Unexplained Metabolic Acidosis Research Articles

TOXIC ALCOHOL POISONING: A CASE REPORT

During the COVID-19 pandemic, toxic alcohol poisoning, notably from methanol, has emerged as a significant concern due to increased consumption of illicit liquor amidst lockdown restrictions. We present a case of a middle-aged man who developed altered consciousness, metabolic acidosis, and shock two days after ingesting hospital spirit. Although initial qualitative tests only detected ethanol, subsequent MRI findings showed classical signs of methanol poisoning, including basal ganglia abnormalities. Prompt management with dialysis, ventilatory support, and adjunctive therapy successfully addressed the acute phase despite the patient remaining delirious for seven days. This case underscores the importance of considering methanol toxicity even in the absence of direct evidence, necessitating comprehensive diagnostic approaches. Awareness and incorporating point-of-care assessments such as arterial blood gas analysis and osmolar gap evaluation in suspected cases are crucial, especially in resource-limited settings. Recognizing unexplained high anion gap metabolic acidosis with a high osmolar gap and characteristic MRI findings can aid in the early diagnosis and management of toxic alcohol poisoning

Starvation Ketoacidosis on the Acute Medical Take: An Easily Missed Complication of the Keto Diet.

Always check ketones in patients with an unexplained metabolic acidosis; there can be overlap between starvation, alcohol-related and lactic acidosis.Management of starvation ketoacidosis is often empirical, involving close monitoring of fluid status and electrolytes.Clinicians should discuss the risk of ketoacidosis associated with the ketogenic diet in women who plan to breast-feed and lose weight following pregnancy.

Dihydrolipoamide dehydrogenase deficiency in five siblings with variable phenotypes, including fulminant fatal liver failure despite good engraftment of transplanted liver.

Dihydrolipoamide dehydrogenase (DLD) deficiency can, in one of its forms, be a rare cause of acute liver failure. Clinical presentation is nonspecific. Biochemical findings can reflect metabolic block, but vary depending on patient and his condition. Consensus treatment guidelines do not exist. We present a family with five members suffering from DLD deficiency. Patient 1 presented with emesis, mental deterioration, and fulminant hepatic failure, which required high-urgency liver transplantation. His younger brother, patient 2, experienced unexplained hypoglycemia and metabolic acidosis on the second day after cardiac surgery. Three affected younger siblings were asymptomatic. In patients with acute liver failure of unknown etiology urgent metabolic work-up should be done, and whole exome sequencing considered. Liver transplantation remains life-saving treatment option, but its outcome may be dependent on etiology-specific supportive treatment.

Clinical manifestations and renal pathology of ethylene glycol.

Ethylene glycol (EG) poisoning is a critical medical emergency often associated with suicide attempts in adults. EG is metabolized by alcohol dehydrogenase, leading to the formation of toxic metabolites that cause metabolic acidosis, renal failure, hypocalcemia, aciduria, and disorders of the central nervous and cardiovascular systems. Calcium oxalate, a metabolite of EG, contributes to acute tubular necrosis. Despite limited reports on human renal pathology, we present a case detailing renal pathology following EG ingestion. A 44-year-old male, admitted due to loss of consciousness, had ingested a lethal dose of EG. Blood tests indicated metabolic acidosis, while urinary examination revealed calcium oxalate crystals. Continuous renal replacement therapy corrected the acidosis; however, nephrogenic diabetes insipidus subsequently developed. A renal biopsy on day 31 revealed calcium oxalate crystal deposition and tubulointerstitial damage. Notably, various stages of crystal deposition, adherence, and degradation were observed. This case underscores the importance of considering EG poisoning in cases of unexplained metabolic acidosis and renal dysfunction, with renal biopsy serving as a valuable diagnostic tool. Understanding the renal effects of EG is essential for timely intervention and effective management of poisoning cases.

Factors associated with D-lactic acidosis in pediatric intestinal failure: A case-control study.

