Lactic Acidosis Research Articles

Approach To Poisoned Patients with High Anion Gap Metabolic Acidosis in The Emergency Department – A Case Series

Toxicology cases are frequent presentations in the emergency department (ED) and often their presentation can vary from a straightforward manner to a complex manner. In this case series we will discuss three cases that presented to the emergency department with a known, suspected, and unknown toxicological substance ingestion with the common denominator being high anion gap metabolic acidosis (HAGMA). High Anion Gap Metabolic acidosis is a subcategory of metabolic acidosis. Categorizing metabolic acidosis as high anion gap aids in identifying the underlying disease process and subsequently initiating appropriate treatment. There have been many broadly inclusive mnemonics used to list the common causes of High anion gap acidosis such as CAT MUDPILES which correspond to Carbon monoxide, Cyanide, Congenital heart disease, Aminoglycosides, Theophylline, Toluene, Methanol, Uremia, Diabetic ketoacidosis, Alcoholic ketoacidosis, Starvation, Acetaminophen, Phenformin, Paraldehyde, Iron, Isoniazid, Inborn errors of metabolism, Lactic acidosis, Ethanol, Ethylene glycol and Salicylates respectively. It is not uncommon to be faced with patients with an unclear clinical picture and a lack of clear toxicological ingestion. In such circumstances, the presence of a high anion gap acidosis is an important clue that should prompt investigating for uncommon toxicological causes not listed in the forementioned mnemonics, such as metformin, beta blockers and calcium channel blockers.

Comparative Analysis of Metformin and Imeglimin: Exploring Therapeutic Implications

The landscape of type 2 diabetes mellitus (T2DM) management is evolving with the emergence of imeglimin alongside the longstanding use of metformin. While both drugs share structural similarities and target mitochondrial complex I, they exhibit distinct mechanisms of action and therapeutic effects. Imeglimin, with its mitochondrial modulation and competitive inhibition of complex I, holds promise in mitigating beta-cell dysfunction, improving insulin sensitivity, and offering potential cardiovascular benefits. Efficacy studies suggest comparable outcomes with metformin, underscoring the utility of imeglimin as a valuable addition to the T2DM armamentarium. There is mixed evidence on the cardio-renal benefits of metformin while imeglimin’s tissue-protective effects in preclinical studies offer a glimpse into potential cardiovascular advantages. Studies suggest imeglimin’s superior gastrointestinal tolerability. Imeglimin’s potential as an anti-diabetic agent is further underscored by its diverse combination options. In clinical practice, metformin remains a cornerstone in the management of T2DM. Imeglimin, with its lesser gastrointestinal side effects and theoretically lower risk of lactic acidosis, offers a compelling alternative, particularly in patients intolerant to metformin. With preliminary signs pointing toward potential cardiovascular and renal benefits of imeglimin, exploring its application in patients with atherosclerotic cardiovascular disease presents an enticing prospect. As the field advances, adopting a nuanced and personalized approach to T2DM management could lead to imeglimin carving out a significant niche in the dynamic landscape of diabetes therapeutics.

Induced Ruminal Lactic Acidosis in Sheep Treated with Various Remedial Agents in Libo Kemkem Districts, Northwest Ethiopia.

Grain overload is a ruminant metabolic disorder associated with overingestion or a sudden change to rapidly fermentable concentrate feeds. A randomized clinical trial was carried out in Libo Kemkem districts to investigate vital signs, ruminal fluid, and hematological changes in sheep related to grain overload and to assess the treatment efficacy of various remedial agents in Farta sheep breeds. All sheep were selected by using the simple random process, and categorized into four groups of eight animals groups I, II, and III in which each sheep was given 80 g of wheat flour per kg of body weight then baking soda, Magnalax, and digestive powder were treated successively, but group IV was the negative control group. The current clinical trial explained that all acidotic sheep had statistically significant (p < 0.0002) lower body temperature, rumen motility, protozoa activity, and ruminal fluid pH with 38.48 ± 0.20, 0.5 ± 0.89, 6 (75%), and 5.37 ± 0.34 mean value successively. Nevertheless, there were significant (p < 0.0059) increments in hematological variables including total red blood cell, total white blood cell, packed cell volume, and hemoglobin estimation with 14.05 ± 1.27, 12.71 ± 0.99, 40.78 ± 5.24, and 14.78 ± 1.83 mean value, respectively, before treatment in acidotic sheep. There were also vital sign increments including pulse rate, respiratory rate, skin turgor, and capillary refill time with 123.5 ± 27.1, 73.75 ± 12.71, 3 ± 1.78, and 3.37 ± 1.77 mean values, respectively, before medical treatment in acidotic sheep. Digestive powder was the first drug of choice, followed by Magnalax, and baking soda was ranked at the end based on clinical recovery. The treatment effectiveness illustrated that all treatments could cure the grain overload. Nevertheless, digestive powder is the drug of choice based on the clinical and systemic recovery of the sheep. In addition to this, sheep should be introduced gradually to concentrate rations over 2-3 weeks with a mixture of concentrate in the milled feed containing roughage.

