Persistent Lactic Acidosis Research Articles

7643 Acute blindness due to Metformin associated lactic acidosis

Abstract Disclosure: K.N. Pereira: None. K. Desai: None. T. Khan: None. S. Yong: None. Metformin, one of the most commonly prescribed oral hypoglycemic agents, effectively lowers basal and postprandial blood glucose. However, Metformin carries a black box warning for lactic acidosis, which is more common in setting of liver and kidney dysfunction. With an incidence rate of ∼ 4.3 cases per 100,000 patient-years, Metformin associated lactic acidosis (MALA) can present with nausea, vomiting, diarrhea, encephalopathy, hypothermia, respiratory failure and hypotension. Blindness is a rarely reported outcome of MALA. We present a case of a 48 year old intellectually disabled female with a history of type 2 diabetes (on Metformin) who presented with progressive encephalopathy insetting of intractable nausea and vomiting with poor oral intake, since starting lisinopril & rosuvastatin for newly diagnosed hypertension and hyperlipidemia. She was encephalopathic, hypothermic, hypotensive, tachycardic and tachypneic. Labs were notable for leukocytosis, AKI, hyperkalemia, elevated anion gap metabolic acidosis with a lactate of 13.6 and elevated lipase. She also tested positive for Influenza A. CT head showed no acute intracranial abnormality. CT chest, abdomen & pelvis was concerning for aspiration, multifocal pneumonia or a combination of both as well as acute interstitial pancreatitis. She was admitted to the ICU for further management including hemodialysis. She continued to have improving but persistent lactic acidosis despite multiple dialysis sessions. On day 5 of ICU stay, with resolution of her encephalopathy, she reported new onset complete bilateral painless vision loss. General eye and neurologic exam was unrevealing except for sluggishly reactive pupils to light. MRI brain showed an new acute 2 mm lacunar infarct in the right temporal lobe. Neurology ruled out stroke as the cause for her vision loss. Emergent ophthalmology evaluation revealed no retinopathy, macular edema, acute glaucoma or thromboembolic event. The new onset vision loss was suspected to be due to MALA due to persistent metabolic disturbances. Some animal studies have shown that retinal horizontal cells are sensitive to low pH, resulting in interruption of signal transmission to the visual neurons and consequent blindness. The presence of factors like metformin metabolites may contribute to impaired function of retinal cells.On extensive literature review it was noted that only 5 cases of vision loss associated with MALA have been reported. However, in these cases, vision loss was transient and reversed following correction of acidosis with dialysis. Our case highlights a rare consequence of MALA, which can be irreversible and cause lifelong disability. Presentation: 6/1/2024

THU368 A Rare Case Of Glycogenic Hepatopathy With Persistent Lactic Acidosis

Abstract Disclosure: M. Shah: None. S. Challagulla: None. Background: Glycogenic hepatopathy (GH) is an under-recognized complication of poorly controlled diabetes. It is caused by abnormal glycogen accumulation in hepatocytes leading to hepatomegaly and transient elevation of liver transaminases. Diagnosis is often delayed as liver biopsy is needed to distinguish it from other causes of liver injury. Complete resolution can be achieved with intensive glucose control. We present a case of GH diagnosed in a patient who developed increasing liver transaminases and persistent lactic acidosis after resolution of DKA. Clinical Case: We present a 21-year-old female with uncontrolled Type 1 diabetes who presented with fatigue, nausea, and generalized body aches. Patient was hemodynamically stable. Laboratory work up on admission showed a serum glucose of 834 mg/dL, serum bicarbonate less than 5 mEq/L, beta hydroxybutyrate was elevated to 8.7 mmol/L (normal <0.4 mmol/L), lactic acid was also elevated to 7.9 mmol/L (normal <2.0 mmol/L). She was diagnosed with DKA and treated with IV fluids and insulin drip. Over the next five days the patient’s symptoms improved and DKA resolved with beta hydroxybutyrate falling to <0.1 mmol/L. Her lactic acidosis however persisted, she had no apparent infection and no episodes of hypotension to explain this finding. CT scan of the abdomen revealed hepatomegaly not compatible with steatosis. Liver enzymes on admission were mildly elevated AST 57 IU/L and ALT 61 IU/L however values continued to rise and peaked at AST 2372 IU/L and ALT 681 IU/L five days later. Further laboratory studies revealed no evidence of viral hepatitis, no presence of drugs or toxins. Chronic liver disease work up revealed normal ANA, AMA, SPEP, ceruloplasmin, and iron levels. Patient ultimately underwent liver biopsy which revealed glycogenic hepatopathy, mild steatosis, and mild fibrosis. Patient’s lactic acidosis eventually improved with supportive care, and she was discharged. On follow up 3 months later the patient's liver enzymes had returned to normal. Discussion: Glycogenic hepatopathy is a rare diagnosis usually seen in patients with uncontrolled diabetes and elevated liver transaminases. It is hypothesized that pathogenesis of GH involves insulin increasing glycogen synthesis in the liver resulting in congested hepatocytes. Persistent lactic acidosis can also be seen; it has been proposed that increased insulin and dextrose administration prevents gluconeogenesis in the liver, therefore decreased conversion of pyruvate to glucose and increased lactate production. GH is important to understand and differentiate from other causes of liver injury and disease as treatment and prognosis is unique. Prompt liver biopsy should be pursued to elucidate diagnosis of GH. If patients are treated with aggressive glycemic control, hepatopathy can completely resolve. Presentation: Thursday, June 15, 2023