D-lactic acidosis (DLA) is a serious complication of short bowel syndrome (SBS) in children with intestinal failure (IF). Malabsorbed carbohydrates are metabolized by bacteria in the intestine to D-lactate which can lead to metabolic acidosis and neurologic symptoms. A retrospective chart review was performed in children ≤18 years old with SBS who had one of the following criteria: unexplained metabolic acidosis, neurologic signs or symptoms, history of antibiotic therapy for small bowel bacterial overgrowth, or high clinical suspicion of DLA. Cases had serum D-lactate concentration >0.25 mmol/L; controls with concentrations ≤0.25 mmol/L. Of forty-six children, median age was 3.16 (interquartile range (IQR): 1.98, 5.82) years, and median residual bowel length was 40 (IQR: 25, 59) cm. There were 23 cases and 23 controls. Univariate analysis showed that cases had significantly lower median bicarbonate (19 vs. 24 mEq/L, p = 0.001), higher anion gap (17 vs. 14 mEq/L, p < 0.001) and were less likely to be receiving parenteral nutrition, compared with children without DLA. Multivariable analysis identified midgut volvulus, history of intestinal lengthening procedure, and anion gap as significant independent risk factors. Midgut volvulus was the strongest independent factor associated with DLA (adjusted odds ratio = 17.1, 95% CI: 2.21, 133, p = 0.007). DLA is an important complication of pediatric IF due to SBS. Patients with IF, particularly those with history of midgut volvulus, having undergone intestinal lengthening, or with anion gap acidosis, should be closely monitored for DLA.

Assessing the Role of Initial Serum Calcium Concentration in Patients with Ethylene Glycol Poisoning.

Assays for ethylene glycol (EG) with a rapid turn-around time are not routinely available. Clinicians must rely on historical features and readily available clinical tests, combined with clinical acumen, to guide the initial management of suspected EG poisoning. Hypocalcemia has been suggested as a clue supporting the diagnosis of EG poisoning in patients presenting with an unexplained high anion gap metabolic acidosis (HAGMA). A previous small study challenged this assumption. This was a retrospective case series of one state's poison control system of confirmed EG-poisoned patients between September 2017 and April 2021. The definition of EG poisoning was based on suspected EG ingestion and a serum EG concentration > 5 mg/dL. Patients who were suspected to have EG toxicity but did not have a confirmed EG concentration or the EG concentration was less than 5 mg/dL were excluded. Routine laboratory studies were recorded for all patients. Comparisons between serum calcium on presentation to presenting blood pH, bicarbonate, anion gap, and creatinine were assessed for correlation. There was no correlation between the presenting calcium and either pH or creatinine. There was a weak positive correlation between the initial serum calcium and anion gap, a weak negative correlation between the initial serum calcium and bicarbonate. On hospital presentation, hypocalcemia was not associated with EG poisoning, even in patients with a HAGMA. A normal serum calcium on presentation does not exclude the diagnosis of EG poisoning.

SGLT2-Inhibitors and Euglycemia Diabetic Ketoacidosis: A Missed Diagnosis

Euglycemic diabetic ketoacidosis (EuDKA), is an uncommon but potentially fatal medical emergency characterized by metabolic acidosis, ketosis, and either normal or near normal blood glucose level. The Diagnosis is delayed due to a lack of hyperglycemia leading to adverse consequences. It’s not a routine diagnosis but patients with both types of diabetes mellitus may suffer from it. Since august 2014, after the inclusion of sodium-glucose cotransporter-2 inhibitors (SGLT2i) for the management of diabetes mellitus, the incidence of euglycemia DKA has raised. The other conditions that may contribute to this metabolic disorder include fasting, chronic liver disease, pregnancy, gastroparesis, bariatric surgery, glycogen storage disease, cocaine intoxication, and insulin pump failure. Euglycemic DKA, a diagnosis of exclusion, should be considered in any unexplained metabolic acidosis among diabetic patients, who report to the hospital with nonspecific symptoms not suggesting DKA and have been taking sodium-glucose cotransporter-2 inhibitors. Here we are describing a case of ketoacidosis with normoglycemia caused by empagliflozin in a female suffering from type 2 diabetes mellitus to raise awareness of physicians to minimize the delays in the identification of this life-threatening metabolic disorder.

