Twin Premature Infants With Riboflavin and Biotin Deficiency Presenting With Refractory Lactic Acidosis, Rash, and Multiorgan Failure During Prolonged Parenteral Nutrition.

We are reporting monochorionic, diamniotic twin premature infants born at 25 weeks and 6 days gestation with riboflavin (vitamin B2) and biotin (vitamin B7) deficiency, while on prolonged total parenteral nutrition (TPN) during vitamin shortage. They presented initially with skin rash, lactic acidosis, and thrombocytopenia. Both twins progressed to severe respiratory failure, severe lactic acidosis, with refractory vasodilatory shock, pancytopenia, ischemic bowel injury, acute kidney injury, liver injury, and capillary leak syndrome leading to death of twin A. The surviving twin B was diagnosed with riboflavin and biotin deficiency that presented with abnormal metabolic work up suggestive of maple syrup urine disease, glutaric acidemia type 2, and X-linked adrenoleukodystrophy. Twin B was started on riboflavin and biotin supplementation at 41 days of life, with rapid improvement in clinical findings and laboratory abnormalities within days of starting biotin and riboflavin supplementation. He was discharged home in stable condition at 49 weeks of postmenstrual age.

Successful Treatment of Tenofovir Alafenamide-Induced Lactic Acidosis: A Case Report.

Nucleoside or nucleotide analogues (NAs) have the potential to cause lactic acidosis by inhibiting DNA polymerase-γ of human mitochondria and impairing aerobic metabolism. Patients may be asymptomatic, have mild non-specific symptoms, or present in multisystem organ failure. There is a paucity of data to guide management of life-threatening lactic acidosis due to NA therapy. Here we describe a case of a 60-year old critically ill male with decompensated cirrhosis secondary to hepatitis B virus (HBV) infection who developed severe lactic acidosis (13.8 mmol/L) 2 days after initiation of tenofovir alafenamide (TAF). All other possible etiologies for the elevated lactate were ruled out. Lactic acidosis resolved rapidly with TAF discontinuation and supplementation with cofactors supporting mitochondrial oxidative phosphorylation, including coenzyme Q10, levocarnitine, riboflavin, and thiamine. This case highlights the ability of TAF to cause lactic acidosis early after therapy initiation, especially in susceptible hosts, and reviews the potential role for cofactor supplementation for drug-induced mitochondrial injury.

Resistant Lactic Acidemia Due to Accidental Cheese Starter Culture Ingestion.

Lactic acid is the end-product of anaerobic glycolysis. It is generally believed that elevated blood lactate levels are associated with poor patient outcomes. Literature reports that lactic acidosis can be related to supplementary food intake in the pediatric age group however, in adult patients, it is not common to see lactic acidosis due to oral ingestion unless the patient has a history of short bowel syndrome or jejunoileal bypass surgery. With the current case presentation, we report an accidental cheese starter culture intake that resulted in resistant lactic acidosis with no signs of critical illnesses.

Cardiac Dysfunction Due to Thiamine Deficiency after Hemodialysis for Biguanide-related Lactic Acidosis.

Biguanide is an ideal drug for the treatment of type 2 diabetes mellitus. When used appropriately, the incidence of lactic acidosis is reported to be very low. Risk factors associated with biguanide-related lactic acidosis include chronic kidney disease, congestive heart failure, alcohol use, severe dehydration, shock, hypoxic states, sepsis, and advanced age. We herein report a case of cardiac dysfunction due to thiamine deficiency after hemodialysis in a patient with suspected biguanide-related lactic acidosis. Patients who develop severe lactic acidosis while taking biguanides should be given a large dose of thiamine without delay, given the possibility of thiamine deficiency as a complication.

Disturbance of consciousness due to hyperammonemia and lactic acidosis during mFOLFOX6 regimen: Case report.

INTRODUCTION: FOLFOX therapy is the main chemotherapy regimen for colorectal cancer. Peripheral neuropathy, hematotoxicity, and digestive symptoms are known to be the most frequent adverse events. Hyperammonemia and lactic acidosis rarely occur simultaneously during treatment with FOLFOX therapy; the number of case reports is limited worldwide. We report a case of disturbance of consciousness, considered to be caused by hyperammonemia and lactic acidosis that occurred during treatment with mFOLFOX6 therapy that was administered as postoperative adjuvant treatment for rectal cancer. PATIENT CONCERNS: This case was of a 71-year-old man who had been receiving oral treatment for chronic kidney disease and diabetes mellitus. Laparoscopic low anterior resection and artificial anal construction surgery were performed for stage III rectal cancer. As adjuvant postoperative therapy, mFOLFOX6 therapy was started but was followed by a disturbance of consciousness. DIAGNOSES: Results of the blood tests revealed notable hyperammonemia (ammonia level, 1,163 µg/dl) and lactic acidosis (pH 7.207; lactate, 17.56 mmol/L); however, imaging diagnosis did not reveal intracranial lesions that could cause disturbance of consciousness. INTERVENTIONS: For hyperammonemia, branched-chain amino acid agents and Ringers solution supplementation were administered. For acidosis, 7% sodium hydrogen carbonate was administered as treatment. OUTCOMES: The disturbance of consciousness improved within 12 hours of initiating the treatment, and the patient was discharged with no sequelae on 7th day after hospitalization. CONCLUSION: In patients with chronic kidney disease, FOLFOX regimen may confer risks of hyperammonemia and lactic acidosis.