THU384 Too Sweet To Digest; A Case Of Persistent Lactic Acidosis Secondary To Glycogenic Hepatopathy

Abstract Disclosure: T. Ayub: None. L.A. Robles: None. F. Sami: None. S. Saleem: None. S. Guntupalli: None. Glycogenic hepatopathy (GH) is an under-recognized cause of persistent lactic acidosis and hepatomegaly in patients with uncontrolled DM and diabetic ketoacidosis (DKA). A 19-year-old female with history of type 1 DM with recurrent DKA presented with complaints of nausea, vomiting and abdominal pain for 1 week. Physical exam showed normal vitals and lower abdominal tenderness. Her initial labs showed glucose 250 mg/dl, high anion gap metabolic acidosis with beta hydroxy butyrate of 11.3 mmol/l, lactic acid 3.2mm/l, and mild transaminitis. She was diagnosed with DKA and started on insulin drip. Anion gap responded to IV insulin and fluid therapy and was transitioned to SQ insulin. However, she had increase in her lactic acid (8.2mm/l), without hemodynamic compromise, despite fluid resuscitation. Secondary work up including blood, urine, sputum cultures were non diagnostic for an infectious etiology. Abdominal imaging showed a liver span of 26 cm. There were no signs of end organ hypoperfusion, medication or toxin mediated insult as evident by normal transthoracic echo, iron studies, urine drug screen, alcohol level and negative hepatitis panel. Review of prior hospitalizations showed recurrent episodes of DKA with similar uptrend in lactic acid levels with negative secondary work up. Prior imaging revealed hepatomegaly during DKA episodes with resolution after strict glycemic control. Given uncontrolled DM type 1 with reversible and recurrent hepatomegaly, transaminitis, hyperlipidemia and elevated lactic acid, a clinical diagnosis of glycogenic hepatopathy was made. Patient declined liver biopsy due to concerns for complications. She was discharged on home insulin regimen with outpatient follow up. GH or hepatic glycogenosis is a reversible cause of lactic acidosis and hepatomegaly seen in uncontrolled DM type 1. Pathogenesis involves presence of fluctuating levels of hyperglycemia and insulin, concomitantly, that leads to glycogen storage. Insulin inhibits gluconeogenesis resulting in decreased conversion of pyruvate to glucose and high lactic acid levels, in the absence of any infectious, metabolic and hypoxic etiology. Lactic acidosis can be worsened when treated with high dose Insulin. Definite diagnosis of GH requires liver biopsy or gradient dual-echo MRI but can be made clinically in the setting of uncontrolled DM1, hepatomegaly, transaminitis and elevated lactic acid levels. Prompt recognition of GH can prevent unnecessary diagnostic testing and can decrease the duration of hospital stay. Treatment is strict glycemic control with resolution of condition and no long-term complications. Presentation: Thursday, June 15, 2023

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.