294 BEYOND BRUGADA SYNDROME: A COMMON ECG PATTERN IN AN UNCOMMON CLINICAL SCENARIO

Abstract Propofol infusion syndrome (PRIS) is a rare but potentially lethal side effect of propofol. In most cases it shows various combinations of signs such as unexplained metabolic acidosis, rhabdomyolysis, hepatomegaly, renal failure, hypertriglyceridemia, malignant arrhythmia and rapidly progressive cardiac failure. The development of coved ST elevation in the right precordial leads of the electrocardiogram (ECG), similar to that seen in the type I Brugada syndrome may be the first sign of cardiac instability. There is no specific treatment for PRIS. Successful management consists of an early recognition of its signs followed by a prompt propofol infusion termination. We present the case of a 35-year-old male affected by mild hypertension. He was found by his wife during a transitory loss of consciousness episode. He had resulted positive to Sars Cov 2 infection a day before and was symptomatic for fever and myalgia. An ambulance was immediately called and the patient was transferred to the emergency department for a suspected out-of-hospital-cardiac arrest. The initial one-lead ECG performed by the emergency physician was unremarkable. On arrival he was in a coma state but with stable hemodynamics. ECG showed only an asymmetric T wave inversion in V4-V6 leads. The cardiac echocardiogram did not show any major alterations. In the meantime, due to worsening of respiratory function, orotracheal intubation was performed and the patient was sedated with propofol, midazolam and fentanyl. Subsequently, an episode of atrial fibrillation was documented. Amiodarone infusion was started and the patient reverted to sinus rhythm after a few hours. The following day two episodes of Torsade de Pointes during prolonged QTc (660 ms) occurred. These arrhythmias were treated successfully with magnesium sulfate infusion. Blood analysis showed severe hypokalemia that was immediately corrected. After the hemodynamic stabilization the ECG showed a pattern highly resembling the Brugada pattern type 1 in the right precordial leads. Moreover CPK, myoglobin, high sensitivity troponin I levels started to rise, along with creatinine, triglycerides and markers of hepatic injury. Propofol had been administered continuously for eight days, so PRIS was suspected as the primum movens of this clinical scenario. Propofol infusion was immediately interrupted. Thereafter, the patient gradually improved and was extubated. As soon as the patient's hemodynamic conditions allowed it, a coronary CT and a cardiac MRI were performed, but were unremarkable. To further evaluate the case, a flecainide challenge test was performed, but no significant ECG change was induced. Nonetheless, given both the history of ventricular arrhythmia, the young age of the patient and the unexplained transitory loss of consciousness a subcutaneous defibrillator was implanted as a form of secondary prevention.

ODP043 Hypokalemia in Autoimmune Polyglandular Syndrome: A Case of Newfound Type I (Distal) Renal Tubular Acidosis

Abstract Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy Type 1 (APECED) is a rare autosomal recessive disorder predisposing to early development of chronic mucosal candidiasis and progressive development of various endocrinopathies, such as Addison's disease, Primary Hypoparathyroidism, and Type 1 Diabetes (T1D). Few cases described in literature regarding renal involvement in this disorder, with most common manifestation being tubulo-interstitial nephritis, however, there is limited evidence regarding presentation of APECED with hypokalemia due to concomitant Type I Renal Tubular Acidosis (RTA). Case of a 47-year-old female with past medical history of APECED Type 1 (consisting of hypoparathyroidism, adrenal insufficiency, and chronic mucocutaneos candidiasis), T1DM on honeymoon, hypothyroidism, and nephrolithiasis presenting to the emergency department complaining of bilateral upper and lower extremity weakness of one week in evolution, but worsening on day of admission. Denies associated constitutional symptoms. Strong positive first-degree relative history for autoimmune diseases. Physical examination: 2/5 strength in all four extremities, deep tendon reflexes grossly intact, no gross sensory or motor deficits. Patient on oral steroid therapy for her Addison's, calcitriol supplementation for hypoparathyroidism, and potassium chloride supplementation since a prior hypokalemic episode 17 years ago. Laboratory workup results remarkable for sodium: 140 mmol/L (N: 135-144 mmol/L), chloride: 110 mmol/L (N: 95-105 mmol/L), potassium: 2. 0 mmol/L (N: 3.4-4.5 mmol/L), central bicarbonate: 18mmol/L (N: 23-31 mmol / L), anion gap: 12 (N: 10-12), glycosylated hemoglobin: 5.2% (N: 4.7-6.2%) and anti-glutamic acid decarboxylase antibodies &amp;gt;25,000 U/mL (N: &amp;lt;5 U/mL). Adrenal insufficiency was ruled out by laboratory findings, but she had normal anion gap metabolic acidosis (NAGMA) and hypokalemia. Urinalysis was negative for urinary tract infection but with pH: 7. 0 (N: 4.5-8. 0). Urine spots, measured to find the cause of her NAGMA, showed urine sodium: 92 mmol/L, urine potassium: 10 mmol/L, urine chloride: 90 mmol/L, and urine anion gap of 12 mEq/L, which is positive and suggests low urinary NH4+, consistent with Type I (Distal) RTA as the main etiology. Patient started on IV potassium replacement, which increased potassium to 3.8 mmol/L, and improved acidotic state, with central bicarbonate of 29mmol/L, and overall symptoms. Patient was discharged home with alkali therapy (Sodium citrate) for Type I (Distal) RTA. RTA is an underrecognized condition that may be inherited or acquired. Diagnosis is difficult but can be verified with a thoughtful workup. RTA should be considered for any patient with otherwise unexplained hyperchloremic metabolic acidosis and may be the presenting manifestation of autoimmune diseases. Regular renal monitoring for any APECED patient should be performed. We present this case as evidence for the coexistence of several different immune-mediated diseases in the clinical context of APECED with an unusual concomitant Type I (Distal) RTA, where there is few documented evidence of association with this disorder. Presentation: No date and time listed