Diffuse Large B-cell Lymphoma with Severe Lactic Acidosis and Liver Failure: A Case Report and Literature Review.

Among causes of liver failure, liver failure due to lymphocytic infiltration is rare. Unlike typical liver failure, some cases present with severe lactic acidosis and a poor prognosis. We herein report a case of diffuse large B-cell lymphoma with severe lactic acidosis and liver failure. We further discuss the characteristics of similar cases in the literature, suggesting that intrahepatic infiltration by hematological malignant cells should be considered as a differential diagnosis in the presence of severe lactic acidosis and liver failure. This study underscores the importance of early recognition and serves as a reference for future cases.

Metformin toxicity in the intensive care unit: A case series and review of the literature.

Metformin toxicity is a life-threatening condition with high morbidity and mortality. Toxicity predominantly occurs in the setting of acute renal dysfunction, as the drug is solely eliminated by the kidneys. While this risk is widely known to clinicians, diagnosing metformin toxicity is challenging because commercially available serum metformin levels require days to weeks to result. Therefore, the intensivist must rely on medical history, clinical presentation, and routine laboratory findings to make the preliminary diagnosis. Treatment of metformin toxicity includes supportive fluid hydration, vasopressors, and emergent hemodialysis (HD). We report three critically ill patients who had near-fatal severe metformin-induced lactic acidosis. Their metformin levels were markedly higher than the toxicity threshold reported by the Federal Drug Agency. These patients made a prompt and complete recovery after the initiation of HD. We also review the pathophysiology, clinical presentation, diagnosis, and treatment of metformin toxicity.

Analysis of Metformin-Associated Lactic Acidosis using the Japanese Adverse Drug Event Report Database

Analysis of Metformin-Associated Lactic Acidosis using the Japanese Adverse Drug Event Report Database

Rapid Resolution of Metformin-Induced Lactic Acidosis with Continuous Haemodiafiltration: A Case Report

Rapid Resolution of Metformin-Induced Lactic Acidosis with Continuous Haemodiafiltration: A Case Report

Linezolid Induced Lactic Acidosis: A Case Report and Literature Review of a Rare Side Effect

Linezolid Induced Lactic Acidosis: A Case Report and Literature Review of a Rare Side Effect

Exploring the Potential of Ribes nigrum L., Aronia melanocarpa (Michx.) Elliott, and Sambucus nigra L. Fruit Polyphenol-Rich Composition and Metformin Synergy in Type 2 Diabetes Management.

Type 2 diabetes, characterized by insulin resistance and impaired glucose homeostasis, is commonly managed through lifestyle interventions and medications such as metformin. Although metformin is generally well-tolerated, it may cause gastrointestinal adverse effects and, in rare cases, precipitate lactic acidosis, necessitating cautious use in individuals with renal dysfunction. Additionally, concerns regarding its impact on hepatic function have led to its discontinuation in cirrhotic patients. This study explores the potential synergistic benefits of a polyphenol-rich blend containing black currant, chokeberry, and black elderberry extracts alongside metformin in managing type 2 diabetes. In vitro results highlighted distinct effects of AMPK pathway modulation, showcasing reductions in cholesterol and triglyceride levels alongside a notable enhancement in glucose uptake. The blend, when combined with metformin, significantly reduced insulin levels and fasting glucose concentrations in an in vivo model. Furthermore, hepatic analyses unveiled a modulation in cellular pathways, suggesting a potential influence on lipid metabolism, attenuation of inflammatory pathways, a decrease in cellular stress response, and antioxidant defense mechanisms, collectively implying a potential reduction in liver fat accumulation. The findings suggest a potential complementary role of polyphenols in enhancing the efficacy of metformin, possibly allowing for reduced metformin dosage and mitigating its side effects. Further clinical studies are warranted to validate these findings and establish the safety and efficacy of this nutraceutical approach in managing type 2 diabetes.