The Dramatic Recovery of a Patient with Biguanide-associated Severe Lactic Acidosis Following Thiamine Supplementation.

Biguanides are a drug of choice for the treatment of type 2 diabetes mellitus. Although they can cause lactic acidosis in susceptible patients with predisposing risk factors, the incidence of lactic acidosis is reported to be very low when they are used properly. We herein present a case of biguanide-associated severe lactic acidosis complicated with thiamine deficiency that was provoked without predisposing factors for thiamine deficiency. Diabetic patients taking biguanide may be predisposed to thiamine deficiency, even when there is no evidence of risk factors, and the high-dose administration of thiamine may be essential in the treatment of this otherwise under-recognized disorder.

Lactic acidosis following intentional overdose by inhalation of salmeterol and fluticasone.

Salmeterol, a long-acting ß2-adrenergic receptor agonist used for the treatment of asthma and chronic obstructive pulmonary disease, has an adverse effects profile that is similar to that of salbutamol and other ß2-agonists. We report a sympathomimetic syndrome with metabolic acidosis and hyperlactatemia after intentional inhalation of salmeterol in a suicide attempt. A 16-year-old female patient was admitted to the emergency department approximately 2 hours after having inhaled 60 puffs of a combination of salmeterol xinafoate 25 µg and fluticasone propionate 50 µg. She presented in an anxious state with complaints of palpitations and chest pain. The electrocardiogram demonstrated sinus tachycardia and ST-segment depression in the inferior and anterolateral leads. Laboratory findings showed hypokalemia, hypophosphatemia, and lactic acidosis. Cardiac troponin I and creatine kinase MB remained within the normal range. Treatment was supportive and included intravenous fluids and cautious potassium supplementation. The next day, electrocardiographic and laboratory findings returned to normal. We hypothesize that stimulation of ß2-adrenergic receptors by inhalation of salmeterol caused this patient's lactic acidosis. This observation is consistent with the hypothesis that the hyperlactatemia observed during asthma attacks is due in part to the administration of high doses of ß2-agonists. Salmeterol overdose by inhalation appears to be sufficient to cause lactic acidosis.

Adulteration of herbal antidiabetic products with undeclared pharmaceuticals: a case series in Hong Kong.

AIMS: The current study aims to examine the problem of adulteration of herbal antidiabetic products with undeclared pharmaceuticals, including both registered and banned drugs. METHODS: All cases involving use of adulterated herbal antidiabetic products referred to a tertiary centre for clinical toxicology analysis from 2005 to 2010 inclusive were retrospectively reviewed. The patients' demographic characteristics, clinical presentations, medical history, drug history and the analytical findings of the herbal antidiabetic products were studied. RESULTS: A total of 27 cases involving use of 29 adulterated herbal antidiabetic products were identified. Seventeen of the patients (63%) had clinical toxicities associated with the illicit products. Hypoglycaemia was the most common adverse effect, followed by lactic acidosis. Analysis of the 29 illicit herbal antidiabetic products revealed eight undeclared registered or banned oral antidiabetic agents, namely glibenclamide (n= 22), phenformin (n= 18), metformin (n= 6), rosiglitazone (n= 6), gliclazide (n= 2), glimepiride (n= 2), nateglinide (n= 1) and repaglinide (n= 1). Non-antidiabetic drugs were also detected in some products. Up to four adulterants were detected within the same product. CONCLUSIONS: Adulteration of herbal antidiabetic products with undeclared pharmaceuticals is a significant yet under-recognized problem. Patients taking these illicit products could be at risk of potentially fatal adverse effects. It is important to educate the public to avoid taking pCMs of dubious source. Effective regulatory measures should be put in place to address the problem.

Severe metabolic acidosis secondary to coadministration of creatine and metformin, a case report.