A novel TCN2 mutation with unusual clinical manifestations of hemolytic crisis and unexplained metabolic acidosis: expanding the genotype and phenotype of transcobalamin II deficiency

BackgroundTranscobalamin deficiency is a rare inborn metabolic disorder, characterized by pancytopenia, megaloblastic anemia, failure to thrive, diarrhea, and psychomotor retardation.Case presentationWe describe a patient who first presented at 3 months of age, with pancytopenia, hepatosplenomegaly, recurrent infection, metabolic acidosis, and acute hemolytic crisis. Extensive hematologic and immunologic investigations did not identify inherited bone marrow failure syndrome, acute leukemia or its related disorders. Whole exome sequencing identified a novel homozygous TCN2 mutation, c.428-2A > G and mRNA study confirmed an aberrant transcription of exon 4 skipping. The mutant protein is predicted to have an in-fame 51 amino acids deletion (NP_000346:p.Gly143_Val193del). The patient exhibited marked clinical improvement following hydroxocobalamin treatment.ConclusionsTranscobalamin deficiency should be investigated in infants with unexplained pancytopenia and acute hemolytic crisis with or without typical evidence of vitamin B12 deficiency.

Methanol Intoxication After Suicidal Ingestion of Liquid Rodenticides: A Report of Two Cases.

Methanol is highly toxic to humans. Although methanol poisoning is not uncommon in developing countries, poisoning caused by ingestion of commercial products containing undeclared methanol has rarely been reported. Herein, we describe two patients who experienced methanol poisoning after ingestion of liquid rodenticides. A 39-year-old woman attempted suicide by ingesting liquid rodenticide which contained bromadiolone. She developed high anion gap metabolic acidosis and coagulopathy. Methanol poisoning was confirmed 20 hours later. She received oral ethanol therapy and hemodialysis. Vitamin K1 was also administered. She did not develop any hemorrhage or visual impairment and was discharged after 11 days. The rodenticide sample was tested and found to have a methanol concentration of 324 g/L. In another case, a 62-year-old man ingested the same brand of rodenticide. Laboratory data showed mild metabolic acidosis with an increased osmol gap, suggestive of methanol poisoning. He received hemodialysis and eventually recovered without sequelae. Liquid rodenticide may contain methanol as a solvent. Ingestion of a methanol-containing commercial product without a clear label can result in a considerable delay in diagnosis and management. Methanol poisoning should be considered for patients who present with unexplained metabolic acidosis following exposure to liquid rodenticides or other liquid commercial products.