Mitochondrial toxicity induced by linezolid causing lactic acidosis

Linezolid-induced lactic acidosis is a rare, but life-threatening complication of a commonly used drug. Patients present with persistent lactic acidosis, hypoglycaemia, high central venous oxygen saturation and shock. Linezolid causes mitochondrial toxicity due to impaired oxidative phosphorylation. This is evidenced by cytoplasmic vacuolations in the myeloid and erythroid precursors of bone marrow smear as illustrated in our case. Discontinuation of the drug, administration of thiamine and haemodialysis reduces lactic acid levels.

Persistent Lactic Acidosis in an Infant With Milk Protein Allergy.

Persistent Lactic Acidosis in an Infant With Milk Protein Allergy.

Papillary Renal Cell Carcinoma with Massive Hemorrhage: An Autopsy Case Report

Abstract Introduction/Objective Spontaneous renal hemorrhage is a rare complication of various kidney pathologies. It can be due to renal artery aneurysms, arteriovenous malformations, cystic renal diseases, renal calculus, coagulation disorders, as well as neoplastic lesions like angiomyolipoma and renal cell carcinoma (RCC). Individuals present with sudden flank or scapular pain, hypovolemic shock, termed as Wunderlich syndrome (WS). 30-35% cases of WS are from spontaneously ruptured RCC, commonly clear cell variant (70%) followed by papillary (10-15%) and chromophobe variant (4-6%). We present an autopsy case of a papillary variant RCC identified as a small kidney mass with a pathogenetic correlation behind the intractable bleeding. Methods/Case Report An 81-year-old Caucasian man with a history of atrial fibrillation, on long-term Xarelto treatment, was found to have a 1.2 cm incidental mass in the right kidney. He started experiencing right-sided scapular pain, then rapidly became hypotensive, drowsy. CT scan revealed a large right-sided perinephric and retroperitoneal hematoma (17.5 x 5.7 x 8.9 cm) extending in the pelvis. Despite receiving blood products, other supportive treatment, and successful angio-embolization, his condition worsened to acute kidney injury, bowel ischemia, and persistent lactic acidosis leading to death. On autopsy, bloody ascites, clots on mesenteric root insertion, and bulging in retroperitoneal spaces were seen. The perinephric spaces had organized clots. The bleeding originated from a 2.0 x 2.0 cm brown mass in the middle pole of the right kidney. There was a slit-like vessel at the interface of the kidney and the mass. Microscopic examination of the mass shows trabecula of abnormal cells with abundant eosinophilic cytoplasm in the hemorrhagic and necrotic background. These cells are positive for PAX8, CK7, CD10, dim positive for CAIX, and negative for CD117, which is consistent with renal cell carcinoma, papillary variant. Results (if a Case Study enter NA) NA. Conclusion Papillary RCC is much less vascular and less aggressive than clear cell RCC. However, necrosis or bleeding into renal vessels may occur. In this case, blood-leaks and accumulation in enclosed space followed by necrosis, fibrosis, and hyalinization cause neovascularization forming a negative spiral for re-bleeding. Anticoagulants can lead to profuse sustained bleeding from even very small size RCC.

Abstract 10437: Venoarterial Extracorporeal Membrane Oxygenation Rescue Therapy in Vasoplegic Shock Due to Calcium Channel Blocker Overdose: 5 Year Single Center Experience