It is known from studies in young athletes that creatine supplements have beneficial effects on muscular functional capacity, so it is being widely used as a performance-enhancing substance in both professional and amateur sports men and women. They are approved and considered relatively safe, but there have been a few case reports of renal dysfunction associated with their use. We present the case of a patient who developed acute renal failure and lactic acidosis while using creatine and metformin simultaneously.

A case of Kombucha tea toxicity.

INTRODUCTION: Kombucha "mushroom'' tea is touted to have medicinal properties. Here, we present a case of hyperthermia, lactic acidosis, and acute renal failure within 15 hours of Kombucha tea ingestion. CASE PRESENTATION: A 22 year old male, newly diagnosed with HIV, became short of breath and febrile to 103.0F, within twelve hours of Kombucha tea ingestion. He subsequently became combative and confused, requiring sedation and intubation for airway control. Laboratories revealed a lactate of 12.9 mmol/L, and serum creatinine of 2.1 mg/dL. DISCUSSION: Kombucha tea is black tea fermented in a yeast-bacteria medium. Several case reports exist of serious, and sometimes fatal, hepatic dysfunction and lactic acidosis within close proximity to ingestion. CONCLUSION: While Kombucha tea is considered a healthy elixir, the limited evidence currently available raises considerable concern that it may pose serious health risks. Consumption of this tea should be discouraged, as it may be associated with life-threatening lactic acidosis.

Hazards posed by a banned drug--phenformin is still hanging around.

The Hospital Authority Toxicology Reference Laboratory confirmed six cases of phenformin use, with or without complications, from July 2005 to November 2006. Two of the patients presented with potentially fatal phenformin-induced lactic acidosis. Phenformin was found (or suspected to be) adulterating Chinese proprietary medicine in five of the six cases. We report these six cases to highlight the underrecognised hazards posed by phenformin, a banned drug in Hong Kong.

Glucose loading precipitates focal lactic acidosis in the vulnerable medial thalamus of thiamine-deficient rats.

Glucose loading in thiamine-deficient patients is known to precipitate Wernicke's Encephalopathy; however, the mechanisms responsible have not been fully elucidated. Lactate accumulation occurs in brains of thiamine-deficient rats. In order to determine whether glucose loading in thiamine-deficient rats causes selective lactic acidosis in vulnerable brain structures, cerebral pH was measured autoradiographically using 14-labeled 5,5-dimethyloxazolidine-2, 4-dione ([(14)C]DMO) in the medial thalamus, a vulnerable brain region, versus cerebral cortex, a brain region that is spared in thiamine deficiency. Following administration of a glucose load, regional lactate levels and de novo lactate synthesis measured by (1)H-(13)C-NMR spectroscopy, increased significantly to 21.86 +/- 3.04 mumol/g (wet weight) in the medial thalamus (p < 0.001) and pH in this brain region was decreased significantly from 7.08 +/- 0.04 to 6.87 +/- 0.05 (p < 0.001). No such changes were observed in cerebral cortex following a glucose load. These results demonstrate that the increased production and accumulation of brain lactate result in acidosis following glucose loading in thiamine deficiency. Alterations of brain pH could contribute to the pathogenesis of thalamic neuronal damage and consequent cerebral dysfunction in Wernicke's Encephalopathy.

[Lactic acidosis and accumulation of glutamate in the blood of neonates following treatment with calcium levulinate for hypocalcaemia]. / Lactaatacidose en glutamaatophoping in het bloed van neonaten na behandeling met calciumlevulaat wegens hypocalciëmie.

The data from 5 clinics concerning 8 infants, who had developed severe lactic acidosis and hyperglutamic acidaemia were reviewed. Blood-lactate levels were up to 15 mmol/l (reference level: < 2) and plasma-glutamate levels up to 1632 pmol/l (reference level: 14-78), and there was no concomitant hyperglutaminaemia (levels up to 1032 micromol/l (reference level: 333-809)). A positive correlation between the amount of calcium levulinate administered and the degree of hyperglutamic acidaemia was found. Replacement of the calcium levulinate by another calcium salt caused a reversal of the biochemical abnormalities of the patients. Two of the infants had a 22q11 microdeletion. This development of severe acidosis in infants who had been given a calcium supplement in the form of calcium levulinate may be related to genetic predisposition. The paradoxal hyperketonaemia and generalized aminoaciduria in 4 other patients suggested disturbed function ofthe mitochondrial respiratory chain. The hypothesis of the occurrence of an underlying defect of the mitochondrial respiratory chain was tested in the muscle tissue of one 22q11 patient, but this showed no abnormalities. Excessive accumulation of glutamate because of dysfunction ofglutamine synthetase, which forms glutamate from glutamine seems unlikely because of the relatively low values of plasma glutamate compared to the glutamine plasma levels. Calcium levulinate should no longer be used in neonates as it may lead to lactic acidosis.

