Peak hyperammonemia and atypical acute liver failure: The eruption of an urea cycle disorder during hyperemesis gravidarum

Abstract

Inborn urea cycle disorders are under-recognised metabolic causes of hyperammonemia in adults. A 28-year-old primigravida, seven weeks pregnant, affected by hyperemesis gravidarum developed acute liver injury (ALI) and then acute liver failure (ALF) in less than 48 h. Because the patient developed atypical features, especially mildly elevated aminotransferases contrasting with very high blood ammonia levels (281 μmol/L), concomitant with normal serum creatinine, an inborn error of metabolism was suspected. We performed emergency metabolic analyses, stopped all protein intake and started with intravenous (i.v.) high caloric intake, nitrogen scavenger drugs and haemodialysis. The neurological and hepatic status of the patient quickly improved together with normalisation of her ammonemia levels. High plasma glutamine and urinary orotic acid, alongside low plasma arginine, citrulline and ornithine were suggestive of an ornithine transcarbamylase deficiency, later confirmed by molecular analyses. Foetal sex was female, as determined by foetal DNA analysis in maternal blood, and foetal development was unremarkable throughout the pregnancy. Delivery was induced at 39 weeks with a close monitoring of ammonemia levels and i.v. perfusion of carbohydrates and lipids during labour and immediately post-partum to avoid hypercatabolism. Delivery was uneventful and the patient delivered a healthy female baby. Urea cycle disorders should be contemplated in non-jaundiced patients with ALI or ALF, severe hyperammonemia and normal serum creatinine regardless of serum aminotransferase levels. The prompt recognition of this rare condition and the rapid initiation of adequate metabolic therapy are mandatory to prevent irreversible neurological sequelae and to avoid liver transplantation.

Neurological Complications Occurring After Liver Transplantation: Role of Risk Factors, Hepatic Encephalopathy, and Acute (on Chronic) Brain Injury

“…Indeed, even if confounding factors exist, especially the association with systemic inflammation, persistent postoperative cognitive impairment may still be correlated with bouts of HE and their severity . Long‐lasting decompensation due to urea cycle defects, the most frequent inborn error of metabolism responsible for hyperammonemia, is clearly linked to neurological impairment, validating the need for ammonia‐lowering strategies. In ALF, the rapid onset of hyperammonemia could explain the neurological sequelae that follows HE.…”

Challenges in diagnosing and managing adult patients with urea cycle disorders

“…The diagnosis of OCTD may become apparent during periods of metabolic stress such as during pregnancy or the postpartum period . Pregnancy favors both prolonged fasting due to hyperemesis gravidarum and/or increased energy demands during the puerperium and therefore can reveal UCD …”

“…5 Pregnancy favors both prolonged fasting due to hyperemesis gravidarum and/or increased energy demands during the puerperium and therefore can reveal UCD. 24 Hyperemesis gravidarum, a risk factor for metabolic decompensation due to caloric deficit, may be both a cause, and consequence, of hyperammonemia. Complications of hyperammonemia in pregnancy can masquerade as more common problems.…”

Review of Multi-Modal Imaging in Urea Cycle Disorders: The Old, the New, the Borrowed, and the Blue

“…Because many adult physicians are not familiar with the UCD, and because the clinical presentation may mimic other conditions that also present with acute confusional states or psychosis, they may be difficult to diagnose, if at all. The triggers of adult disease may be brought on by various metabolic stressors such as chronic starvation, gastric bypass surgery, rapid weight loss, and changes in diet with protein loading (3), or the postpartum period in addition to illness and certain medications (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Since OTCD is X linked, female OTCD heterozygotes may show great variability in symptoms ranging from asymptomatic to significant clinical symptoms.…”