An unusual cause of acute encephalopathy: D-lactic acidosis secondary to short bowel syndrome

Background: Blood D-lactate levels increase in short bowel syndrome (SBS) and may lead to neurological manifestations. Clinical Description: A 5-year-old boy, postoperative case of SBS, presented with loose stools, generalized weakness, and lethargy for 2 days. The child had undergone significant intestinal resection in the past. On examination, he had some dehydration, and was drowsy, but arousable. Remaining examination was normal. Metabolic abnormalities detected included metabolic acidosis (pH of 7.1, HCO3 7 mmol/L), high anion gap (20 mmol/l), and normal lactate levels (2 mmol/L). Other baseline investigations were normal. He was treated as a case of acute gastroenteritis with some dehydration and metabolic acidosis and improved. He was discharged after 5 days. After 2 months, he was readmitted with drowsiness and unsteady gait. This time there was no diarrhea or dehydration. Investigations again revealed severe metabolic acidosis, high anion gap, and normal lactate levels. Management: We considered SBS induced D-lactate encephalopathy but were unable to prove it by assay due to unavailability of tests. The child was kept nil per orally and given bicarbonate infusion, on which he showed dramatic improvement. He was also given a low carbohydrate diet and oral metronidazole. The family was counseled at discharge 5 days later regarding dietary modifications and microsupplementation. The patient had 6 admissions for D-lactic encephalopathy over 4 years that coincided with dietary lapse. Conclusion: D-lactate acidosis is an underrecognized condition and its diagnosis and management is challenging. A high index of suspicion should be kept in patients with history of intestinal resection presenting with acute encephalopathy and unexplained metabolic acidosis.

A case report of a first pregnant woman with late-onset multiple acyl-CoA dehydrogenase deficiency in Saudi Arabia

Background: Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric aciduria II, is a rare autosomal recessively inherited disorder of inborn error of metabolism. It can mainly be presented in three phenotypes: severe neonatal onset with a dysmorphic feature, neonatal-onset without dysmorphic features, and less severe mild late-onset phenotype. Case presentation: A 34-year-old Saudi female previously healthy, Para 4, with severe metabolic acidosis, rhabdomyolysis intrapartum was presented to us. Her previous pregnancy history and deliveries were unremarkable; she has three healthy sons. Since the beginning of this pregnancy, she complained of fatigability and muscle weakness which was progressive with time. At 36 weeks of gestation, she was presented to the emergency room with labor pain. She deteriorated rapidly with significant drowsiness. Her arterial blood gas showed severe metabolic acidosis with a high anion gap and normal lactate. She was intubated and underwent emergency cesarean delivery under general anesthesia. After the operation, she was sent to the intensive care unit. She passed away after a few days. A molecular test confirmed the diagnosis of MADD. Conclusion: First, late-onset MADD is a rare, underdiagnosed disease in adults. Second, the biochemical diagnosis of late-onset MADD is challenging as it mimics medium chain acyl CoA dehydrogenase deficiency which makes the molecular diagnosis essential for diagnosis. Third, for any unexplained myopathy, cardiac dysfunction, encephalopathy, or metabolic acidosis, metabolic disorders must be considered as early consultation with metabolic service.

Metabole acidose met verhoogde anion gap ten gevolge van 5-oxoprolinurie bij gelijktijdig gebruik van acetaminofen en flucloxacilline

Metabolic acidosis with increased anion gap due to 5-oxoprolinuria with concomitant use of acetaminophen and flucloxacillin 5-oxoprolinuria is a relatively rare metabolic disorder in which there is accumulation of 5-oxoproline leading to a high anion gap metabolic acidosis. The acquired form is usually caused by simultaneous use of acetaminophen (also known as paracetamol) and flucloxacillin, which is not uncommon. The exact incidence and prevalence of the acquired form are not known. This disorder is most likely under-reported as the test used for diagnosis is not always performed nor easy accessible. Diagnosing 5-oxoprolinuria requires testing urine or serum of a patient for the presence of organic acids, which are highly elevated in 5-oxoprolinuria. Due to the relative rareness of the disorder, cases are easily missed. 5-oxoprolinuria should always be suspected in a patient with unexplained high anion gap metabolic acidosis and/or therapy with flucloxacillin with or without the concomitant use of acetaminophen. Treating 5-oxoprolinuria is straightforward and consists of stopping the offending drug(s) which mostly leads to a spontaneous recovery. Treatment with sodium bicarbonate and/or N-acetylcysteine are also described in the literature, but at present there is not sufficient evidence supporting their use.