Acute Precipitated Opioid Withdrawal With Akathisia, Delirium, and Lactic Acidosis from Low-Dose Naltrexone for Chronic Pain: Case Report

BACKGROUND: Low-dose naltrexone (LDN) is an increasingly popular medication to enhance analgesia and decrease opioid reliance in patients with chronic pain. CASE REPORT: We present the case of a 66-year-old man on long-term opioids for chronic pain who was initiated on 1 mg of LDN for enhanced analgesia and subsequently went into severe precipitated opioid withdrawal (POW), a reaction understood to be rare at such low doses. CONCLUSION: LDN has been introduced into pain medicine as a safe and effective adjunct for the treatment of chronic pain conditions in both opioid-naive patients and those on concomitant opioid therapy. While this is generally considered a safe practice, LDN initiation can cause acute precipitated withdrawal in certain individuals already on opioids, even at low doses previously thought to be free from this risk. We recommend pain providers consider this effect and be prepared to manage POW when prescribing LDN. KEY WORDS: Low-dose naltrexone, LDN, chronic pain, precipitated opioid withdrawal, case report

Bariatric surgery and changes in metformin distribution: about a fatal case

A 65 year-old woman, suffering from mellitus type 2 diabetes and obesity, died at home, three days after bariatric surgery (Roux-en-Y gastric by-pass: RYGB). Her treatment, including metformin and dapagliflozin, was stopped before surgery and not postoperatively reinstalled. A forensic autopsy, toxicological and histological analyses were performed.No macroscopic or microscopic evidence of digestive perforation or peritonitis was identified, excluding an early surgery complication as the cause of death. Toxicological analysis revealed the presence of Metformin in all matrices tested, with a potentially fatal blood concentration. Death was attributed to lactic acidosis caused by a metformin overdose. With no evidence for suicide by ingestion of metformin, the authors supposed that the bariatric surgery might have caused changes in the absorption of metformin, leading to a rapid overdose and death. The only study in the literature on this subject, demonstrated a significant increase in the bioavailability of metformin following oral administration in gastric bypass patients. Thus, it can be anticipated that a therapeutic dose can become toxic when administrated to a subject who recently modified her digestive equipment. As this represents the first case of metformin overdose following bariatric surgery, further cases will be needed to confirm our initial observations.

Microbleeds within Mitochondrial Stroke-Like Lesion Rather Result from Their Vulnerability Than from Microangiopathy

MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like episode) is one of the most common syndromic mitochondrial disorders (MID) and is due to the variant m.3243A&gt;G in MT-TL1 in approximately 80% of cases. MELAS is a multisystem disorder with stroke-like episodes (SLEs) as a pathognomonic feature. The morphological correlate of SLEs in cerebral imaging are stroke-like lesions (SLLs). SLLs present on cerebral MRI with a T2, FLAIR, DWI, and PWI-hyperintense and OEF-hypointense lesion that is not confined to a vascular territory and extends to a nadir before disappearing or terminating as a structural lesion. Occasionally, these features are accompanied by microbleeds within the SLL, usually along the cortex. These microbleeds are thought to result from laminar cortical necrosis, and end-stage of a SLL or seizures, a common manifestation of SLEs.

Hypertrophic cardiomyopathy and lactic acidosis in a child with acyl-CoA dehydrogenase 9 deficiency. Review of the literature and clinical observation

