Hackl Agnes, Mehler Katrin, Gottschalk Ingo, Vierzig Anne, Eydam Marcus, Hauke Jan, Beck Bodo B, Liebau Max C, Ensenauer Regina, Weber Lutz T, Habbig Sandra
Pediatric Nephrology, Children's and Adolescents' Hospital, University Hospital of Cologne, Kerpener Street 62, 50937, Cologne, Germany.
Department of Neonatology and Pediatric Intensive Therapy, Children's and Adolescents' Hospital, University Hospital of Cologne, Cologne, Germany.
Pediatr Nephrol. 2017 May;32(5):791-800. doi: 10.1007/s00467-016-3556-5. Epub 2017 Jan 12.
Differential diagnosis of prenatally detected hyperechogenic and enlarged kidneys can be challenging as there is a broad phenotypic overlap between several rare genetic and non-genetic disorders. Metabolic diseases are among the rarest underlying disorders, but they demand particular attention as their prognosis and postnatal management differ from those of other diseases.
We report two cases of cystic, hyperechogenic and enlarged kidneys detected on prenatal ultrasound images, resulting in the suspected diagnosis of autosomal recessive polycystic kidney disease (ARPKD). Postnatal clinical course and work-up, however, revealed early, neonatal forms of disorders of fatty acid oxidation (DFAO) in both cases, namely, glutaric acidemia type II, based on identification of the novel, homozygous splice-site mutation c.1117-2A > G in the ETFDH gene, in one case and carnitine palmitoyltransferase II deficiency in the other case.
Review of pre- and postnatal sonographic findings resulted in the identification of some important differences that might help to differentiate DFAO from ARPKD. In DFAO, kidneys are enlarged to a milder degree than in ARPKD, and the cysts are located ubiquitously, including also in the cortex and the subcapsular area. Interestingly, recent studies have pointed to a switch in metabolic homeostasis, referred to as the Warburg effect (aerobic glycolysis), as one of the underlying mechanisms of cell proliferation and cyst formation in cystic kidney disease. DFAO are characterized by the inhibition of oxidative phosphorylation, resulting in aerobic glycolysis, and thus they do resemble the Warburg effect. We therefore speculate that this inhibition might be one of the pathomechanisms of renal hyperproliferation and cyst formation in DFAO analogous to the reported findings in ARPKD.
Neonatal forms of DFAO can be differentially diagnosed in neonates with cystic or hyperechogenic kidneys and necessitate immediate biochemical work-up to provide early metabolic management.
产前检测到的高回声且增大的肾脏的鉴别诊断具有挑战性，因为几种罕见的遗传和非遗传疾病之间存在广泛的表型重叠。代谢性疾病是最罕见的潜在疾病之一，但由于其预后和产后管理与其他疾病不同，因此需要特别关注。
我们报告了两例产前超声图像上检测到的囊性、高回声且增大的肾脏病例，初步怀疑为常染色体隐性多囊肾病（ARPKD）。然而，产后临床病程及检查结果显示，两例均为脂肪酸氧化障碍（DFAO）的早期新生儿型疾病，一例为II型戊二酸血症，基于在ETFDH基因中发现新的纯合剪接位点突变c.1117-2A＞G，另一例为肉碱棕榈酰转移酶II缺乏症。
回顾产前和产后超声检查结果，发现了一些有助于区分DFAO和ARPKD的重要差异。在DFAO中，肾脏增大程度比ARPKD轻，囊肿分布广泛，包括皮质和包膜下区域。有趣的是，最近的研究指出，代谢稳态的转变，即所谓的瓦伯格效应（有氧糖酵解），是囊性肾病中细胞增殖和囊肿形成的潜在机制之一。DFAO的特征是氧化磷酸化受到抑制，导致有氧糖酵解，因此它们确实类似于瓦伯格效应。因此，我们推测这种抑制可能是DFAO中肾脏过度增殖和囊肿形成的发病机制之一，类似于ARPKD中报道的发现。
新生儿型DFAO可在患有囊性或高回声肾脏的新生儿中进行鉴别诊断，并且需要立即进行生化检查以提供早期代谢管理。
