Late-Onset Ornithine Transcarbamylase Deficiency Complicated with Extremely High Serum Ammonia Level: Prompt Induction of Hemodialysis as the Key to Successful Treatment

Abstract

Patient: Male, 35-year-old Final Diagnosis: Late-onset ornithine transcarbamylase deficiency Symptoms: Disturbance of consciousness • headache • vomiting Medication: — Clinical Procedure: Genetic analysis Specialty: Genetics • Metabolic Disorders and Diabetics Objective: Rare disease Background: Ornithine transcarbamylase deficiency (OTCD) is an X-linked semi-dominant disorder, causing possible fatal hyperammonemia. Late-onset OTCD can develop at any time from 2 months after birth to adulthood, accounting for 70% of all OTCDs. Case Report: A 35-year-old man with chronic headaches stated that since childhood he felt sick after eating meat. Fourteen days before hospital admission, he began receiving 60 mg/day of intravenous prednisolone for sudden deafness. The prednisolone was stopped 5 days before hospital admission. Four days later, he was transferred to our hospital because of confusion. On admission, he had hyperammonemia of 393 µmol/L. Because he became comatose 7 hours after admission, and his serum ammonia increased to 1071 µmol/L, we promptly started hemodialysis. Because his family history included 2 deceased infant boys, we suspected late-onset OTCD. On day 2 of hospitalization, we began administering ammonia-scavenging medications. Because he gradually regained consciousness, we stopped his hemodialysis on day 6. After his general condition improved, he was transferred to the previous hospital for rehabilitation on day 32. We definitively diagnosed him with late-onset OTCD due to the low plasma citrulline and high urinary orotic acid levels found during his hospitalization. Conclusions: Clinicians should suspect urea cycle disorders, such as OTCD, when adult patients present with marked hyper-ammonemia without liver cirrhosis. Adult patients with marked hyperammonemia should immediately undergo hemodialysis to remove ammonia, regardless of causative diseases.

Diagnostic and Management Issues in Patients with Late-Onset Ornithine Transcarbamylase Deficiency

“…Mortality is a key indicator for the further evaluation of the diagnosis of the late-onset phenotype [21,28]. A meta-analysis by Burgard et al (2016) has shown that all UCDs, apart from females with OTCD, have a high risk of early-onset manifestations and neonatal death [20].…”

“…Patients may present with chronic migraine headaches or neurological signs of hyperammonemia such as lethargy, disorientation, agitation, confusion, reduced consciousness and prolonged generalized seizures. An initial presentation with psychiatric symptoms can occur and OTCD should be considered in adolescents with new-onset psychosis or bipolar-like symptoms [ 21 , 26 , 27 , 29 , 30 , 31 , 32 ].…”

“…Clinical symptoms can be aggravated by metabolic stressors (an increased protein consumption including the use of sport supplements, infection, trauma, fever, severe illness and acute stress) or presence of a catabolic state (intrapartum and immediate postpartum, menstruation, gastric bypass surgery, starvation and fasting), or due to increased demands upon the urea cycle (systemic corticosteroids, rapid weight loss, gastrointestinal bleeding trauma and chemotherapy) [ 19 , 21 , 26 , 27 , 31 , 33 , 34 , 35 , 36 ]. Apart from steroids (dexamethasone, hydrocortisone and methylprednisolone) and chemotherapy, anticonvulsants (valproate and topiramate), metoclopramide and azathioprine may increase demands on the urea cycle, thus triggering an initial OTCD presentation [ 37 ].…”

“…In addition, underlying morbidities such as cardiac dysfunction and nonalcoholic fatty liver disease also unmask the OTCD in adults [ 24 ]. As hyperammonemia may become apparent in these patients during acute metabolic decompensation [ 21 ], it is important to consider and initiate the relevant investigations.…”

“…Those with late-onset OTCD can develop symptoms anytime from infancy to later childhood, adolescence or adulthood [ 21 ]. Hemizygous males with a partial enzyme deficiency and around 20% of heterozygous females fall into this category.…”