Role of Immune System against Sepsis

Sepsis, which is a highly heterogeneous syndrome, can result in death as a consequence of a systemic inflammatory response syndrome. The activation and regulation of the immune system play a key role in the initiation, development and prognosis of sepsis.[1]The roles of inflammation and coagulation in the pathophysiology of sepsis are described. Sepsis results when an infectious insult triggers a localized inflammatory reaction that then spills over to cause systemic symptoms of fever or hypothermia, tachycardia, tachypnea, and either leukocytosis or leukopenia. These clinical symptoms are called the systemic inflammatory response syndrome. Severe sepsis is defined by dysfunction of one of the major organ systems or unexplained metabolic acidosis. The inflammatory reaction is mediated by the release of cytokines, including tumor necrosis factor-alpha, interleukins, and prostaglandins, from neutrophils and macrophages. The cytokines activate the extrinsic coagulation cascade and inhibit fibrinolysis. Monocyte-macrophage cells and dendritic cells play a key role in the innate immune response. These cells have the ability to phagocytosis bacteria and interact with their products through an interaction with their pattern-recognition receptors.[13]These overlapping processes result in microvascular thrombosis; thrombosis is one potential factor producing organ dysfunction. Activation of the coagulation system leads to consumption of endogenous anticoagulants (e.g., protein C and Anti-thrombin); this may be an important factor in the development of microvascular coagulation. Anti-inflammatory mediators as well as inflammatory mediators have a role in sepsis, and an excess of either can result in poor patient outcomes. Sepsis is a complex syndrome involving activation of a variety of systems.[2]In this article, we try to further investigateThe role of the Human Immune System against various infections mostly Blood infection (Sepsis).

Unexplained life-threatening high anion gap metabolic acidosis: the answer is in the urine!

Unexplained life-threatening high anion gap metabolic acidosis: the answer is in the urine!

Euglycemic diabetic ketoacidosis associated with SGLT2i use: Case series.

Euglycemic diabetic ketoacidosis (EuDKA) associated with Sodium-Glucose Cotransporter-2 inhibitor (SGLT2i) use has been described but remains poorly understood. Data on Emergency Department (ED) presentation, resource utilization, and safety outcomes for these patients are lacking. We report a case series of patients diagnosed with EuDKA in the ED. An electronic medical record search identified adult patients presenting to a large tertiary ED with EuDKA. They were screened for concurrent use of SGLT2i. Clinical presentation, resource utilization, safety, and disposition data were collected and described. Five patients were included for analysis. Median age [range] was 57 [43-73] years. Presenting symptoms included nausea, vomiting, fatigue, and altered mental status. Initial results included: serum glucose 191mg/dL [176-215], venous pH7.01 [6.95-7.30], serum HCO3 8mEq/L [6-13], anion gap 27 [26-31], serum beta-hydroxybutyrate 9.9mmol/L [9.2-12.3], and urine ketones 150 [150-150]. Patients remained on an insulin infusion for 18.77h [11.25-56.48]. There were zero episodes of hypoglycemia and one episode of hypokalemia while on insulin infusion. Time to resolution of metabolic acidosis was 23.82h [15.45-24.77]. We report a case series of ED patients with EuDKA associated with SGLT2i use, and describe presentation characteristics, resource utilization, and safety outcomes. Emergency physicians should be aware of the association between SGLT2i use and EuDKA. An appropriate work-up should be pursued for patients taking an SGLT2i who present with symptoms suggestive of DKA, including nausea, vomiting, malaise, and altered mental status, or are noted to have an unexplained elevated anion gap metabolic acidosis.

Pseudo-anion gap metabolic acidosis from severe hypertriglyceridemia corrected by plasma exchange .