Introduction: Over 15,000 incidences of Calcium Channel Blocker (CCB) overdose were reported by the American Association of Position Control Centers (AAPCC) in 2020, resulting in 45 deaths from pure CCB overdose and 176 deaths from multidrug overdose involving CCBs. We present a single-center experience on the use of VA ECMO in the management of refractory hypotension due to CCB toxicity. Hypothesis: VA ECMO is effective and can be life-saving in vasoplegic shock from drug overdose Methods: We retrospectively reviewed our ECMO registry in the last 5 years to identify patients who were started on ECMO support for refractory hypotension due to drug overdose. Results: We found 5 patients who were started on VA-ECMO for drug overdose, all involving CCBs. Mean age was 60. They had persistent lactic acidosis and hypotension after fluid resuscitation, requiring escalating doses of vasopressors until they were on or near the maximum. All patients were started on hyperinsulinemia euglycemic protocol and 3 patients received methylene blue. The mean time to intubation was 11.2 ± 4.14 hours. An echocardiogram demonstrated intact systolic function in all patients. VA-ECMO was started within 11.2 ± 4.5 hours of admission. Pressor requirements quickly improved on ECMO support. Average time on ECMO was 69 ± 48.6 hours. 4 of 5 patients improved quickly and were extubated within 10 days (mean: 4.88 ± 2.95). In these 4 patients, the length of ICU stay was 8.5 ± 3.87 days, and hospital stay was 11.75 ± 2.06 days. One patient had a protracted course due to renal failure, pneumonia, and concern for North-South Syndrome. Cannulation was switched to subclavian/axillary approach, but that was complicated by left arm ischemia and switch to VV-ECMO after 44 hours of VA-ECMO. She was discharged after a 46-day hospital stay. Conclusions: VA-ECMO support is effective and lifesaving in patients with refractory shock from CCB toxicity. Early referral to ECMO capable center should be considered in these patients.

Clinical and genetic spectrum of mitochondrial DNA depletion syndromes: A report of 6 cases with 4 novel variants

Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are a heterogeneous group of rare autosomal recessive genetic disorders characterized by a decrease in the number of mtDNA copies inside the organ involved. There are three distinct forms of MDS including the hepatocerebral, the myopathic and the encephalomyopathic forms. The diversity in the clinical and genetic spectrum of these disorders makes the diagnosis challenging. Here, we describe the clinical phenotype and the genetic spectrum of 6 patients with MDS including 4 novel variants and compare them with previously reported cases. Subject and MethodsSix patients from six unrelated families were included in this study. All the patients were subjected to a detailed history, thorough general and neurologic examination, basic laboratory investigations including lactic acid and ammonia, amino acids, acylcarnitine profiles and brain MRI. Whole-exome sequencing was performed for all of them to confirm the suspicion of mitochondrial disorder. ResultsIn our series, four patients presented with the hepatocerebral form of MDS with the major presenting manifestation of progressive liver cell failure with severe hypotonia and global developmental delay. Four variants in the DGUOK gene and the MPV17 have been identified including 2 novel variants. One patient was identified in the myopathic form presenting with myopathy associated with two novel variants in the TK2 gene. One patient was diagnosed with encephalomyopathic form presenting with persistent lactic acidosis and global delay due to a homozygous variant in the FBXL4 gene. ConclusionMDS has a wide spectrum of heterogeneous clinical presentations and about nine different genes involved. Whole exome sequencing (WES) has resulted in faster diagnosis of these challenging cases as the phenotype overlap with many other disorders. This should be considered the first-tier diagnostic test obviating the need for more invasive testing like muscle biopsies.

Effects of Occult Hypoperfusion on Local Circulation and Inflammation - An Analysis in a Standardized Polytrauma Model.

IntroductionOccult hypoperfusion (OH) is defined as persistent lactic acidosis despite normalization of vital parameters following trauma. The aim of this study was to analyze the association of occult hypoperfusion with local circulation and inflammation of injured soft tissue in a porcine polytrauma model.MethodsThis experimental study was performed with male landrace pigs who suffered a standardized polytrauma, including a femoral fracture, blunt chest trauma, liver laceration and a mean arterial pressure (MAP) controlled hemorrhagic shock. One hour after induction of trauma, the animals were resuscitated with retrograde femoral nailing, liver packing and volume replacement. Animals were stratified into Group Norm (normalizing lactate levels after resuscitation) and Group occult hypoperfusion (OH) (persistent lactate levels above 2 mmol/l with normalizing vital parameters after resuscitation). Local circulation (oxygen saturation, hemoglobin amount, blood flow) was measured with optical sensors at the subcutaneous soft tissue at the fractured extremity as well as at the stomach and colon. Local inflammatory parameters [interleukin (IL) 6, 8, 10, and heat shock protein (HSP)] were analyzed in the subcutaneous tissue of the fractured extremity.ResultsGroup Norm (n = 19) and Group OH (n = 5) were comparable in baseline vital and laboratory parameters. The shock severity and total amount of blood loss were comparable among Group Norm and Group OH. Following resuscitation Group OH had significantly lower local relative hemoglobin amount at the injured soft tissue of the fractured extremity when compared with Group Norm (39.4, SD 5.3 vs. 63.9, SD 27.6 A.U., p = 0.031). The local oxygenation was significantly lower in Group OH compared to Group Norm (60.4, SD 4.6 vs. 75.8, SD 12.8, p = 0.049). Local IL-6 in the fatty tissue was significantly higher in Group OH (318.3, SD 326.6 [pg/ml]) when compared with Group Norm (73.9,SD 96.3[pg/ml], p = 0.03). The local circulation at the abdominal organs was comparable in both groups.ConclusionOH is associated with decreased local circulation and increased local inflammation at the injured soft tissue of the extremity in polytrauma. OH might reflect the severity of local soft tissue injuries, and guide treatment strategies.

