title: Disorders of fatty acid oxidation and autosomal recessive polycystic kidney disease-different clinical entities and comparable perinatal renal abnormalities.
abstract: 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.
authors.affiliation: Pediatric Nephrology, Children's and Adolescents' Hospital, University Hospital of Cologne, Kerpener Street 62, 50937, Cologne, Germany. agnes.hackl@uk-koeln.de.
authors.forename: Agnes
authors.initials: A
authors.lastname: Hackl
authors.affiliation: Department of Neonatology and Pediatric Intensive Therapy, Children's and Adolescents' Hospital, University Hospital of Cologne, Cologne, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Mehler
authors.affiliation: Division of Prenatal Medicine, Department of Obstetrics and Gynecology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Gottschalk
authors.affiliation: Department of Neonatology and Pediatric Intensive Therapy, Children's and Adolescents' Hospital, University Hospital of Cologne, Cologne, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Vierzig
authors.affiliation: Department of Pediatric Radiology, Institute for Radiology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Eydam
authors.affiliation: Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Hauke
authors.affiliation: Institute for Human Genetics, University Hospital of Cologne, Cologne, Germany.
authors.forename: Bodo B
authors.initials: BB
authors.lastname: Beck
authors.affiliation: Pediatric Nephrology, Children's and Adolescents' Hospital, University Hospital of Cologne, Kerpener Street 62, 50937, Cologne, Germany.|Nephrology Research Laboratory, Department II of Internal Medicine, University Hospital of Cologne, Cologne, Germany.|Center for Molecular Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Max C
authors.initials: MC
authors.lastname: Liebau
authors.affiliation: Experimental Pediatrics and Metabolism, Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Ensenauer
authors.affiliation: Pediatric Nephrology, Children's and Adolescents' Hospital, University Hospital of Cologne, Kerpener Street 62, 50937, Cologne, Germany.
authors.forename: Lutz T
authors.initials: LT
authors.lastname: Weber
authors.affiliation: Pediatric Nephrology, Children's and Adolescents' Hospital, University Hospital of Cologne, Kerpener Street 62, 50937, Cologne, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Habbig
mesh_terms: D000328:Adult; D044927:Electron-Transferring Flavoproteins / Q000235:genetics; D017809:Fatal Outcome; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005977:Glutarates / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D007506:Iron-Sulfur Proteins / Q000235:genetics; D007668:Kidney / Q000000981:diagnostic imaging*; D008052:Lipid Metabolism, Inborn Errors / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000628:therapy; D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D017044:Polycystic Kidney, Autosomal Recessive / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000628:therapy; D011247:Pregnancy; D014463:Ultrasonography; D016216:Ultrasonography, Prenatal; D055815:Young Adult
chemical_list: D044927:Electron-Transferring Flavoproteins; D005227:Fatty Acids; D005977:Glutarates; D007506:Iron-Sulfur Proteins; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase; C035736:glutaric acid
keywords: ARPKD; DFAO; Hyperammonemia; Neonatal kidney failure; Renal oligohydramnios; Ultrasound; Warburg effect