Introduction. Acyl-CoA dehydrogenase 9 deficiency (mitochondrial complex I deficiency) is an autosomal recessive disease from the heterogeneous group of disorders of mitochondrial β-oxidation of fatty acids caused by mutations in the ACAD9 gene. The disease is characterized by a wide range of clinical manifestations, the most common of which are metabolic acidosis, hypertrophic cardiomyopathy, muscle hypotonicity, and impaired motor skills. The article presents the first Russian clinical observation of a rare variant of hypertrophic cardiomyopathy with early debut in a patient with mitochondrial complex I deficiency caused by homozygous mutation c.659C&gt;T (p.A220V) in the ACAD9 gene and emphasizes the importance of early diagnosis of the disease and complex drug therapy to prevent the development of severe complications.&#x0D; Objective: to describe the clinical course and management of a patient with the pathogenic c.659C&gt;T (p.A220V) variant of the ACAD9 gene.&#x0D; Detailed analysis of anamnesis data, results of clinical, laboratory, instrumental diagnostic methods, and molecular genetic research performed using high-throughput sequencing and direct Sanger sequencing technology. &#x0D; The article presents a literature review and detailed data on clinical observation of a child with homozygous c.659C&gt;T (p.A220V) mutation in the ACAD9 gene diagnosed on the basis of the cardiology department of the National Medical Research Center for Children’s Health. Early disease markers and possibilities of complex drug therapy to prevent the development of severe complications are described.&#x0D; Conclusion. Disruption of mitochondrial beta-oxidation of fatty acids is a heterogeneous group of inherited diseases due to abnormal mitochondrial beta-oxidation and transport of carnitine and fatty acids in mitochondria. A feature of these diseases is the multisystem nature of the lesion and its progressive course. In some cases, the initial clinical manifestations may be various disorders of the cardiovascular system (cardiomyopathy, heart rhythm disturbances), which may cause death in neonatal period and early childhood. Early molecular genetic research provides accurate diagnosis and, accordingly, timely prescription of complex therapy.

The significance of admission blood lactate and fibrinogen in pediatric traumatic brain injury: a single-center clinical study

BackgroundTraumatic brain injury (TBI) is a significant cause of morbidity and mortality in pediatric patients, leading to long-term physical, cognitive, and psychological impairments. Blood lactate and fibrinogen levels have emerged as potential biomarkers associated with tissue hypoperfusion and coagulation dysfunction, respectively. However, limited research has specifically focused on the significance of these biomarkers in pediatric TBI. This study aimed to investigate the clinical significance of blood lactate and fibrinogen levels upon admission in pediatric patients with traumatic brain injury.MethodsThe medical records of 80 children with a traumatic brain injury who were admitted from January 2017 to January 2021 were retrospectively analyzed. The two groups were compared according to whether the blood lactate in the admission arterial blood gas increased and the fibrinogen content in the coagulation function decreased. The clinical data of the children in the two groups were different, and then they were divided into a good prognosis group and a poor prognosis group according to the GOS prognostic score, and the differences in the clinical indicators of the two groups were compared.ResultsAmong the 80 patients, 33 had elevated blood lactate levels, 34 had decreased fibrinogen levels, and 29 had an unfavorable outcome (GOS < 4). Compared to the normal blood lactate group, there were no statistically significant differences in age, sex ratio, or platelet count in the elevated blood lactate group (P > 0.05). However, the elevated blood lactate group had lower Glasgow Coma Scale (GCS) scores upon admission, higher blood lactate levels, lower fibrinogen levels, longer hospital stay, lower GOS scores, and a higher proportion of GOS < 4 (P < 0.05). Compared to the normal fibrinogen group, there were no statistically significant differences in age, sex ratio, or platelet count in the decreased fibrinogen group (P > 0.05). However, the decreased fibrinogen group had lower GCS scores upon admission, higher blood lactate levels, lower fibrinogen levels, longer hospital stays, lower GOS scores, and a higher proportion of GOS < 4 (P < 0.05). Compared to the favorable outcome group, there were no statistically significant differences in age, sex ratio, or platelet count in the unfavorable outcome group (P > 0.05). However, the unfavorable outcome group had lower GCS scores upon admission, higher blood lactate levels, lower fibrinogen levels, longer hospital stays, a higher incidence of pulmonary infection, a higher incidence of stress ulcers, and lower GOS scores (P < 0.05).ConclusionThe levels of blood lactate and fibrinogen may represent the severity of children with traumatic brain injury and may be risk factors for poor prognosis of children with traumatic brain injury.

