Pyruvate dehydrogenase complex deficiency masked by septic shock-induced lactic acidosis: a case report.

Pyruvate dehydrogenase complex (PDHC) deficiency is a common genetic disorder leading to lactic acidosis, which can also result from several nongenetic conditions, such as septic shock. The present study reports a case of PDHC deficiency masked by septic shock-induced lactic acidosis. This case involved a 16-year-old adolescent with poor exercise tolerance compared with his peers, and no underlying diseases. The disease onset was characterized by cough, fever, and dyspnea, with hypotension and elevated lactate levels, which indicated septic shock. However, severe hypoglycemia and lactic acidosis persisted despite resolution of a pulmonary infection and correction of septic shock, requiring continuous intravenous infusion of 50% glucose. Although the patient did not experience acute kidney injury and had normal urine output, continuous renal replacement therapy was used to regulate the internal environment owing to the severity of the acidosis. The diagnosis of PDHC deficiency was considered on the basis of the persistent hypoglycemia and hyperlactatemia, before genetic mutation testing was completed. The clinical thinking process required a rich accumulation of pathophysiological knowledge. This article reports a case of PDHC deficiency masked by septic shock-induced lactic acidosis to raise awareness of the disease and avoid misdiagnosis and missed diagnosis.

Linezolid-induced lactic acidosis.

Linezolid is a commonly prescribed antibiotic in clinical practice. Although thrombocytopenia and peripheral neuropathy are frequently encountered following prolonged administration of linezolid, lactic acidosis is a rare adverse drug reaction. We present the case of a patient on linezolid for disseminated multidrug-resistant tuberculosis who presented with vomiting, dyspnoea, hypotension and high anion gap metabolic acidosis. The initial presentation mimicked sepsis syndrome. Ketoacidosis and renal dysfunction were ruled out. There was no history of ingestion of toxins/toxic alcohols. Sepsis was unlikely because extensive radiological and microbiological testing could not identify an infection. Given the possibility of linezolid-induced lactic acidosis (LILA), linezolid was discontinued on admission. The patient's lactic acidosis resolved, and his overall condition improved. A retrospective diagnosis of LILA was thus established. LILA should be considered when patients on linezolid present with lactic acidosis and other causes for the lactic acidosis have been ruled out.

Adult-onset mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS): a diagnostic challenge.

Rare causes of stroke-like presentations can be difficult to diagnose. We report a case of a man in his 40s who first presented with stroke symptoms, but whose clinical course was not typical for a stroke. A detailed investigation of the patient's medical history revealed bilateral sensorineural hearing loss which prompted a wider diagnostic assessment.Furthermore, lack of vascular risk factors and a normal angiogram strengthened our suspicion of an unusual underlying condition. Raised lactic acid levels and genetic analysis confirmed a diagnosis of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome.

Malignancy Associated Type B Lactic Acidosis: A Rare, yet Fascinating Oncological Emergency.

Type B lactic acidosis has been described infrequently in hematologic malignancies, but even less often in solid tumors. Since 1978, there have been only 58 cases of solid tumor associated Type B lactic acidosis described in the literature. Lung cancer (neuroendocrine) is the most common tumor; others frequently have a poorly/undifferentiated histology. The prognosis is dismal. Malignancy associated type B lactic acidosis is not associated with hypoxemia. The most highlighted pathogenetic mechanism is the Warburg effect (aerobic glycolysis of tumor cells causing excess lactate). We describe a patient with metastatic GI neuroendocrine carcinoma with profound lactic acidosis, who died within 24 hours. When extremely ill cancer patients present with lactic acidosis, sepsis is usually a primary concern. This case highlights the need for providers to consider malignancy associated lactic acidosis (MA-LA) in the differential diagnosis, particularly in patients with advanced malignancies, of lung origin, of neuroendocrine or poorly/undifferentiated histologic subtypes. The implications and approach are distinct from Type A/D lactic acidosis, and would involve treatment of the underlying malignancy at the earliest.

An Elusive Diagnosis: Diffuse Large B-Cell Lymphoma Masquerading as Acute Liver Failure with Persistent Lactic Acidosis.

BACKGROUND Acute liver failure (ALF) associated with malignant lymphoma is a rare condition with non-specific clinical and radiological features. Here, we describe an unusual case of ALF due to DLBCL with an image negative on presentation posing diagnostic difficulty. CASE REPORT A 74-year-old man was admitted to our hospital with abdominal pain. Radiological and laboratory investigations revealed lymphadenopathy with mildly elevated transaminitis and alkaline phosphates levels. A right upper-quadrant ultrasound showed heterogeneous hepatic parenchyma. Eight days later, he had worsening abdominal pain. He was found to have altered mental status and asterixis. His liver function was worsened with ALT 101, AST 328, lactic acid 4.2, total bilirubin 2.5, INR 6.35, and ammonia level 117 µmol/L. He continued to deteriorate with worsening lactic acidosis, coagulopathy, severe anemia, elevated liver enzymes, and thrombocytopenia. Unfortunately, the patient died of multi-organ failure on the 14th day of hospitalization. The autopsy findings revealed DLBCL involving multiple organs, including the liver, lung, bone marrow, and multiple lymph nodes. Despite an extensive diagnostic workup, an underlying diagnosis was unable to be established antemortem. CONCLUSIONS We describe a case of ALF linked to DLBCL discovered at autopsy. The non-specific clinical and radiological features of this condition make diagnosis challenging, and the prognosis is often poor. Further research and awareness are needed to improve the early detection and management of ALF associated with malignant lymphoma. By expanding the literature on this topic, we aim to improve outcomes and optimize patient care in similar clinical scenarios.

