Ding Si, Deng Yuxin, Hao Lili, Qiu Wenjuan, Wu Shengnan, Chen Yongxing, Chen Ting, Zhan Xia, Han Lianshu, Jiao Xianting
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai, 200092, China.
Department of Endocrinology and Genetic Metabolism, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, Henan, 400052, China.
Orphanet J Rare Dis. 2025 Jun 4;20(1):276. doi: 10.1186/s13023-025-03839-5.
Pulmonary Hypertension (PH) in patients with cblC deficiency is one of the rare but lethal complications. This study aimed to described its characteristics and long-term outcome.
A total of 26 patients with cblC deficiency complicated by PH were enrolled. Clinical and laboratory data were reviewed in detail.
Sixteen patients presented with PH manifestations as the initial symptom while ten patients developed PH after the involvement of other systems. The median onset age of PH was 3.25 years (ranging from 1 month to 13.4 years). Sixteen cases had other cardiovascular damage, including right cardiac enlargement, atrial septal defects, ventricular septal defects, left ventricular hypertrophy, pericardial effusion, pulmonary artery fistula and mild pulmonary artery stenosis. Intramuscular hydroxylcobalamin was given to all patients, together with L-carnitine, betaine and folinic acid after diagnosis. And PH targeted drags were given to 12 cases. As a result, propionylcarnitine, propionylcarnitine/acetylcarnitine ratio, methylmalonic acid, methylcitric acid and homocysteine levels decreased while methionine levels increased remarkably after treatment(p<0.05). The c.80 A> G variant was the most frequent allele in this cohort. Pulmonary artery systolic pressure was within the normal range in all patients, except that one case still had PH and two cases died. Multi-system involvement was improved overall.
cblC deficiency should be considered in patients with PH. Multi-system evaluation, especially echocardiography is recommended to be performed regularly at each patient visit. The c.80 A > G variant might be a hot-spot mutation of cblC deficiency complicated with PH. Most patients show optimistic prognosis, while neurological damage is usually difficult to reverse.
cblC 缺乏症患者的肺动脉高压（PH）是一种罕见但致命的并发症。本研究旨在描述其特征和长期预后。
共纳入 26 例合并 PH 的 cblC 缺乏症患者。详细回顾临床和实验室数据。
16 例患者以 PH 表现为首发症状，10 例患者在其他系统受累后出现 PH。PH 的中位发病年龄为 3.25 岁（范围为 1 个月至 13.4 岁）。16 例有其他心血管损害，包括右心扩大、房间隔缺损、室间隔缺损、左心室肥厚、心包积液、肺动脉瘘和轻度肺动脉狭窄。所有患者诊断后均给予肌肉注射羟钴胺素，同时给予左卡尼汀、甜菜碱和亚叶酸。12 例给予 PH 靶向药物。结果，治疗后丙酰肉碱、丙酰肉碱/乙酰肉碱比值、甲基丙二酸、甲基柠檬酸和同型半胱氨酸水平降低，而蛋氨酸水平显著升高（p<0.05）。c.80 A>G 变异是该队列中最常见的等位基因。除 1 例仍有 PH 和 2 例死亡外，所有患者的肺动脉收缩压均在正常范围内。多系统受累总体有所改善。
PH 患者应考虑 cblC 缺乏症。建议每次就诊时对每位患者进行多系统评估，尤其是超声心动图检查。c.80 A>G 变异可能是 cblC 缺乏症合并 PH 的热点突变。大多数患者预后乐观，而神经损伤通常难以逆转。
