Kim Ja Hye, Kim Dohyung, Hwang Soojin, Kim Gu-Hwan, Lee Beom Hee, Yoo Han-Wook, Choi Jin-Ho
Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Medical Genetics Center, Asan Medical Cente, University of Ulsan College of Medicine, Seoul, Korea.
Orphanet J Rare Dis. 2025 May 17;20(1):235. doi: 10.1186/s13023-025-03773-6.
Endocrine dysfunctions are commonly associated with mitochondrial diseases. This study aimed to investigate clinical characteristics and outcomes of endocrine manifestations in patients with mitochondrial diseases.
This study included 54 patients from 47 families with mitochondrial diseases who were genetically confirmed; 49 patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), four with Pearson syndrome, and one with Kearns-Sayre syndrome (KSS). Clinical and endocrine findings were retrospectively reviewed.
The median age at diagnosis was 18.5 years (range, 0.1 - 49 years). In 49 patients with MELAS, the mean height and weight standard deviation scores were - 2.0 ± 1.3 and - 2.6 ± 1.6, respectively, with 44.9% (n = 22) of the patients exhibiting short stature at diagnosis. Twenty-three (46.9%) patients with MELAS were diagnosed with diabetes mellitus (DM) at a median age of 26 years (range, 12 - 50 years). Interestingly, papillary thyroid cancer was observed in 10.2% of patients (n = 5) with MELAS at a mean age of 34.1 ± 6.9 years. One patient with MELAS and one with KSS exhibited hypoparathyroidism. Patients with Pearson syndrome and KSS exhibited more severe short stature. Adrenal insufficiency was noted in 50% of the patients with Pearson syndrome.
In 20% of patients with MELAS, endocrine dysfunctions including having a short stature, DM, and hypoparathyroidism preceded the onset of neurological manifestations. Papillary thyroid cancer occurred in 10% of patients with MELAS. Patients with Pearson syndrome and KSS showed profound growth retardation and multisystem dysfunctions, such as chronic kidney disease and neurological defects, which contributed to increased mortality.
内分泌功能障碍常与线粒体疾病相关。本研究旨在调查线粒体疾病患者内分泌表现的临床特征及预后。
本研究纳入了47个线粒体疾病家族的54例经基因确诊的患者；其中49例为线粒体脑肌病伴乳酸酸中毒及卒中样发作（MELAS），4例为皮尔逊综合征，1例为慢性进行性眼外肌麻痹（KSS）。对临床和内分泌学检查结果进行回顾性分析。
诊断时的中位年龄为18.5岁（范围0.1 - 49岁）。49例MELAS患者中，身高和体重标准差评分均值分别为 - 2.0±1.3和 - 2.6±1.6，44.9%（n = 22）的患者在诊断时身材矮小。23例（46.9%）MELAS患者在中位年龄26岁（范围12 - 50岁）时被诊断为糖尿病（DM）。有趣的是，10.2%（n = 5）的MELAS患者在平均年龄34.1±6.9岁时被发现患有甲状腺乳头状癌。1例MELAS患者和1例KSS患者出现甲状旁腺功能减退。皮尔逊综合征和KSS患者身材矮小更为严重。50%的皮尔逊综合征患者存在肾上腺功能不全。
20%的MELAS患者在神经学表现出现之前就存在包括身材矮小、糖尿病和甲状旁腺功能减退在内的内分泌功能障碍。10%的MELAS患者发生了甲状腺乳头状癌。皮尔逊综合征和KSS患者表现出严重的生长发育迟缓及多系统功能障碍，如慢性肾病和神经缺陷，这导致死亡率增加。
