Department of Clinical Genomics, Mayo Clinic, Rochester, MN, United States of America; Division of Medical Genetics, Stanford University, CA, United States of America.
Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States of America.
Mol Genet Metab. 2023 Apr;138(4):107559. doi: 10.1016/j.ymgme.2023.107559. Epub 2023 Mar 17.
Phosphomannomutase-2-congenital disorder of glycosylation (PMM2-CDG) is the most common CDG and presents with highly variable features ranging from isolated neurologic involvement to severe multi-organ dysfunction. Liver abnormalities occur in in almost all patients and frequently include hepatomegaly and elevated aminotransferases, although only a minority of patients develop progressive hepatic fibrosis and liver failure. No curative therapies are currently available for PMM2-CDG, although investigation into several novel therapies is ongoing. We report the first successful liver transplantation in a 4-year-old patient with PMM2-CDG. Over a 3-year follow-up period, she demonstrated improved growth and neurocognitive development and complete normalization of liver enzymes, coagulation parameters, and carbohydrate-deficient transferrin profile, but persistently abnormal IgG glycosylation and recurrent upper airway infections that did not require hospitalization. Liver transplant should be considered as a treatment option for PMM2-CDG patients with end-stage liver disease, however these patients may be at increased risk for recurrent bacterial infections post-transplant.
磷酸甘露糖变位酶-2 型先天性糖基化障碍(PMM2-CDG)是最常见的 CDG 类型,表现出高度可变的特征,从孤立的神经系统受累到严重的多器官功能障碍不等。几乎所有患者均存在肝脏异常,常包括肝肿大和转氨酶升高,尽管只有少数患者发生进行性肝纤维化和肝功能衰竭。目前尚无针对 PMM2-CDG 的治愈疗法,尽管正在对几种新疗法进行研究。我们报告了首例成功的 PMM2-CDG 4 岁患者肝移植。在 3 年的随访期间,她的生长和神经认知发育得到改善,肝酶、凝血参数和糖基化转移蛋白谱完全正常化,但 IgG 糖基化持续异常和反复上呼吸道感染,无需住院治疗。对于终末期肝病的 PMM2-CDG 患者,肝移植应被视为一种治疗选择,然而这些患者在移植后可能有更高的复发性细菌感染风险。