Epilepsy and MELAS syndrome: literature review and clinical observation

MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) belongs to the group of mitochondrial diseases. Most MELAS syndrome cases are associated with the A3243G mutation in the MTTL1 gene. A common clinical manifestation of the syndrome is presented by epileptic seizures (ES) characterized by phenotypic polymorphism and resistance to antiepileptic therapy. Diagnosis and treatment of epilepsy in patients with MELAS syndrome often poses difficulties. We present a clinical case of adult patient with MELAS syndrome with identified A3243G mutation and epilepsy. The disease course developed to severe cognitive impairment. The first focal ES occurred during stroke-like episode. Further seizures were observed spontaneously, with high frequency, often manifested as a series. Focal ES often had blurred polymorphic manifestations. The choice of drug therapy took into account the side effects of antiepileptic drugs (AEDs) including potentially mitochondria-related negative effects. While diagnosing EP in MELAS syndrome, it should be considered that seizures often occur during stroke-like episodes and may have blurred polymorphic clinical manifestations. Cognitive impairment in patients complicates ES detection. First-line drugs should be presented by AEDs with low mitochondrial toxicity.

Severe perioperative lactic acidosis in a pediatric patient with glycogen storage disease type Ia: a case report

BackgroundGlycogen storage disease (GSD) is a group of rare inherited metabolic disorders caused by enzyme deficiencies in glycogen catabolism. GSD type Ia is a congenital deficiency of the enzyme responsible for the final step in glucose production by glycolysis, resulting in impaired carbohydrate metabolism.Case presentationA 14-year-old boy with GSD type Ia was scheduled for a maxillary cystectomy under general anesthesia. He was taking oral sugars such as uncooked cornstarch regularly to prevent hypoglycemia. Perioperatively, glucose was administered via the peripheral vein for fasting; however, severe lactic acidosis occurred. He also developed hypercapnia because of intraoperative poor ventilation caused by hepatomegaly.ConclusionsWe experienced a child with GSD type Ia who developed severe lactic acidosis despite continuous glucose infusion. Further studies are required to determine appropriate perioperative management for patients with GSD, including fasting glucose administration.

Prehospital blood gas analyses in acute patients treated by a ground-based physician-manned emergency unit: a cohort study

BackgroundThe prehospital patients treated by ambulances and mobile emergency care units (MECU) are potentially critically ill or injured. Knowing the risks of serious outcomes in these patients is important for guiding their treatment. Some settings allow for prehospital arterial blood gas analyses. This study aimed to assess the outcomes of prehospital patients in relation to their prehospitally measured lactate, pH, and CO2 levels. The primary outcome was 7-day mortality.MethodsThis register-based cohort study included patients with one or more prehospital blood gas analyses during their prehospital treatment by a physician-manned MECU, from January 2015 to December 2018. The blood samples were analyzed on an ABL90 Flex analyzer. Absolute values with percentages and odds ratios (OR) with 95% confidence intervals (CI) were calculated for the primary and secondary outcomes within prespecified subgroups.ResultsThe study included 745 patients, with an overall 7-day mortality rate of 20.0%.Lactate levelThe 7-day mortality rates were 11.5% in patients with normal lactate levels (< 2.0 mmol/L), 14.4% with intermediate lactate levels (2.0–3.9 mmol/L), and 33.0% with high lactate levels (≥ 4.0 mmol/L). This corresponded to an OR of 1.30 (95% CI: 0.75–2.24) in the intermediate lactate group (2.0–3.9 mmol/L) and an OR of 3.77 (95% CI: 2.44–5.85) in the high lactate group (≥ 4.0 mmol/L), compared to the reference group with normal lactate.pH levelThe ORs of 7-day mortality rates were 4.82 (95% CI: 3.00–7.75) in patients with blood pH of < 7.35 and 1.33 (95% CI: 0.65–2.72) in patients with blood pH > 7.45, compared to the reference group with normal pH (7.35–7.45).CO2 levelThe ORs of 7-day mortality rates were 2.54 (95% CI: 1.45–4.46) in patients with blood CO2 of < 4.3 kPa and 2.62 (95% CI: 1.70–4.03) in patients with blood CO2 > 6.0 kPa, compared to the reference group with normal CO2 (4.3–6.0 kPa).ConclusionsThis study found a strong correlation between increasing 7-day mortality rates and high blood lactate levels, low levels of pH, and abnormal CO2 blood levels, in prehospital patients undergoing prehospital blood analysis.

