Gumm Alexis J, Basel Donald G, Thakrar Pooja, Suchi Mariko, Telega Grzegorz
Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
Division of Pediatric Genetics, Department of Genetics, Medical College of Wisconsin, Milwaukee, WI, USA.
Pediatr Transplant. 2020 Dec;24(8):e13808. doi: 10.1111/petr.13808. Epub 2020 Aug 13.
Patients with defects in the ATP6AP1 gene have rarely been described. ATP6AP1-related disorders are a subtype of CDG, which result in enzyme deficiencies affecting multiple organ systems ranging from mild to life-threatening. Of the 13 patients described, all had hepatopathy, but this is the first case to be successfully transplanted. We describe two brothers who developed hyperbilirubinemia shortly after birth and progressed to liver failure, case 1 by 12 months of age, with successful transplant 2 years later, and case 2 by 4 months of age, who passed away while awaiting liver transplant. Both boys were found to have a new variant in the ATP6AP1 gene: c.932/p.Leu311Gln. Although the identified ATP6AP1 gene variant was classified as unknown significance at the time, both children's phenotypes fit with what has been described for ATP6AP1-related disorders. Therefore, this result appears to have been diagnostic for both boys. This rare type of CDG, X-linked immunodeficiency type 47 (OMIM #300972), particularly in patients who progress to liver failure requiring transplant, should be included on the differential of liver failure in infants and toddlers, and its gene should be added to the diagnostic workup for such cases.
ATP6AP1基因缺陷的患者鲜有报道。ATP6AP1相关疾病是先天性糖基化障碍（CDG）的一种亚型，可导致影响多个器官系统的酶缺乏，症状从轻到危及生命不等。在已报道的13例患者中，均有肝病，但这是首例成功接受移植的病例。我们描述了两名兄弟，他们出生后不久即出现高胆红素血症，并进展为肝衰竭，病例1在12个月大时出现肝衰竭，2年后成功接受移植；病例2在4个月大时出现肝衰竭，在等待肝移植期间死亡。两名男孩均被发现ATP6AP1基因存在新的变异：c.932/p.Leu311Gln。尽管当时鉴定出的ATP6AP1基因变异被归类为意义不明，但两个孩子的表型均符合ATP6AP1相关疾病的描述。因此，这一结果似乎对两个男孩都具有诊断意义。这种罕见的CDG类型，即X连锁免疫缺陷47型（OMIM #300972），尤其是对于进展为需要移植的肝衰竭患者，应列入婴幼儿肝衰竭的鉴别诊断范围，并且其基因应添加到此类病例的诊断检查中。