EP457: Fetal presentation of pyruvate dehydrogenase complex deficiency diagnosed by prenatal exome sequencing

Pyruvate dehydrogenase complex deficiency is a rare X-linked inborn error of metabolism that typically presents in infancy or early childhood, rather than prenatally. The mean age of diagnosis is ∼45 months (median age of diagnosis is ∼20 months of age). Affected individuals have persistent lactic acidosis, which causes a variety of neurological manifestations. Progressive neurological deterioration is often accompanied by encephalopathy, seizures, and death. We present a prenatal case of pyruvate dehydrogenase complex deficiency diagnosed by prenatal exome sequencing, which presented with multiple nonspecific congenital anomalies.

A rare case of B-cell lymphoma characteristic of persistent lactic acidosis, hypoglycemia, and dyslipidemia in the emergency department

A rare case of B-cell lymphoma characteristic of persistent lactic acidosis, hypoglycemia, and dyslipidemia in the emergency department

Складнощі діагностики рідкісної вродженої мітохондріальної патології — комбінованого дефіциту окисного фосфорилювання 26-го типу в дитини раннього віку: клінічний випадок

Hereditary mitochondrial diseases are a consequence of congenital errors in energy metabolism with very variable and predominantly multisystem manifestations, they require differential diagnosis with a wide range of phenotypically similar nosologies, and their verification is a complex problem with a need of a multidisciplinary approach. The article describes a rare clinical case diagnosed in a girl of early age of a congenital mitochondrial pathology with autosomal recessive inheritance — a combined oxidative phosphorylation deficiency of type 26 (COXPD-26) due to two mutations in the heterozygous state of the TRMT5 gene (tRNA methyltransferase 5) on the chromosome 14q23. The patient's illness was accompanied by a debut from birth and was characterized by insufficient weight gain, manifestations of cardiomyopathy, repeated intercurrent infectious diseases with increased activity of blood transaminases, creatine kinase-MB, hepatopathy with hypoalbuminemia, convulsive syndrome, intolerance to valproic acid, progressive delay in stato-kinetic and psychoverbal development, that is, the symptomatology was characterized by progression, multisystem character with predominant damage to the heart, liver and nervous system. The diagnostic algorithm for mitochondrial diseases is one of the most complex in medical practice. In young children, persistent or progressive multisystem disorder of unknown etiology, unknown multiple complex neurological manifestations or neurological monosymptom with involvement of other systems, less often — specific clinical symptoms; persistent lactic acidosis, other positive or questionable laboratory screening findings are suspicious of probable mitochondrial pathology. Numerous hospitalizations, repeated consultations by different specialists, multiple additional labtests, and multiple conflicting diagnoses may indicate a possible mitochondrial pathology. Only whole exome sequencing of a blood sample with an analysis of variations in the number of copies of genes and genomic sequencing of a new generation with targeted genetic testing made it possible to diagnose in a child a hereditary metabolic disorder from the group of defects in the mitochondrial respiratory chain — a combined deficiency of oxidative phosphorylation type 26, previously described in only a few patients. The research was carried out in accordance with the principles of the Helsinki declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: mitochondrial pathology, combined deficiency of oxidative phosphorylation of type 26 (COXPD-26), clinical case.

Machine Learning Consensus Clustering Approach for Patients with Lactic Acidosis in Intensive Care Units.

