Metabolic Acidosis Research Articles

8075 Euglycemic Diabetic Ketoacidosis Associated With Cocaine Use

Abstract Disclosure: N.N. Solanki: None. A.N. Kiani: None. M. Feldman: None. Euglycemic diabetic ketoacidosis (EDKA) is characterized by increased anion gap metabolic acidosis, ketonemia or ketonuria, and normal blood glucose levels (<200 mg/dL). Due to the absence of hyperglycemia, it commonly presents as a diagnostic and therapeutic dilemma. EDKA is commonly associated with decreased caloric intake, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, recent use of insulin, heavy alcohol consumption, chronic liver disease, glycogen storage disorders, and drug-induced intoxication. Cocaine use is a lesser-known etiology for EDKA. We present a case of a 64-year-old female with a history of type 2 diabetes mellitus who presented with complaints of decreased oral intake for two days secondary to nausea and vomiting and productive cough for one week, along with cocaine use. Despite an extensive history of diabetes and no recent SGLT-2 inhibitor use, her labs were consistent with euglycemic DKA. Her imaging and further investigations revealed respiratory syncytial virus pneumonia. The patient was initially managed for starvation ketoacidosis with fluid resuscitation with no improvement in acidosis and later treated with DKA protocol with rapid correction of her anion gap metabolic acidosis. This case highlights the challenges associated with diagnosing and treating EDKA. Early initiation of DKA protocol should be considered in diabetic patients presenting with euglycemia with high anion gap metabolic acidosis with a clinical picture of starvation and cocaine use. Presentation: 6/3/2024

6695 When Pheochromocytoma Presents As Acute Renal Failure, With Complete Resolution, A Case Report

Abstract Disclosure: U.A. Siddiqui: None. D. Deyar: None. D. Bondarenko: None. M. Ahmad: None. K.K. Lessard: None. Pheochromocytomas and paragangliomas (PPGL), are rare neuroendocrine tumors (0.66/ 100,000 cases), often characterized by paroxysmal hypertension and associated symptoms. While cardiac complications have been well-documented in the literature, there is limited information regarding acute renal failure. We explore a unique case of pheochromocytoma presenting initially with hypertensive crisis, but also with an unexpected journey into acute renal failure and subsequent recovery. 62-year-old hispanic male without known past medical history presents to the emergency department with chest pain, epigastric pain, dyspnea, and emesis. He was tachypneic, febrile (101°F), hypoxic (83% on room air), and profoundly hypertensive (188/112 mmHg). CT scan showed pneumonia as well as a 7cm complex mass within the left adrenal gland. Admitting labs showed metabolic acidosis, acute kidney injury (Cr 2.52mg/dL) and elevated troponins. Echocardiogram showed a reduced ejection fraction 45-50% and coronary angiography showed mild nonocclusive coronary artery disease. MRI visualized a solid left adrenal mass measuring 6.8cm with enhanced, mixed T1/T2 signaling and drop out inconsistent with adenoma. Adrenal labs revealed ACTH 125 pg/mL (9-46 pg/mL) and cortisol 27mcg/dL free metanephrine (MN) 1,422 pg/mL (<57 pg/mL), and free normetanephrine (NMN) >20,000 pg/mL (<148 pg/mL), total free MN + NMN >40,000 pg/mL (<205 pg/mL). Preoperative MIBG scan showed increased tracer activity of the left adrenal consistent with pheochromocytoma. Alpha blockade was performed using doxazosin and carvedilol was continued. Unfortunately, he developed oliguria and rising creatinine ( 7.4mg/DL). Kidney biopsy showed findings of acute tubular necrosis and mild fibrosis. Hemodialysis was initiated, receiving 12 sessions prior to undergoing open left adrenalectomy with mass resection on day 22 of admission. Post-operative blood pressure was managed with volume re-expansion and tapering of alpha blocker. Within 72 hours, renal function fully recovered and dialysis was discontinued. Follow up metanephrines are within normal limits and genetic testing results remain pending. Cases of acute renal failure and PPGL are scarce, and this case report contributes to the topic. Mortality in p is usually due to cardiovascular complications such as stroke, cardiomyopathy, and dysrhythmia [2]. Renal complications result from hypertensive nephrosclerosis or nephrotic syndrome. To date, only one case report from 1961 exists on acute tubular necrosis and PPGL [3]. We present an interesting case of pheochromocytoma complicated by hypertensive crisis and acute renal failure requiring dialysis. Resection of the pheochromocytoma normalized renal function. This demonstrates the importance of timely resection of the tumor and meticulous blood pressure management to ensure optimal outcomes. Presentation: 6/2/2024

