Department of Medical Genetics, Osaka Women's and Children's Hospital, Izumi 594-1101, Japan.
Department of Molecular Medicine, Research Institute, Osaka Women's and Children's Hospital, Izumi 594-1101, Japan.
Cells. 2021 Nov 10;10(11):3117. doi: 10.3390/cells10113117.
Congenital disorders of glycosylation (CDG), inherited metabolic diseases caused by defects in glycosylation, are characterized by a high frequency of intellectual disability (ID) and various clinical manifestations. Two siblings with ID, dysmorphic features, and epilepsy were examined using mass spectrometry of serum transferrin, which revealed a CDG type 2 pattern. Whole-exome sequencing showed that both patients were homozygous for a novel pathogenic variant of (NM_016219.4:c.1837del) inherited from their healthy parents. We conducted a HPLC analysis of sialylated N-linked glycans released from total plasma proteins and characterized the α1,2-mannosidase I activity of the lymphocyte microsome fraction. The accumulation of monosialoglycans was observed in MAN1B1-deficient patients, indicating N-glycan-processing defects. The enzymatic activity of MAN1B1 was compromised in patient-derived lymphocytes. The present patients exhibited unique manifestations including early-onset epileptic encephalopathy and cerebral infarction. They also showed coagulation abnormalities and hypertransaminasemia. Neither sibling had truncal obesity, which is one of the characteristic features of MAN1B1-CDG.
先天性糖基化障碍（CDG）是一种由糖基化缺陷引起的遗传性代谢疾病，其特征是智力残疾（ID）和各种临床表现的发病率较高。两名患有 ID、发育异常和癫痫的兄弟姐妹接受了血清转铁蛋白的质谱分析，结果显示为 CDG 2 型模式。全外显子组测序显示，两名患者均携带来自健康父母的新型致病性变异（NM_016219.4：c.1837del）纯合子。我们对从总血浆蛋白中释放的唾液酸化 N-连接糖进行了 HPLC 分析，并对淋巴细胞微粒体部分的α1,2-甘露糖苷酶 I 活性进行了表征。在 MAN1B1 缺陷患者中观察到单唾液酸化糖的积累，表明存在 N-聚糖加工缺陷。患者来源的淋巴细胞中 MAN1B1 的酶活性受损。本研究中的患者表现出独特的临床表现，包括早发性癫痫性脑病和脑梗死。他们还表现出凝血异常和高转氨酶血症。这两兄弟均无躯干肥胖，这是 MAN1B1-CDG 的特征之一。