Falsely low or even unmeasurable serum bicarbonate has been described in patients with severe hypertriglyceridemia or paraproteinemia. This phenomenon, known as pseudo-hypobicarbonatemia, is believed to be due to interference by these components when the commonly used enzymatic assay is utilized for serum bicarbonate measurement. The calculated bicarbonate derived from blood gas machines is not affected. This can lead to a misdiagnosis of a severe anion gap metabolic acidosis along with an extensive and expensive work-up. We review a series of 5 patients with severe hypertriglyceridemia who presented with pseudo-hypobicarbonatemia and an elevated anion gap metabolic acidosis. Membrane-based therapeutic plasma exchange was utilized. Following aggressive lowering of the triglycerides, there was an immediate resolution of the pseudo-hypobicarbonatemia and anion gap metabolic acidosis. Recognition of lipemic serum in the setting of an otherwise unexplained anion gap metabolic acidosis should prompt the clinician to obtain a blood gas sample for true determination of the acid-base status. Doing so may avoid an extensive and expensive metabolic work-up.

Retrospective analysis on clinical data and genetic variations of patients with beta-ketothiolase deficiency

To summarize the clinical, biochemical and molecular characteristics of 8 patients with beta-ketothiolase deficiency (BKD). Clinical characteristics, biochemical markers detected by tandem mass spectrometry (MS-MS) and gas chromatography-mass spectrometry (GC-MS), and variations of ACAT1 gene of the 8 patients were reviewed. Three patients were diagnosed by newborn screening and were asymptomatic. Five patients showed dyspnea and metabolic acidosis through high risk screening. Blood methylcrotonyl carnitine (C5:1) were 0.43 (0.20-0.89) μmol/L and 3-hydroxyisovaleryl carnitine(C5-OH) were 1.37 (0.98-3.40) μmol/L. Both were significantly higher than those of healthy controls (P<0.01). Urinary 2-methyl-3-hydroxybutyric acid was 56.04 (7.69-182.20) and methylcrotonyl glycine was 42.83 (9.20-127.01), both were higher than normal levels. In 5 patients urinary 2-methyl-3-hydroxybutyric acid level was remarkably decreased (P<0.05) after treatment. Analysis of ACAT1 gene mutation was performed in six families. Missense variations were detected in 78.6% of the cases. 42.8% of the 7 BKD patients have carried c.1124A>G (p.N375S) variant, which accounted for 28.6% of all 14 mutant alleles. Four novel variants, namely c.229delG (p.E77KfsTer10), c.373G>T (p.V125F), c.419T>G (p.L140R) and c.72+1G>A, were discovered. Pathogenicity assessment of two highly conservative missense variants (p.V125F) and (p.L140R) were 0.994 and 1.0 (Scores obtained from PolyPhen2), and PROVEAN scores were -4.652 and -5.399, respectively. c.72+1g>a was suspected (by Human Splicing Finder) to alter the wild type donor motif and most probably affect the splicing. Clinicians should consider MS/MS and GC/MS testing for those with unexplained neurological symptoms and metabolic acidosis in order to attain early diagnosis of BKD. Genetic testing should be used to confirm the diagnosis.

Two Cases of Ethylene Glycol Poisoning Treated Successfully with Haemodialysis

Introduction: Ethylene glycol is an organic toxic compound found in many household items including radiator coolants and brake oil. Toxic effects of ethylene glycol are due to its metabolites glycolic acid and oxalic acid which cause potentially fatal metabolic acidosis and renal failure. Here we discuss two cases of ethylene glycol poisoning with literature review on pathophysiology, clues in diagnosis and therapy. Case presentations: First case is of a teenage girl presenting with unexplained persistent drowsiness. She went on to develop acidotic breathing and anuria. Unexplained metabolic acidosis and acute kidney injury inclined us towards ethylene glycol poisoning. On further questioning, she confirmed taking radiator coolant 5 hours before admission. The second case is of a young automobile serviceman who presented with unexplained markedly reduced level of consciousness. He had high anion gap metabolic acidosis, calcium oxalate crystals in urine and basal ganglia hypodensities in non-contrast CT. He later developed acute kidney injury. Ethylene glycol poisoning was suspected which was later confirmed when the patient regained consciousness. Both patients responded well to haemodialysis and recovered without complications. Discussion: Ethylene glycol is an easily accessible toxic compound that can be used as a suicidal agent. High anion gap metabolic acidosis, acute kidney injury, calcium oxalate crystalluria and altered sensorium are highly suggestive. Conclusions: A high degree of suspicion is needed for early diagnosis. Haemodialysis can be used effectively to remove the toxic metabolites and treat the renal impairment. Early recognition will save lives without long term renal or neurologic complications.