Jabbaripour Sarmadian Amirreza, Abdinia Babak, Seyed Toutounchi Kia, Saberi Mohammad, Eskandarzadeh Shabnam
Pediatric Health Research Center Tabriz University of Medical Sciences Tabriz Iran.
Tabriz USERN Office Universal Scientific Education and Research Network (USERN) Tabriz Iran.
Clin Case Rep. 2025 Sep 7;13(9):e70847. doi: 10.1002/ccr3.70847. eCollection 2025 Sep.
Congenital disorders of glycosylation (CDG) are a heterogeneous group of inherited metabolic diseases (IMD) characterized by defects in the synthesis and modification of glycoproteins and glycolipids. One of these disorders is ATP6AP1-CDG, a rare X-linked disease with approximately 30 cases reported so far. Symptoms associated with ATP6AP1-CDG include immunodeficiency, liver dysfunction, and neurological manifestations. This report presents the first case of ATP6AP1-CDG in Iran and the Middle East, in a 5-month-old male infant presenting with fever, vomiting, diarrhea, and poor feeding. The patient had a history of similar symptoms at three and 4 months and had been hospitalized with a diagnosis of gastrointestinal (GI) infection. In addition, he had a history of recurrent seizures, which first began at 45 days old, and was treated with phenobarbital. On physical examinations, the patient was lethargic, severely hypotonic with decreased primitive reflexes, and dehydrated with dry mucous membranes and white plaques of candidiasis. There was no tenderness, guarding, or hepatosplenomegaly in the abdominal examination. Laboratory blood tests were requested, which revealed leukocytosis and normal liver and kidney functions, with negative blood, urine, cerebrospinal fluid, and stool cultures for bacterial growth. Considering the history of recurrent infections, idiopathic seizures, suspected immunodeficiency in the patient's deceased sibling and parental consanguinity, primary immunodeficiency was suspected as a possible diagnosis for the patient. Therefore, a panel of immune function tests was requested, all of which were within the normal range. This panel consisted of IgM, IgG, IgA, B-Cell markers (CD19), T-Cell markers (CD3, CD4, and CD8), TRECs, NK-Cell markers (CD16 and CD56), LTT-PHA, LTT-BCG, and CH50. Furthermore, whole exome sequencing (WES) was requested, which revealed a novel hemizygous deletion in the ATP6AP1 gene (NM_001183.6), designated as c.111_116del; p.Ala40_Ala41del (chrX:153657133 TGGCGGC>T, hg19 assembly).
先天性糖基化障碍（CDG）是一组异质性遗传性代谢疾病（IMD），其特征在于糖蛋白和糖脂的合成与修饰存在缺陷。其中一种疾病是ATP6AP1 - CDG，这是一种罕见的X连锁疾病，迄今为止报告了约30例。与ATP6AP1 - CDG相关的症状包括免疫缺陷、肝功能障碍和神经学表现。本报告介绍了伊朗和中东地区首例ATP6AP1 - CDG病例，该病例为一名5个月大的男婴，出现发热、呕吐、腹泻和喂养困难。该患者在3个月和4个月时曾有类似症状病史，并因诊断为胃肠道（GI）感染而住院。此外，他有反复癫痫发作的病史，首次发作于45日龄，曾接受苯巴比妥治疗。体格检查时，患者嗜睡，严重肌张力减退，原始反射减弱，脱水，黏膜干燥并有念珠菌感染的白色斑块。腹部检查无压痛、肌紧张或肝脾肿大。进行了实验室血液检查，结果显示白细胞增多，肝肾功能正常，血液、尿液、脑脊液和粪便细菌培养均为阴性。考虑到患者反复感染的病史、特发性癫痫发作、其已故同胞疑似免疫缺陷以及父母近亲结婚，怀疑原发性免疫缺陷可能是该患者的诊断。因此，进行了一组免疫功能测试，所有结果均在正常范围内。该测试组包括IgM、IgG、IgA、B细胞标志物（CD19）、T细胞标志物（CD3、CD4和CD8）、TREC、NK细胞标志物（CD16和CD56）、LTT - PHA、LTT - BCG和CH50。此外，还进行了全外显子组测序（WES），结果显示ATP6AP1基因（NM_001183.6）存在一个新的半合子缺失，命名为c.111_116del；p.Ala40_Ala41del（chrX:153657133 TGGCGGC>T，hg19组装）。