Clinical case of lightning injury

Atmospheric electricity damage as a result of lightning strike is a relatively rare condition in intensive care medicine, however it can be accompanied by high mortality and serious complications in the majority of survived patients.The objective was to demonstrate a clinical case of lightning injury and discussion of diagnostic and treatment aspects in this condition.Materials and Methods. 18-yr old patient was delivered to hospital after lightning strike. She lost consciousness, there was no breathing for a short time, and the witnesses provided artificial respiration and external cardiac compressions. On admission, the signs of shock were present in parallel with dopamine infusion, the skin was pale-grey and cold, with traces of thermal damage according to the type of contact with metal of various localization on the neck, scalp, front surface of the chest and abdominal wall, in the groin, on the left foot. The patient was hospitalized to ICU, therapeutic and diagnostic measures were started. We revealed decompensated lactic acidosis, biochemical signs of myocardial and muscle damage. The infusion therapy, analgesics, antibiotics, proton pump inhibitors, anticoagulants were administered. During the therapy in the first 6 hours, the signs of shock were attenuated, in 4 days, the patient was transferred to traumatological department in a stable state. After the transfer from the ICU, hearing decline as well as pain and sensory disturbances in the left foot are persisting.Conclusion. An integrated approach is required in the diagnosis, treatment, and rehabilitation of patients with lightning injury.

Клиническое наблюдение синдрома Пирсона у ребенка 6 месяцев

Pearson syndrome (PS) is a rare mitochondrial disorder that typically manifests as transfusion-dependent macrocytic anemia, exocrine pancreatic dysfunction and lactic acidosis. Typical features of the bone marrow in PS are reduced cellularity, vacuolation of hematopoietic precursors and ringed sideroblasts. PS clinical manifestations may differ in neonatal age and develop as damage to various organs and systems. The PS incidence is unknown as yet with only about 100 patients described in scientific sources since the initial report. The Article presents a modern bibliographical review on PS and a description of a clinical case in a 6-month-old child that had manifested since birth as transfusion-dependent anemia, leukopenia and thrombocytopenia. Conclusion: examination of bone marrow puncture allows rapid assuming of a PS diagnosis in a patient.

The clinical spectrum of MELAS and associated disorders across ages: a retrospective cohort study.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a severe multisystemic disease, although some have a milder phenotype. We aimed to evaluate the clinical spectrum of this disease from MELAS patients to asymptomatic carriers and identify predictors of severity. We reviewed 81 patients, who had MELAS or had positive genetics without meeting clinical criteria. Patients who met criteria including lactic acidosis, encephalomyopathy, and stroke-like episodes (SLE) were categorized as MELAS, symptomatic non-MELAS, and asymptomatic. MELAS was further categorized as "standard-onset" if the first stroke-like episode (SLE) occurred before age 40 or "late-onset." Eighty-one patients were included: 42 MELAS (13 late-onset), 30 symptomatic non-MELAS, and 9 asymptomatic. MELAS patients had lower BMI at onset (mean 18.6 vs. 25.1 asymptomatic and 22.0 symptomatic non-MELAS, p < 0.05). There was a trend toward higher serum heteroplasmy in MELAS compared to symptomatic non-MELAS and asymptomatic (means 39.3, 29.3, and 21.8% p = 0.09). Symptomatic non-MELAS had more sensorineural hearing loss as first presenting symptom (51.6% vs. 24.4%, p < 0.05). MELAS had higher prevalence of seizures (88.1% vs. 16.7%, p < 0.05) and shorter survival from onset to death (50% mortality at 25 years vs. 10%, p < 0.05). Late-onset MELAS had longer disease duration from first symptom to first SLE (mean 16.6 vs. 9.3 yrs) and also lived longer (mean age at death 62 vs. 30). Standard-onset MELAS had more neurologic involvement at onset than late-onset (51.7% vs. 15.4%). Late-onset patients had more prevalent diabetes (69.2% vs. 13.8%) and nephropathy (53.8% vs. 10.3%). Patients with late-onset MELAS also had more organ systems involved (mean 4.1 vs. 2.7, p < 0.05). There was a trend toward higher heteroplasmy levels in standard-onset (mean 44.8% vs. 25.3%, p = 0.18). Our study highlights the spectrum of MELAS. The lower BMI in MELAS at presentation as well as higher rates of sensorineural hearing loss as initial symptom in symptomatic non-MELAS may be useful clinical markers. While many patients present before age 40 with SLE, some can present with SLE later in life. Standard onset MELAS is more likely to present with neurologic symptoms. Late-onset is more likely to suffer diabetes or nephropathy and have more organ systems involved.