Α rare case of myopathy, lactic acidosis, and severe rhabdomyolysis, due to a homozygous mutation of the ferredoxin-2 (FDX2) gene.

Mitochondrial myopathy is a severe metabolic myopathy related to nuclear or mitochondrial DNA dysfunction. We present a rare case of mitochondrial myopathy, presented with multiple episodes of proximal muscle weakness, lactic acidosis, and severe rhabdomyolysis (CPK 319,990 U/L, lactic acid 22.31 mmol/L, and GFR 3.82 mL/min/1.73m2 ). She was hospitalized in the pediatric intensive care unit due to acute kidney injury, elevated blood pressure, and deterioration of respiratory and cardiac function. Investigation for inherited metabolic disorders showed elevated levels of ammonia, lactic acid to pyruvic acid ratio, and urine ketone bodies. Exome sequencing detected a homozygous pathogenic variant in FDX2 (ENST00000541276:p.Met4Leu/c.10A > T) and a heterozygous variant of uncertain significance in MSTO1 (ENST00000538143:p.Leu137Pro/c.410 T > C). After Sanger sequencing, the p.Met4Leu pathogenic variant in FDX2 (ENST00000541276:p.Met4Leu/c.10A > T) was identified in a heterozygous state in both her parents and sister. Recently, pathogenic variants in the FDX2 gene have been associated with mitochondrial myopathy, lactic acidosis, optic atrophy, and leukoencephalopathy. Only four reports of FDX2-related rhabdomyolysis have been described before, but none of the previous patients had hyperammonemia. This is a rare case of severe mitochondrial myopathy in a pediatric patient related to a pathogenic FDX2 variant, suggesting the need for genetic analysis of the FDX2 gene in cases of suspicion of mitochondrial myopathies.

Metformin-associated lactic acidosis reported to the United Kingdom National Poisons Information Service (NPIS) between 2010 and 2019: a ten-year retrospective analysis.

INTRODUCTION: Metformin toxicity following therapeutic use or overdose may result in metabolic acidosis with hyperlactatemia. This study aims to assess the relationship between serum lactate concentration, arterial pH, and ingested dose with severity of poisoning, and to identify if serum lactate concentration is a useful marker of severity in metformin toxicity. METHODS: A retrospective study of telephone enquiries relating to metformin exposures to the National Poisons Information Service between 2010 and 2019 from hospitals in the United Kingdom. RESULTS: Six-hundred and thirty-seven cases were identified; 117 involved metformin only and 520 involved metformin with other drugs. The majority of cases involved acute (87%) and intentional (69%) exposures. There was a statistically significant difference in doses between the Poisoning Severity Scores, as well as between intentional and unintentional or therapeutic error doses (P < 0.0001). The distribution of cases for each Poisoning Severity Score differed between the metformin only and metformin with other drugs cases (P < 0.0001). Lactic acidosis was reported in 232 cases. Serum lactate concentration and arterial pH differed across Poisoning Severity Scores. Arterial pH inversely correlated with ingested dose (r=-0.3, P = 0.003), and serum lactate concentration positively correlated with ingested dose (r = 0.37, P < 0.0001). Serum lactate concentration and arterial pH did not correlate with each other. Twenty-five deaths were recorded, all following intentional overdoses. DISCUSSION: The dataset focuses mostly on acute, intentional overdoses. Increasing ingested metformin dose, a higher serum lactate concentration and worsening arterial pH were all associated with an unfavourable Poisoning Severity Score in patients in both metformin only and metformin with other drugs groups. As serum lactate concentration did not correlate with arterial pH, it represents an independent marker of poisoning severity. CONCLUSIONS: Data from the present study suggest that serum lactate concentration can be used to assess severity of poisoning in patients who have reportedly ingested metformin.

Thiamine deficiency: a commonly unrecognised but easily treatable condition.

Thiamine is present in many foods and is well recognised as an essential nutrient critical for energy metabolism. While thiamine deficiency is commonly recognised in alcoholism, it can present in many other settings where it is often not considered and goes unrecognised. One challenging aspect to diagnosis is that it may have varied metabolic, neurological and cardiac presentations. Here we present an overview of the disorder, focusing on the multiple causes and clinical presentations. Interestingly, thiamine deficiency is likely increasing in frequency, especially among wildlife, where it is linked with changing environments and climate change. Thiamine deficiency should be considered whenever neurological or cardiological disease of unknown aetiology presents, especially in any patient presenting with lactic acidosis.

Pulmonary artery catheter usage in diagnosis of Shoshin beriberi presented with unexplained lactic acidosis.

