Abstract：
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.
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.
摘要：
脂肪营养不良综合征是罕见的遗传或获得性疾病，其特征是部分或全身缺乏身体脂肪。早期检测和诊断对于预防和管理相关的代谢功能障碍至关重要。即胰岛素抵抗，血脂异常,脂肪肝,糖尿病,并提供适当的遗传咨询。通过几个代表性的案例研究，本文阐述了脂肪营养不良综合征的诊断和治疗挑战.
Berardinelli-Seip先天性脂肪营养不良（BSCL）通常在出生时被诊断出来，或此后不久,伴有全身性脂肪萎缩和继发于肝性脂肪变性的肝肿大。医生还必须在患有非典型非自身免疫性糖尿病的成人中考虑这种诊断，高甘油三酯血症,和瘦瘦的肌肉表型。由于AGPAT2基因突变导致的BSCL1亚型可能具有不寻常的表现，尤其是新生儿和婴儿。应特别注意表现出无法茁壮成长的婴儿，他们也患有肝肿大和代谢紊乱。由于BSCL基因突变导致的BSCL2亚型往往比BSCL1更严重，并且以更大的脂肪损失为特征，轻度智力残疾,糖尿病的早期发病，过早死亡的发生率较高。从较早的年龄开始进行有效的管理可以减轻自然疾病的病程。部分脂肪营养不良可能容易与常见的中心性肥胖和/或代谢综合征混淆。在无法解释的胰腺炎和高甘油三酯血症患者中，脂肪营养不良，如家族性部分脂肪营养不良2型（FPLD2；邓尼根型，由于LMNA突变）应考虑。口服联合避孕药，它可以通过诱导严重的高甘油三酯血症来揭示疾病，是禁忌的。内源性雌激素也可能导致“揭开”FPLD2表型，经常出现在青春期，女性比男性更严重。
饮食和锻炼，适应年龄和潜在的合并症，是脂肪营养不良综合征治疗管理的必要先决条件。Metreleptin治疗可用于管理脂肪营养不良相关的代谢并发症。
Berardinelli-Seip先天性脂肪营养不良（BSCL）通常在出生时被诊断出来，或此后不久,伴有全身性脂肪萎缩和继发于肝性脂肪变性的肝肿大。医生还必须在患有非典型非自身免疫性糖尿病的成人中考虑这种诊断，高甘油三酯血症,和瘦瘦的肌肉表型。由于AGPAT2基因突变导致的BSCL1亚型可能具有不寻常的表现，尤其是新生儿和婴儿。应特别注意表现出无法茁壮成长的婴儿，他们也患有肝肿大和代谢紊乱。由于BSCL基因突变导致的BSCL2亚型往往比BSCL1更严重，并且以更大的脂肪损失为特征，轻度智力残疾,糖尿病的早期发病，过早死亡的发生率较高。从较早的年龄开始进行有效的管理可以减轻自然疾病的病程。部分脂肪营养不良可能容易与常见的中心性肥胖和/或代谢综合征混淆。在无法解释的胰腺炎和高甘油三酯血症患者中，脂肪营养不良，如家族性部分脂肪营养不良2型（FPLD2；邓尼根型，由于LMNA突变）应考虑。口服联合避孕药，它可以通过诱导严重的高甘油三酯血症来揭示疾病，是禁忌的。内源性雌激素也可能导致“揭开”FPLD2表型，经常出现在青春期，女性比男性更严重。
饮食和锻炼，适应年龄和潜在的合并症，是脂肪营养不良综合征治疗管理的必要先决条件。Metreleptin治疗可用于管理脂肪营养不良相关的代谢并发症。