Background: Lactic acidosis is a heterogeneous condition with multiple underlying causes and associated outcomes. The use of multi-dimensional patient data to subtype lactic acidosis can personalize patient care. Machine learning consensus clustering may identify lactic acidosis subgroups with unique clinical profiles and outcomes. Methods: We used the Medical Information Mart for Intensive Care III database to abstract electronic medical record data from patients admitted to intensive care units (ICU) in a tertiary care hospital in the United States. We included patients who developed lactic acidosis (defined as serum lactate ≥ 4 mmol/L) within 48 h of ICU admission. We performed consensus clustering analysis based on patient characteristics, comorbidities, vital signs, organ supports, and laboratory data to identify clinically distinct lactic acidosis subgroups. We calculated standardized mean differences to show key subgroup features. We compared outcomes among subgroups. Results: We identified 1919 patients with lactic acidosis. The algorithm revealed three best unique lactic acidosis subgroups based on patient variables. Cluster 1 (n = 554) was characterized by old age, elective admission to cardiac surgery ICU, vasopressor use, mechanical ventilation use, and higher pH and serum bicarbonate. Cluster 2 (n = 815) was characterized by young age, admission to trauma/surgical ICU with higher blood pressure, lower comorbidity burden, lower severity index, and less vasopressor use. Cluster 3 (n = 550) was characterized by admission to medical ICU, history of liver disease and coagulopathy, acute kidney injury, lower blood pressure, higher comorbidity burden, higher severity index, higher serum lactate, and lower pH and serum bicarbonate. Cluster 3 had the worst outcomes, while cluster 1 had the most favorable outcomes in terms of persistent lactic acidosis and mortality. Conclusions: Consensus clustering analysis synthesized the pattern of clinical and laboratory data to reveal clinically distinct lactic acidosis subgroups with different outcomes.

Persistent Lactic Acidosis after resolution of DKA in Young Patients with Poorly Controlled Diabetes Mellitus

Persistent Lactic Acidosis after resolution of DKA in Young Patients with Poorly Controlled Diabetes Mellitus

TRMU deficiency: A broad clinical spectrum responsive to cysteine supplementation

TRMU is a nuclear gene crucial for mitochondrial DNA translation by encoding tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase, which thiolates mitochondrial tRNA. Biallelic pathogenic variants in TRMU are associated with transient infantile liver failure. Other less common presentations such as Leigh syndrome, myopathy, and cardiomyopathy have been reported. Recent studies suggested that provision of exogenous L-cysteine or N-acetylcysteine may ameliorate the effects of disease-causing variants and improve the natural history of the disease. Here, we report six infants with biallelic TRMU variants, including four previously unpublished patients, all treated with exogenous cysteine. We highlight the first report of an affected patient undergoing orthotopic liver transplantation, the long-term effects of cysteine supplementation, and the ability of the initial presentation to mimic multiple inborn errors of metabolism. We propose that TRMU deficiency should be suspected in all children presenting with persistent lactic acidosis and hypoglycemia, and that combined N-acetylcysteine and L-cysteine supplementation should be considered prior to molecular diagnosis, as this is a low-risk approach that may increase survival and mitigate the severity of the disease course.

Advances in Diagnosis of Mitochondrial Diseases: Case Report of an Infant with Pearson Syndrome

Pearson syndrome (PS) is a mitochondrial disorder that presents in early infancy as a multisystemic disease affecting the bone marrow and pancreas. It may present with anemia, diarrhea, exocrine pancreatic dysfunction, and failure to thrive.[1] Delay in diagnosis can lead to severe morbidity and mortality in infancy. We report the case of a 9-month-old presenting with failure to thrive, severe macrocytic anemia and pancytopenia initially thought to have gastroesophageal reflux and feeding intolerance. Severe macrocytic anemia and pancytopenia prompted an early bone marrow evaluation. Abnormal bone marrow findings including vacuolated marrow precursors and ringed sideroblasts along with persistent mild lactic acidosis led to a rapid and extensive genetics workup. Whole exome sequencing including mitochondrial genome sequencing detected a 2.3 kb heteroplasmic deletion in m.12113_14421 encompassing the MT-ND5 gene consistent with the diagnosis of Pearson Syndrome. This case report highlights the advances in molecular genetic testing to diagnose patients with complex medical histories along the spectrum of mitochondrial diseases and the importance of early diagnosis to start treatment.

