High blood pressure, a red flag for the neonatal manifestation of urea cycle disorders

Orphanet J Rare Dis. 2019 Apr 8;14(1):80. doi: 10.1186/s13023-019-1055-z.


Background: Neonatal manifestation of life-threatening hyperammonemic encephalopathy in urea cycle disorders (UCD) is often misdiagnosed as neonatal sepsis, resulting in significantly delayed start of specific treatment and poor outcome. The major aim of this study was to identify specific initial symptoms or signs to clinically distinguish hyperammonemic encephalopathy in neonates from neonatal sepsis in order to identify affected individuals with UCD and to start metabolic therapy without delay. Furthermore, we evaluated the impact of diagnostic delay, peak plasma ammonium (NH4+) concentration, mode of emergency treatment and transfer to a tertiary referral center on the outcome.

Methods: Detailed information of 17 patients (born between 1994 and 2012) with confirmed diagnosis of UCD and neonatal hyperammonemic encephalopathy were collected from the original medical records.

Results: The initially suspected diagnosis was neonatal sepsis in all patients, but was not confirmed in any of them. Unlike neonatal sepsis and not previously reported blood pressure increased above the 95th percentile in 13 (81%) of UCD patients before emergency treatment was started. Respiratory alkalosis was found in 11 (65%) of UCD patients, and in 14 (81%) plasma NH4+concentrations further increased despite initiation of metabolic therapy.

Conclusion: Detection of high blood pressure could be a valuable parameter for distinguishing neonatal sepsis from neonatal manifestation of UCD. Since high blood pressure is not typical for neonatal sepsis, other reasons such as encephalopathy and especially hyperammonemic encephalopathy (caused by e.g. UCD) should be searched for immediately. However, our result that the majority of newborns with UCD initially present with high blood pressure has to be evaluated in larger patient cohorts.

Keywords: Clinical presentation; Hyperammonemic encephalopathy; Hypertension; Neonatal urea cycle disorders.

MeSH terms

  • Alkalosis, Respiratory / diagnosis
  • Brain Diseases / diagnosis*
  • Delayed Diagnosis
  • Female
  • Humans
  • Hyperammonemia / diagnosis*
  • Hypertension / diagnosis*
  • Infant, Newborn
  • Male
  • Sepsis / diagnosis
  • Urea Cycle Disorders, Inborn / diagnosis*