Lactic acidosis in an HIV-infected patient receiving highly active antiretroviral therapy.

BACKGROUND: A 51-year-old man with HIV infection on highly active antiretroviral therapy presented with abdominal pain and exertional dyspnea. Physical examination revealed increased respiration and cachexia. Laboratory tests showed a lactic acid concentration elevated to 6.4 mM. INVESTIGATION: Physical examination, blood chemistry, arterial blood gas, urine analysis, chest X-ray, and ultrasound of liver. DIAGNOSIS: Nucleoside reverse transcriptase inhibitor (NRTI)-induced lactic acidosis, hepatitis and chemical pancreatitis. Proximal renal tubular acidosis with Fanconi's syndrome, secondary to treatment with tenofovir. MANAGEMENT: The patient was supported on intravenous and oral bicarbonate, riboflavin and phosphorus supplementation. Highly active antiretroviral therapy was discontinued. The patient's lactate level decreased about 2 weeks after discharge.

Buformin suppresses the expression of glyceraldehyde 3-phosphate dehydrogenase.

The biguanides metformin and buformin, which are clinically used for diabetes mellitus, are known to improve resistance to insulin in patients. Biguanides were reported to cause lactic acidosis as a side effect. Since the mechanism of the side effect still remains obscure, we have examined genes whose expression changes by treating HepG2 cells with buformin in order to elucidate the mechanisms of the side effect. A subtraction cDNA library was constructed by the method of suppressive subtractive hybridization and the screening of the library was performed with cDNA probes prepared from HepG2 cells treated with or without buformin for 12 h. The expression of the gene and the protein obtained by the screening was monitored by real-time RT-PCR with specific primers and Western blotting with specific antibody. The amounts of ATP and NAD+ were determined with luciferase and alcohol dehydrogenase, respectively. We found that expression of the glyceraldehyde 3-phosphate dehydrogenase (GAPD) gene was suppressed by treating HepG2 cells with 0.25 mM buformin for 12 h as a result of the library screening. The decrease in the expression depended on the treatment period. The amount of GAPD protein also decreased simultaneously with the suppression of the gene expression by the treatment with buformin. The amount of ATP and NAD+ in the HepG2 cells treated with buformin decreased to 10 and 20% of the control, respectively. These observations imply that the biguanide causes deactivation of the glycolytic pathway and subsequently the accumulation of pyruvate and NADH and a decrease in NAD+. Therefore, the reaction equilibrium catalyzed by lactate dehydrogenase leans towards lactate production and this may result in lactic acidosis.

[Lactic acidosis in HIV-patients--diagnosis and treatment]. / Laktatazidose bei HIV-Patienten erkennen und behandeln. Hier ist rasches Handeln angesagt.

Lactic acidosis is a life-threatening complication of antiretroviral therapy with an incidence of about 1% per year. Its clinical onset is often abrupt, with uncharacteristic muscular, cardiac or hepatic symptoms. Lactic acidosis is caused by nucleoside analogue reverse transcriptase inhibitors (mainly didanosine, stavudine and zalcitabine), which are relatively strong inhibitors of gamma polymerase, the enzyme responsible for the replication of mitochondrial DNA. Zidovudine is also a mitochondrial toxin, but its toxicity probably reflects several mechanisms unrelated to mtDNA-depletion. When lactic acidosis is diagnosed, nucleoside analogues and other mitochondrial toxins, such as valproic acid and acetylsalicylic acid, must be discontinued immediately. Uridine should be supplemented, a cocktail consisting of vitamins, L-carnitine and coenzyme Q10, may be given.

Acidosis láctica y terapia anti-VIH: una asociación infrecuente / Lactic acidosis and human immunodeficiency virus therapy: an infrequent association

La toxicidad mitocondrial es un efecto adverso poco frecuente del tratamiento con algunos antirretrovirales que, entre otros síntomas, se manifiesta por acidosis láctica. Describimos el caso de una paciente con infección por el virus de la inmunodeficiencia humana (VIH) que había recibido tratamiento con antirretrovirales del tipo inhibidores de la transcriptasa inversa e inhibidores de la proteasa durante un año y que ingresó en la unidad de cuidados intensivos (UCI) por un cuadro de shock e insuficiencia renal aguda oligúrica. En los diferentes estudios realizados, destacaba una acidosis láctica grave. A pesar de la retirada del tratamiento con antirretrovirales la paciente evolucionó hacia el fracaso multiorgánico (respiratorio, hemodinámico, renal y hematológico), y falleció a las 20 horas del ingreso (AU)