Guay-Woodford Lisa M
Center for Translational Science, Children's National Health System, Washington, USA.
J Pediatr Genet. 2014;3(2):89-101. doi: 10.3233/PGE-14092.
Autosomal recessive polycystic kidney disease (ARPKD) is a severe, typically early onset form of renal cystic disease. The care of ARPKD patients has traditionally been the purview of pediatric nephrologists for management of systemic hypertension and progressive renal insufficiency. However, the disease has multisystem manifestations and a comprehensive care strategy frequently requires a multidisciplinary team. In severely affected infants, the diagnosis often is first suspected by obstetricians when enlarged, echogenic kidneys and oligohydramnios are detected on prenatal ultrasounds. Neonatologists are central to the care of these infants, who may have respiratory compromise due to pulmonary hypoplasia and massively enlarged kidneys. Among neonatal survivors, a subset of ARPKD patients has clinically significant congenital hepatic fibrosis, which can lead to portal hypertension, requiring close monitoring by pediatric hepatologists. Surgical consultation may be sought to access pre-emptive nephrectomy to relieve mass effect, placement of dialysis access, surgical shunting procedures, and kidney and/or liver transplantation. Recent data suggest that children with ARPKD may be at risk of neurocognitive dysfunction, and may require neuropsychological referral. In addition to these morbidities, families of patients with ARPKD face decisions regarding genetic testing of affected children, testing of asymptomatic siblings, or consideration of preimplantation genetic diagnosis for future pregnancies. These issues require the input of genetic counselors, geneticists, and reproductive endocrinologists. As a result, the management of ARPKD requires the involvement of multiple subspecialists, as well as the general pediatrician, in a complex care network. In this review, we discuss the genetics of this disorder and provide an overview of the associated pathobiology; outline the spectrum of clinical manifestations of ARPKD and the management of organ-specific complications; discuss other disorders that involve genes encoding cilia-associated proteins that can clinically mimic ARPKD; review the animal models available for preclinical studies; and finally, consider future directions for potential targeted therapies.
常染色体隐性多囊肾病（ARPKD）是一种严重的、通常发病较早的肾囊性疾病。传统上，ARPKD患者的护理由儿科肾病学家负责，以管理系统性高血压和进行性肾功能不全。然而，该疾病具有多系统表现，全面的护理策略通常需要多学科团队。在严重受影响的婴儿中，产科医生在产前超声检查中发现肾脏增大、回声增强和羊水过少时，通常首先怀疑该病。新生儿科医生对于这些婴儿的护理至关重要，这些婴儿可能因肺发育不全和肾脏巨大而出现呼吸功能不全。在新生儿幸存者中，一部分ARPKD患者有临床上显著的先天性肝纤维化，这可能导致门静脉高压，需要儿科肝病学家密切监测。可能需要寻求外科会诊，以进行预防性肾切除术以减轻肿块效应、建立透析通路、进行手术分流程序以及进行肾脏和/或肝脏移植。最近的数据表明，ARPKD患儿可能有神经认知功能障碍的风险，可能需要进行神经心理学转诊。除了这些疾病外，ARPKD患者的家庭还面临着关于对患病儿童进行基因检测、对无症状的兄弟姐妹进行检测或考虑对未来妊娠进行植入前基因诊断的决策。这些问题需要遗传咨询师、遗传学家和生殖内分泌学家的参与。因此，ARPKD的管理需要多个亚专科医生以及普通儿科医生参与到一个复杂的护理网络中。在这篇综述中，我们讨论了这种疾病的遗传学，并概述了相关的病理生物学；概述了ARPKD的临床表现谱和器官特异性并发症的管理；讨论了其他涉及编码与纤毛相关蛋白的基因的疾病，这些疾病在临床上可能与ARPKD相似；回顾了可用于临床前研究的动物模型；最后，考虑了潜在靶向治疗的未来方向。
