Melikyan M A, Ivannikova T E, Milovanova N V, Kolodkina A A, Bezlepkina O B, Mokryshevа N G
Endocrinology Research Centre.
Research Centre for medical genetics.
Probl Endokrinol (Mosk). 2022 Jun 22;68(5):79-86. doi: 10.14341/probl13121.
Donohue syndrome (DS), also called Leprechaunism, is the most severe form of insulin resistance associated with biallelic mutations in INSR gene (OMIM: 147670). The approximate incidence of this syndrome is 1 per 1000000 births. Patients are present with typical clinical features such as intrauterine growth retardation, facial dysmorphism, severe metabolic disturbances, hepatomegaly and hypertrophic cardiomyopathy. Most DS patients die within the first two years of life due to respiratory infections, severe hypoglycemia or progressive cardiomyopathy. Treatment options are limited and no specific therapy exist for DS. Given the similarities between insulin and insulin-like growth factor 1 (IGF-1) receptors, recombinant human IGF-1 (rhIGF-1) has been used to treat severe insulin resistance including DS.We report the case of a male patient with genetically confirmed Donohue syndrome, successfully treated with continuous subcutaneous IGF1 infusion via insulin pump. We observed improvement of glycemic control, liver function and cardiac hypertrophy regression following 15-month IGF1 therapy.
多诺霍综合征（DS），也称为妖精貌综合征，是与胰岛素受体基因（OMIM：147670）双等位基因突变相关的最严重形式的胰岛素抵抗。该综合征的发病率约为每100万例出生中有1例。患者表现出典型的临床特征，如宫内生长迟缓、面部畸形、严重的代谢紊乱、肝肿大和肥厚性心肌病。大多数DS患者在生命的头两年内死于呼吸道感染、严重低血糖或进行性心肌病。治疗选择有限，目前尚无针对DS的特异性疗法。鉴于胰岛素和胰岛素样生长因子1（IGF-1）受体之间的相似性，重组人生长因子1（rhIGF-1）已被用于治疗包括DS在内的严重胰岛素抵抗。我们报告了一例经基因确诊的多诺霍综合征男性患者，通过胰岛素泵持续皮下输注IGF-1成功治疗。在15个月的IGF-1治疗后，我们观察到血糖控制得到改善、肝功能改善以及心脏肥大消退。
