Krawiec Paulina, Mełges Beata, Pac-Kożuchowska Elżbieta, Mroczkowska-Juchkiewicz Agnieszka, Czerska Kamila
Department of Paediatrics, Medical University of Lublin, Racławickie 1, 20-059, Lublin, Poland.
MEDGEN Medical Center, Orzycka 27, 02-695, Warsaw, Poland.
BMC Pediatr. 2016 Mar 14;16:38. doi: 10.1186/s12887-016-0581-2.
Familial partial lipodystrophy of the Dunnigan type (FPLD 2) is a rare autosomal dominant disorder caused by the mutations of the lamin A/C gene leading to the defective adipogenesis, premature death of adipocytes and lipotoxicity. FPLD 2 is characterized by a progressive loss of subcutaneous adipose tissue in the limbs and trunk, and accumulation of body fat in the face and neck with accompanying severe metabolic derangements including insulin resistance, glucose intolerance, diabetes, dyslipidemia, steatohepatitis. Clinical presentation of FPLD 2 can often lead to misdiagnosis with metabolic syndrome, type 2 diabetes or Cushing syndrome.
We report a case of a 14-year-old girl admitted to the Department of Paediatrics due to chronic hypertransaminasemia. On physical examination the girl appeared to have athletic posture. She demonstrated the absence of subcutaneous adipose tissue in the extremities, sparing the face, neck and gluteal area, pseudo-hypertrophy of calves, prominent peripheral veins of limbs, massive acanthosis nigricans around the neck, in axillary and inguinal regions and natural skin folds, hepatosplenomegaly. Laboratory results revealed hypertransaminasemia, elevated γ-glutamyltranspeptydase, and dyslipidemia, hyperinsulinaemia with insulin resistance, impaired glucose tolerance, and hyperuricemia. Diffuse steatoheptitis in the liver biopsy was stated. Clinical suspicion of FPLD 2 was confirmed genetically. The pathogenic mutation, R482W (p.Arg482Trp), responsible for the FPLD 2 phenotype was identified in one allele of the LMNA gene.
Presented case highlights the importance of the holistic approach to a patient and the need of accomplished collaboration between paediatricians and geneticists. FPLD 2 should be considered in the differential diagnosis of diabetes, dyslipidemia, steatohepatitis, acanthosis nigricans and polycystic ovary syndrome.
邓尼根型家族性部分脂肪营养不良（FPLD 2）是一种罕见的常染色体显性疾病，由核纤层蛋白A/C基因突变引起，导致脂肪生成缺陷、脂肪细胞过早死亡和脂毒性。FPLD 2的特征是四肢和躯干的皮下脂肪组织逐渐减少，面部和颈部脂肪堆积，并伴有严重的代谢紊乱，包括胰岛素抵抗、葡萄糖耐量异常、糖尿病、血脂异常、脂肪性肝炎。FPLD 2的临床表现常导致与代谢综合征、2型糖尿病或库欣综合征的误诊。
我们报告一例14岁女孩因慢性高转氨酶血症入住儿科。体格检查时，该女孩呈现运动员体态。她四肢无皮下脂肪组织，但面部、颈部和臀部除外，小腿假性肥大，四肢外周静脉明显，颈部、腋窝和腹股沟区域及自然皮肤褶皱处有大量黑棘皮病，肝脾肿大。实验室检查结果显示高转氨酶血症、γ-谷氨酰转肽酶升高、血脂异常、胰岛素抵抗伴高胰岛素血症、葡萄糖耐量受损和高尿酸血症。肝脏活检显示弥漫性脂肪性肝炎。FPLD 2的临床怀疑经基因检测得到证实。在核纤层蛋白A/C基因（LMNA）的一个等位基因中鉴定出导致FPLD 2表型的致病突变R482W（p.Arg482Trp）。
该病例突出了对患者采取整体治疗方法的重要性以及儿科医生和遗传学家之间充分合作的必要性。在糖尿病、血脂异常、脂肪性肝炎、黑棘皮病和多囊卵巢综合征的鉴别诊断中应考虑FPLD 2。
