Yukina Marina, Nuralieva Nurana, Sorkina Ekaterina, Troshina Ekaterina, Tiulpakov Anatoly, Belaya Zhanna, Melnichenko Galina
Endocrinology Research CentreMoscow, Russia.
Endocrinol Diabetes Metab Case Rep. 2021 Apr 14;2021. doi: 10.1530/EDM-20-0188.
Lamin A/C (LMNA) gene mutations cause a heterogeneous group of progeroid disorders, including Hutchinson-Gilford progeria syndrome, mandibuloacral dysplasia, atypical progeroid syndrome (APS) and generalized lipodystrophy-associated progeroid syndrome (GLPS). All of those syndromes are associated with some progeroid features, lipodystrophy and metabolic complications but vary differently depending on a particular mutation and even patients carrying the same gene variant are known to have clinical heterogeneity. We report a new 30-year-old female patient from Russia with an APS and generalized lipodystrophy (GL) due to the heterozygous de novo LMNA p.E262K mutation and compare her clinical and metabolic features to those of other described patients with APS. Despite many health issues, short stature, skeletal problems, GL and late diagnosis of APS, our patient seems to be relatively metabolically healthy for her age when compared to previously described patients with APS.
Atypical progeroid syndromes (APS) are rare and heterogenic with different age of onset and degree of metabolic disorders, which makes this diagnosis very challenging for clinicians and may be missed until the adulthood. The clinical picture of the APS depends on a particular mutation in the LMNA gene, but may vary even between the patients with the same mutation. The APS due to a heterozygous LMNA p.E262K mutation, which we report in this patient, seems to have association with the generalized lipodystrophy, short stature and osteoporosis, but otherwise, it seems to cause relatively mild metabolic complications by the age of 30. The patients with APS and lipodystrophy syndromes require a personalized and multidisciplinary approach, and so they should be referred to highly specialized reference-centres for diagnostics and treatment as early as possible. Because of the high heterogeneity of such a rare disease as APS, every patient's description is noteworthy for a better understanding of this challenging syndrome, including the analysis of genotype-phenotype correlations.
核纤层蛋白A/C（LMNA）基因突变会导致一组异质性的早老症候群，包括哈钦森-吉尔福德早衰综合征、下颌-肢端发育异常、非典型早老症候群（APS）以及与全身性脂肪营养不良相关的早老症候群（GLPS）。所有这些综合征都与一些早老特征、脂肪营养不良和代谢并发症相关，但因特定突变而有所不同，甚至已知携带相同基因变异的患者也存在临床异质性。我们报告了一名来自俄罗斯的30岁女性患者，她因杂合性新发LMNA p.E262K突变而患有APS和全身性脂肪营养不良（GL），并将她的临床和代谢特征与其他已描述的APS患者进行了比较。尽管存在许多健康问题、身材矮小、骨骼问题、GL以及APS的晚期诊断，但与先前描述的APS患者相比，我们的患者在其年龄阶段似乎代谢相对健康。
非典型早老症候群（APS）罕见且具有异质性，发病年龄和代谢紊乱程度各不相同，这使得临床医生做出诊断极具挑战性，且可能直到成年才被发现。APS的临床表现取决于LMNA基因中的特定突变，但即使是具有相同突变的患者之间也可能存在差异。我们在该患者中报告的由杂合性LMNA p.E262K突变引起的APS似乎与全身性脂肪营养不良、身材矮小和骨质疏松有关，但在30岁时，除此之外，它似乎仅引起相对较轻的代谢并发症。患有APS和脂肪营养不良综合征的患者需要个性化的多学科方法，因此应尽早转诊至高度专业化的参考中心进行诊断和治疗。由于APS这种罕见疾病具有高度异质性，每例患者的描述对于更好地理解这一具有挑战性的综合征都很有价值，包括对基因型-表型相关性的分析。
