背景:Nephronophisis(NPHP)是一种常染色体隐性遗传疾病,有一部分患者表现为肾外表现,如视网膜变性,小脑共济失调,肝纤维化,骨骼异常,心脏畸形,和肺支气管扩张.然而,其他器官系统的参与也有记录。肾外表现发生在大约10-20%的患者中。在发达国家,据报道,在生命的前三十年中,它是单基因慢性肾衰竭(CKF)的最常见原因之一,有超过25个基因与这种情况有关。目前管理NPHP的治疗方案包括支持治疗,并发症的管理,必要时进行肾脏替代疗法。索引患者是一名10岁的白人女性,她反复发作腹痛。她的姐姐,TN,17岁,被诊断为CKF,并注意到肝酶持续升高(γ-谷氨酰转移酶,丙氨酸,和天冬氨酸转氨酶)。基因检测后,她的姐姐被证明患有3型Nephronophisis,肝活检显示早期纤维化变化。随后的基因检测证实该指标患者患有NPHP3型。肾脏活检显示局灶性硬化的肾小球,伴有肾小管萎缩的斑片状区域和相关的肾小管间质变化,与NPHP保持一致。我们介绍了第一例来自南非的NPHP的确诊病例,该病例基于组织病理学和基因检测,在一名10岁的白人女性中表现出反复发作的腹痛,他的姐姐也出现了CKF和早期肝纤维化,活检和基因检测证实。
结论:在中低收入国家,应尽可能进行基因检测以确认NPHP的诊断,尤其是那些提示活检或病因不明的CKF伴或不伴肾外表现的患者。
BACKGROUND: Nephronophthisis (NPHP) is an autosomal recessive disorder with a subset of patients presenting with extrarenal manifestations such as retinal degeneration, cerebella ataxia, liver fibrosis, skeletal abnormalities, cardiac malformations, and lung bronchiectasis. However, the involvement of other organ systems has also been documented. Extrarenal manifestations occur in approximately 10-20% of patients. In developed countries, it has been reported as one of the most common causes of monogenic chronic kidney failure (CKF) during the first three decades of life, with more than 25 genes associated with this condition. The current treatment options for managing NPHP include supportive care, management of complications, and kidney replacement therapy when necessary. The index patient is a 10-year-old Caucasian female who presented with recurrent attacks of abdominal pain. Her elder sister, TN, who was 17 years old, was diagnosed with CKF and noted to have persistently elevated liver enzymes (gamma-glutamyl transferase, alanine, and aspartate transaminases). Following genetic testing, her elder sister was shown to have Nephronophthisis Type 3, and a liver biopsy showed early fibrotic changes. Subsequent genetic testing confirmed the index patient as having NPHP Type 3. A kidney biopsy showed focal sclerosed glomeruli with patchy areas of tubular atrophy and related tubulointerstitial changes in keeping with NPHP. We present the first confirmatory case of NPHP from South Africa based on histopathology and genetic testing in a 10-year-old Caucasian female who presented with recurrent attacks of abdominal pain, whose elder sister also presented with CKF and early liver fibrosis, confirmed on biopsy and genetic testing.
CONCLUSIONS: In low-middle-income countries, genetic testing should be undertaken whenever possible to confirm the diagnosis of NPHP, especially in those with a suggestive biopsy or if there is CKF of unknown aetiology with or without extra-renal manifestations.