Austin Stephanie L, Chiou Andrew, Sun Baodong, Case Laura E, Govendrageloo Kenny, Hansen Perrin, Kishnani Priya S
Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Doctor of Physical Therapy Division, Duke University Medical Center, Durham, NC, USA.
Mol Genet Metab. 2017 Jan-Feb;120(1-2):96-100. doi: 10.1016/j.ymgme.2016.09.006. Epub 2016 Sep 28.
PRKAG2 syndrome, an autosomal dominant disorder, is characterized by severe infantile hypertrophic cardiomyopathy and heart rhythm disturbances to cases with a later presentation and a spectrum of manifestations including cardiac manifestations, myopathy and seizures. The cardiac features of PRKAG2 resemble the cardiac manifestations of Pompe disease. We present a patient who was initially diagnosed with Pompe disease and treated with alglucosidase-alfa enzyme replacement therapy (ERT); however, he was eventually diagnosed to carrying a PRKAG2 pathogenic gene mutation; he did not have Pompe disease instead he was a carrier for the common adult leaky splice site mutation in the GAA gene.
At 2.5months, the patient had hypotonia/generalized muscle weakness, a diagnosis of non-classic infantile Pompe disease was made based on low acid alpha-glucosidase activity and the patient started on ERT at 11months. However, 1month later, the patient began to have seizures. As the patient's medical history was somewhat unusual for infantile Pompe disease, further evaluation was initiated and included a glycogen storage disease sequencing panel which showed that the patient had a pathogenic mutation in PRKAG2 which had been reported previously. ERT was discontinued and patient had a progression of motor deficits. ERT was reinitiated by the treating physician, and a clinical benefit was noted.
This report outlines the benefits of ERT with alglucosidase alfa in a patient with PRKAG2 syndrome, the decline in his condition when the ERT infusions were discontinued, and the significant positive response when ERT was reinitiated.
PRKAG2综合征是一种常染色体显性疾病，其特征为严重的婴儿肥厚型心肌病和心律紊乱，部分病例起病较晚，临床表现多样，包括心脏表现、肌病和癫痫发作。PRKAG2综合征的心脏特征与庞贝病的心脏表现相似。我们报告一名最初被诊断为庞贝病并接受阿糖苷酶α酶替代疗法（ERT）治疗的患者；然而，他最终被诊断携带PRKAG2致病基因突变；他并非患有庞贝病，而是GAA基因常见成人渗漏剪接位点突变的携带者。
患者2.5个月时出现肌张力减退/全身肌无力，基于低酸性α-葡萄糖苷酶活性诊断为非典型婴儿庞贝病，患者于11个月时开始接受ERT治疗。然而，1个月后，患者开始出现癫痫发作。由于该患者的病史对于婴儿庞贝病来说有些不寻常，因此展开了进一步评估，包括糖原贮积病测序分析，结果显示患者存在先前已报道的PRKAG2致病突变。ERT治疗中断，患者运动功能障碍进展。治疗医生重新开始ERT治疗，并观察到临床获益。
本报告概述了阿糖苷酶αERT治疗PRKAG2综合征患者的益处、ERT输注中断时患者病情的恶化情况以及重新开始ERT治疗时显著的阳性反应。
