Pediatric Sciences, University of Messina, Messina, Italy.
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Arrigo
D000293:Adolescent; D000568:Amenorrhea / Q000188:drug therapy / Q000235:genetics*; D050218:Body Fat Distribution; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance; D034904:Lamin Type A / Q000235:genetics* / Q000378:metabolism; D052496:Lipodystrophy, Familial Partial / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008687:Metformin / Q000627:therapeutic use; D020125:Mutation, Missense; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; C494847:LMNA protein, human; D034904:Lamin Type A; D008687:Metformin
Amenorrhoea; FPLD; Familial partial lipodystrophy; Hyperinsulinism; Metabolic syndrome; Polycystic ovarian syndrome