Disorders of fatty acid oxidation and autosomal recessive polycystic kidney disease-different clinical entities and comparable perinatal renal abnormalities

Pediatr Nephrol. 2017 May;32(5):791-800. doi: 10.1007/s00467-016-3556-5. Epub 2017 Jan 12.


Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: ARPKD; DFAO; Hyperammonemia; Neonatal kidney failure; Renal oligohydramnios; Ultrasound; Warburg effect.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Electron-Transferring Flavoproteins / genetics
  • Fatal Outcome
  • Fatty Acids / metabolism*
  • Female
  • Glutarates / blood
  • Humans
  • Infant, Newborn
  • Iron-Sulfur Proteins / genetics
  • Kidney / diagnostic imaging*
  • Lipid Metabolism, Inborn Errors / diagnostic imaging*
  • Lipid Metabolism, Inborn Errors / metabolism
  • Lipid Metabolism, Inborn Errors / therapy
  • Mutation
  • Oxidoreductases Acting on CH-NH Group Donors / genetics
  • Polycystic Kidney, Autosomal Recessive / diagnostic imaging*
  • Polycystic Kidney, Autosomal Recessive / metabolism
  • Polycystic Kidney, Autosomal Recessive / therapy
  • Pregnancy
  • Ultrasonography
  • Ultrasonography, Prenatal
  • Young Adult


  • Electron-Transferring Flavoproteins
  • Fatty Acids
  • Glutarates
  • Iron-Sulfur Proteins
  • Oxidoreductases Acting on CH-NH Group Donors
  • electron-transferring-flavoprotein dehydrogenase
  • glutaric acid