Wet beriberi is a rare but fatal disease in modern society. The nonspecific clinical manifestations, including symptoms of heart failure and recalcitrant lactic acidosis, can prevent timely diagnosis. The use of a pulmonary artery catheter can promptly confirm a high cardiac output state and plays a crucial role in rapidly deteriorating cases. Appropriate treatment with intravenous administration of thiamine leads to dramatic recovery within hours. We present two cases of Shoshin beriberi, a fulminant variant of wet beriberi, diagnosed in 2016 and 2022 at our institute. The patients experienced haemodynamic collapse and refractory lactic acidosis, which were successfully diagnosed with the use of a pulmonary artery catheter and reversed by thiamine supplementation. We also reviewed 19 cases of wet beriberi reported between 2010 and 2022.

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes diagnosed after metformin-triggered stroke-like episodes.

A 40-year-old man with sensorineural hearing loss and diabetes mellitus was hospitalized with acute-onset impaired consciousness and clumsiness in his left hand. He had been taking metformin for 4 months. A neurological examination revealed confusion and weakness in the left upper limb. Increased lactate levels were detected in the serum and cerebrospinal fluid. Magnetic resonance imaging revealed lesions in the right parietal and bilateral temporal lobes with a lactate peak in magnetic resonance spectroscopy. Finally, we made a genetic diagnosis of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes based on the detection of m.3243A>G. It is well-known that metformin should not be administered in patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes because metformin inhibits mitochondrial function and triggers stroke-like episodes. However, our patient was diagnosed with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes after metformin administration. Thus, we encourage physicians to exercise caution in the prescription of metformin in patients with short stature, sensorineural hearing loss, or young-onset diabetes mellitus because these patients may have undiagnosed mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes.

Safety of metformin continuation in diabetic patients undergoing invasive coronary angiography: the NO-STOP single arm trial.

BACKGROUND: Despite paucity of data, it is common practice to discontinue metformin before invasive coronary angiography due to an alleged risk of Metformin-Associated Lactic Acidosis (M-ALA). We aimed at assessing the safety of metformin continuation in diabetic patients undergoing coronary angiography in terms of significant increase in lactate levels. METHODS: In this open-label, prospective, multicentre, single-arm trial, all diabetic patients undergoing coronary angiography with or without percutaneous coronary intervention at 3 European centers were screened for enrolment. The primary endpoint was the increase in lactate levels from preprocedural levels at 72-h after the procedure. Secondary endpoints included contrast associated-acute kidney injury (CA-AKI), M-ALA, and all-cause mortality. RESULTS: 142 diabetic patients on metformin therapy were included. Median preprocedural lactate level was 1.8 mmol/l [interquartile range (IQR) 1.3-2.3]. Lactate levels at 72 h after coronary angiography were 1.7 mmol/l (IQR 1.3-2.3), with no significant differences as compared to preprocedural levels (p = 0.91; median difference = 0; IQR - 0.5 to 0.4 mmol/l). One patient had 72-h levels ≥ 5 mmol/l (5.3 mmol/l), but no cases of M-ALA were reported. CA-AKI occurred in 9 patients (6.1%) and median serum creatinine and estimated glomerular filtration rate remained similar throughout the periprocedural period. At a median follow-up of 90 days (43-150), no patients required hemodialysis and 2 patients died due to non-cardiac causes. CONCLUSIONS: In diabetic patients undergoing invasive coronary angiography, metformin continuation throughout the periprocedural period does not increase lactate levels and was not associated with any decline in renal function. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov (NCT04766008).

The Association Between Hypophosphatemia and Lactic Acidosis After Cardiac Surgery With Cardiopulmonary Bypass: A Retrospective Cohort Study.

OBJECTIVES: The clinical significance of hypophosphatemia in cardiac surgery has not been investigated extensively. The aim of this study was to evaluate the association of postoperative hypophosphatemia and lactic acidosis in cardiac surgery patients at the time of intensive care unit (ICU) admission. DESIGN: A retrospective cohort study. SETTING: At a single academic center. PARTICIPANTS: Patients who underwent nontransplant cardiac surgery with cardiopulmonary bypass between August 2009 and December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum phosphate and lactate levels were measured upon ICU admission in patients undergoing nontransplant cardiac surgery with cardiopulmonary bypass. There were 681 patients in the low-phosphate (<2.5 mg/dL) group and 2,579 patients in the normal phosphate group (2.5-4.5 mg/dL). A higher proportion of patients in the low phosphate group (26%; 179 of 681; 95% CI: 23-30) had severe lactic acidosis compared to patients in the normal phosphate group (16%; 417 of 2,579; 95% CI: 15-18). In an unadjusted logistic regression model, patients in the low phosphate group had 1.9-times the odds of having severe lactic acidosis (serum lactate ≥4.0 mmol/L) when compared to patients in the normal phosphate group (95% CI: 1.5-2.3), and still 1.4-times the odds (95% CI: 1.1-1.7) after adjusting for several possible confounders. CONCLUSIONS: Hypophosphatemia is associated with lactic acidosis in the immediate postoperative period in cardiac surgery patients. Future studies will need to investigate it as a potential treatment target for lactic acidosis.