Severe type-B lactic acidosis in a patient with bilateral renal Burkitt's lymphoma.

Introduction: Lactic acidosis (LA) can be categorized as type A, which occurs in the presence of tissue hypoxia, or type B, occurring in the absence of tissue hypoxia. Hematologic malignancies are an uncommon cause of type B LA. Case presentation: A 63-year-old man, HIV-negative, with a history of diabetes mellitus, hypothyroidism, and non‐alcoholic fatty liver disease (NAFLD), presented to the ED complaining of acute-on-chronic lumbar pain, and was found to have high serum anion gap (AG) LA. The rest of chemistry and infectious workup was within normal limits. Despite bicarbonate therapy and fluid resuscitation, the patient remained with persistent AG metabolic acidosis and increasing lactic acid up to 14.5 mmol/L. An abdominal computerized tomography (CT) revealed multiple bilateral enhancing lesions in the kidneys, as well as gastric wall thickening. Upper gastrointestinal endoscopy with biopsy showed a high-grade Burkitt’s lymphoma. Further staging showed bone marrow involvement and extensive abdominal adenopathy. After two cycles of inpatient chemotherapy with dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab), the patient developed multifocal pneumonia complicated by respiratory failure. Following a prolonged ICU stay, after discussion with the family members, a decision of withdrawal of life-sustaining therapy was reached. Conclusion: Persistent LA, without identifiable causes of tissue hypoxia, should prompt clinicians to suspect non-hypoxic etiologies, including occult high-grade malignancies. Hematological malignancies constitute an extremely rare cause of type-B LA, carrying a poor prognosis.

206. The Utility of Lactate as a Biomarker for Sepsis in Cancer Patients

BackgroundSerum lactate is included in the initial assessment of patients with sepsis. However, cancer patients develop lactic acidosis for a variety of reasons and are underrepresented in most studies. Therefore, elevated lactate levels may lead to overdiagnosis of sepsis and excessive antibiotic use. The purpose of this study is to evaluate the utility of lactate as a biomarker for sepsis in cancer patients. The primary endpoint is the rate of 24-hour lactate clearance between infectious and non-infectious causes of lactic acidosis in cancer patients. Secondary objectives explore the duration of antibiotic therapy (DOT), the impact of liver metastasis on serum lactate levels, and the role of procalcitonin in distinguishing between infectious and non-infectious causes of lactic acidosis.MethodsRetrospective chart review by Antimicrobial Stewardship teamFigure 1: Study design ResultsPreliminary data from a random subset of our sample (45/150) suggests there is no difference in mean serum lactate levels between infectious and non-infectious groups (4.6 vs 6.4). However, a substantial difference exists in the rate of 24h lactate clearance, although the difference was not statistically significant (58.3% vs 33%; p=0.13) (Fig2). There was a significant difference in antibiotic DOT (12.6 vs 3.3; p< 0.0001) presumably due to robust antimicrobial stewardship practices. Consistent with previous studies, there was a significant difference in procalcitonin levels between groups (27.2 vs 1.5, p=0.04).A sub-analysis of non-infectious patients with liver metastasis revealed a statistically significant difference in the rate of lactate clearance (21% vs 61.5%, p=0.03) (Fig3) suggesting that liver involvement impacts lactate clearance. Antibiotic DOT were also longer in non-infectious patients with liver metastasis (4.53 vs 1.38, p=0.02).Comparing end points between cancer patients with and witthout infection. Liver involvement affecting Lactate clearance in patients without infection. ConclusionCancer patients often manifest SIRS criteria at baseline which may lead to the overdiagnosis of infection and excessive antibiotic usage. Our observation is that lactate clearance as opposed to degree of lactic acidosis may be a more accurate indicator of infection in cancer patients especially those with liver involvement. This information may mitigate unnecessary antibiotic use in cancer patients with persistent lactic acidosis unrelated to infection.Disclosures All Authors: No reported disclosures

Bilateral Renal Burkitt Lymphoma Presenting with Persistent Lactic Acidosis in an HIV-Negative Patient

Bilateral Renal Burkitt Lymphoma Presenting with Persistent Lactic Acidosis in an HIV-Negative Patient