a Assistance Publique-Hôpitaux de Paris (AP-HP) , Hôpital Saint-Antoine, Centre de Référence des Pathologies Rares de l'Insulino-Sécrétion et de l'Insulino-Sensibilité (PRISIS), Service d'Endocrinologie, Diabétologie et Endocrinologie de la Reproduction , Paris , France.
b Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine , Institut Hospitalo-Universitaire de Cardio-métabolisme et Nutrition (ICAN) , Paris , France.
Curr Med Res Opin. 2019 Mar;35(3):543-552. doi: 10.1080/03007995.2018.1533459. Epub 2018 Nov 9.
Lipodystrophic syndromes are rare diseases of genetic or acquired origin characterized by partial or generalized lack of body fat. Early detection and diagnosis are crucial to prevent and manage associated metabolic dysfunctions, i.e. insulin resistance, dyslipidemia, fatty liver, and diabetes, and to provide appropriate genetic counseling. By means of several representative case studies, this article illustrates the diagnostic and management challenges of lipodystrophic syndromes.
Berardinelli-Seip congenital lipodystrophy (BSCL) is typically diagnosed at birth, or soon thereafter, with generalized lipoatrophy and hepatomegaly secondary to hepatic steatosis. Physicians must also consider this diagnosis in adults with atypical non-autoimmune diabetes, hypertriglyceridemia, and a lean and muscular phenotype. The BSCL1 subtype due to mutations in the AGPAT2 gene can have an unusual presentation, especially in neonates and infants. Particular attention should be paid to infants presenting failure to thrive who also have hepatomegaly and metabolic derangements. The BSCL2 sub-type due to mutations in the BSCL gene tends to be more severe than BSCL1, and is characterized by greater fat loss, mild intellectual disability, earlier onset of diabetes, and higher incidence of premature death. Effective management from an earlier age may moderate the natural disease course. Partial lipodystrophies may easily be confused with common central obesity and/or metabolic syndrome. In patients with unexplained pancreatitis and hypertriglyceridemia, lipodystrophies such as familial partial lipodystrophy type 2 (FPLD2; Dunnigan type, due to LMNA mutations) should be considered. Oral combined contraceptives, which can reveal the disease by inducing severe hypertriglyceridemia, are contraindicated. Endogenous estrogens may also lead to "unmasking" of the FPLD2 phenotype, which often appears at puberty, and is more severe in females than males.
Diet and exercise, adapted to age and potential comorbidities, are essential prerequisites for therapeutic management of lipodystrophic syndromes. Metreleptin therapy can be useful to manage lipodystrophy-related metabolic complications.
脂肪营养不良综合征是一种罕见的遗传性或获得性疾病，其特征为部分或全身性脂肪缺失。早期发现和诊断对于预防和管理相关代谢功能障碍（如胰岛素抵抗、血脂异常、脂肪肝和糖尿病）以及提供适当的遗传咨询至关重要。本文通过几个具有代表性的病例研究，说明了脂肪营养不良综合征的诊断和管理挑战。
先天性脂肪营养不良症（BSCL）通常在出生时或出生后不久被诊断，表现为全身性脂肪萎缩和肝肿大，继发于肝脂肪变性。医生还必须考虑到具有非自身免疫性糖尿病、高甘油三酯血症、消瘦和肌肉发达表型的成年人的这种诊断。由于 AGPAT2 基因突变引起的 BSCL1 亚型，尤其是在新生儿和婴儿中，可能表现出不典型的特征。特别需要注意的是，有肝肿大和代谢紊乱的生长不良的婴儿。由于 BSCL 基因突变引起的 BSCL2 亚型比 BSCL1 更严重，其特征是脂肪丢失更多、轻度智力障碍、糖尿病发病更早和过早死亡的发生率更高。更早开始有效管理可能会减轻自然病程。部分性脂肪营养不良症很容易与常见的中心性肥胖和/或代谢综合征相混淆。对于不明原因的胰腺炎和高甘油三酯血症患者，应考虑脂肪营养不良症，如家族性部分性脂肪营养不良 2 型（FPLD2；Dunnigan 型，由于 LMNA 突变）。口服联合避孕药可能会通过诱导严重的高甘油三酯血症而“揭示”该疾病，因此禁用。内源性雌激素也可能导致 FPLD2 表型的“显露”，这种表型通常在青春期出现，且女性比男性更严重。
饮食和运动是治疗脂肪营养不良综合征的必要前提，应根据年龄和潜在的合并症进行调整。米雷替康治疗可用于治疗脂肪营养不良相关的代谢并发症。
