Profound metabolic acidosis and oxoprolinuria in an adult

Abstract

Profound metabolic acidosis is a medical emergency that requires prompt recognition to ensure acute, appropriate management. Early, potentially life saving therapies may include hemodialysis for a toxic alcohol ingestion, insulin for diabetic ketoacidosis, antibiotics for sepsis, and in some cases drug withdrawal-such as for metformin or nucleoside analogue reverse transcriptase inhibitor associated lactic acidosis. The etiology of metabolic acidosis rarely remains elusive. We are reporting a case of profound metabolic acidosis due to accumulation of the organic acid 5-oxoproline. Case ReportA 58-year-old female presented in a confused state to the emergency department of a small community hospital. The patient's husband reported that his wife had been confused for several days. He also reported she had not been eating well, had diminished hearing, and (most recently) rapid breathing; this prompted him to bring the patient to the emergency department.Her past medical history included analgesic and diazepam abuse, alcoholism, anxiety, depression, an eating disorder, COPD, and migraines. Current medications included fluoxetine, diazepam, lansoprazole, conjugated estrogen, and sumatriptan.A physical examination revealed a disheveled, cachectic female. She was tachypneic and had difficulty hearing. Blood pressure was 171/93 mm Hg, heart rate was 80 beats per minute, respiratory rate was 35 breaths per minute, and rectal temperature was 32.5°C. Her pupils were normal and sclera were without icterus. No fruity or other odor was appreciated on her breath. Chest, heart, and abdominal exams were unremarkable. Her extremities were cool and mottled. A neurological exam at presentation did not indicate any focal-motor deficits. Profound Metabolic Acidosis and Oxoprolinuria in an Adult ABSTRACTIntroduction: Profound metabolic acidosis in critically ill adults sometimes remains unexplained despite extensive evaluation. Case Report: A 58-year-old female presented in a confused state to the emergency department; she had been confused for several days. Laboratory evaluation revealed a high anion gap metabolic acidosis and modestly elevated acetaminophen level. Lactic acid was only modestly elevated. There was no evidence of ketoacids, salicylate, methanol, or ethylene glycol. A urine sample submitted on day 1 of hospitalization revealed a markedly elevated level of 5-oxoproline.Discussion: Originally described in children with an inherited defect of glutathione synthetase, 5-Oxoproline is an unusual cause of metabolic acidosis. More recently this disturbance has been recognized in critically ill adults without a recognized inherited metabolic disorder. In most of these cases there has been the concomitant use of acetaminophen. Any causal relationship between acetaminophen and this disturbance is speculative. Conclusion:In critically ill adults with unexplained metabolic acidosis, 5-Oxoproline should be considered in the differential.

Profound metabolic acidosis from pyroglutamic acidemia: an underappreciated cause of high anion gap metabolic acidosis

“…14 The typical presentation occurs in a patient who develops an acutely altered level of consciousness and the clinical manifestations of metabolic acidosis during a prolonged hospital stay. There are, however, cases of patients presenting from home, [5][6][7]14,15,17,18 and our case supports evidence that patients can present without significant comorbidity other than malnutrition. It is important to note that our patient's pyroglutamic metabolic acidosis was in the context of chronic acetaminophen use in the face of malnutrition and was not associated with the metabolic acidosis seen in acetaminophen overdose that is usually accompanied by hepatic and renal failure.…”

5-Oxoprolinemia Causing Elevated Anion Gap Metabolic Acidosis in the Setting of Acetaminophen Use

“…There have been at least 28 other cases of APAPassociated 5-oxoprolinemia reported in the literature (9)(10)(11)(12)(13)(14)(15)(16). Risk factors common to these patients include malnutrition, female gender, underlying infection, renal insufficiency and, importantly, chronic APAP ingestion over protracted periods of time.…”

Understanding lactic acidosis in paracetamol (acetaminophen) poisoning

“…An alternative explanation that has been suggested for such cases is the occurrence of transient acquired pyroglutamic acidaemia (or 5-oxoprolinuria) [50]. Pyroglutamic acidaemia can cause depressed conscious level and metabolic acidosis with a relatively normal lactate [51]. It typically occurs in unwell hospital patients given therapeutic doses of paracetamol over a number of days [52][53][54][55][56][57][58].…”