12201 Ketogenic-diet As A Trigger Of First Episode Diabetic Ketoacidosis In A Woman Living With Type 1 Diabetes Mellitus

Abstract Disclosure: M.E. Chacon Cruz: None. A.N. Gonzalez Bossolo: None. G.J. Mora Osoria: None. A number of dietary patterns have been proposed as an effective method for weight reduction. A keto diet is a strict low-carbohydrate and high-fat diet. The reduction in carbohydrates enables the body to rely on fat as a predominant energy source leading to a state of ketosis. However, a serious but rare complication of the ketogenic diet is ketoacidosis associated with low carbohydrate intake, which should be cautiously monitored in people with a predisposition to the condition, such patient with diabetes mellitus type 1. We report the case of a female patient living with type 1 diabetes mellitus female who developed her first episodes of diabetic ketoacidosis (DKA) as the following the course of ketogenic diet. A 53 y/o Female patient with past medical history diabetes mellitus type 1 and pernicious anemia went emergency department complaining pelvic pain associated with weakness, nausea and vomiting for about 1 day of evolution. Patient also refers that during the past 2 weeks she has been doing a detox and taking some herbal and tea. Other physical examinations were unremarkable except for moderate dehydration. The initial testing revealed patients meet criteria for severe diabetes ketoacidosis (DKA) with a pH: 7.04, CO2 15, serum central bicarbonate in 6 mmol/L and elevated blood glucose in 504 mg/dl and positive urine and serum ketones, C-Peptide less than 0.02 ng/ml. and glycosylated hemoglobin in 8.25%. She was admitted to the intensive care unit and treated with intravenous saline, intravenous insulin infusion, and electrolyte repletion. Blood glucose levels and metabolic acidosis improved. After DKA resolved patient refers that week started with Keto-diet and was restricting carbohydrates. Patient was discharge home with multiple injection insulin and followed by Endocrinologist services in the external clinic for a follow up. This case illustrates the challenges and the importance of dietary history providing clues to the diagnosis. If we had never asked her about her diet, we would not have found the reason that brought her to the DKA. This case demonstrates the development of DKA following ketogenic diet in a patient with type 1 diabetes. It is important for physicians to be aware of this rare potential complication of ketogenic diet which is infrequently reported in literature. Therefore, physicians should be cognizant of the complications and risks, and benefits of the ketogenic diet. Risks and benefits of the ketogenic diet should be discussed with patients before initiation of this diet. The patient was followed in an outpatient clinic with Endocrinologist service for evaluation for an insulin pump. Presentation: 6/1/2024

6541 Recurrent Euglycemic Diabetic Ketoacidosis And Myonecrosis In A Patient Previously Thought To Have Type 2 Diabetes Mellitus

Abstract Disclosure: K. Haridas: None. M.M. McConnell : None. Introduction: Euglycemic diabetic ketoacidosis (DKA) is a well-recognized complication with the use of sodium linked cotransport of glucose-2 (SGLT2) inhibitors. Diabetic myonecrosis is a rare complication of diabetes mellitus caused by spontaneous death of muscle due to microvascular ischemia. Clinical Case: A 48-year-old male diagnosed with Type 2 Diabetes Mellitus with HbA1c 11.3%, treated with Empagliflozin and basal-bolus insulin was admitted to the hospital with left thigh pain and anorexia. Physical examination was notable for BMI of 19kg/m2 and left lateral thigh induration. Laboratory evaluation revealed venous pH 7.1, bicarbonate 10mmol/L (20-30), anion gap 32mmol/L(8-12), glucose 168mg/dl (65-99), ESR 67mm/h (<=12), Creatinine Kinase 31 U/L (63-473), glucosuria (4+) and ketonuria (4+). He was diagnosed with euglycemic DKA due to SGLT2 inhibitor. He was also diagnosed with Type 1 Diabetes Mellitus (T1DM) based on undetectable C-peptide and GAD antibody titer 64.3IU/ml(<5). MRI of the left thigh revealed an area of diabetic myonecrosis, measuring 11cm. He was treated with continuous insulin infusion. On hospital day 3, after resolution of the anion gap metabolic acidosis, transition was made to basal-bolus insulin. On hospital day 5, recurrent euglycemic DKA was diagnosed with bicarbonate 15mmol/L, anion gap 18mmol/L, beta-hydroxybutyrate 49.6mg/dl (<=3mg/dl), glucose 185mg/dl, glucosuria (4+) and ketonuria (4+). Continuous insulin infusion was restarted. On hospital day 8, transition was made to subcutaneous insulin. Diabetic myonecrosis was initially managed conservatively with analgesics, aspirin, and physical therapy. Due to worsening leukocytosis on hospital day 13, Ceftriaxone was started and surgical debridement was performed, revealing a loculated abscess within necrotic muscle. Empagliflozin was discontinued at discharge. Discussion: The risk of euglycemic DKA with SGLT2i use is increased in patients with T1DM and decreased oral intake, and insults like trauma or surgery as seen in this patient. Although the half-life of empagliflozin is 12 to 14 hours, there have been case reports of persistent or recurrent euglycemic DKA for 7-12 days from the time of last dose. The continued glucosuria and ketonuria in this patient with serum glucose levels below the renal threshold confirmed the recurrence. Diabetic myonecrosis usually affects the muscles of the proximal lower extremities and is seen in patients with poorly controlled diabetes with microvascular complications, between one and two decades after diagnosis, as in this patient. Conclusion: A high index of suspicion for recurrent euglycemic DKA must be maintained in patients who have new or persistent high anion gap metabolic acidosis until 2 weeks from last dose of SGLT2 inhibitor. Diabetic myonecrosis, especially if complicated by abscess formation, may require surgical intervention. Presentation: 6/1/2024

8676 Hereditary Fructose Intolerance Unmasked: Report of a Pediatric Case Exploring Differential Diagnosis of Hypoglycemia and Genetic Insights

Abstract Disclosure: N. Solano: None. D. Baboun: None. A. Granados: None. A. Carrillo-Iregui: None. Introduction: Hereditary fructose intolerance (HFI) is an uncommon autosomal recessive metabolic disorder characterized by a deficiency of aldolase B, a crucial enzyme involved in fructose metabolism. This deficiency causes an accumulation of fructose-1-phosphate, which triggers a cascade of metabolic disturbances including hypoglycemia, lactic acidosis, and hepatic dysfunction. If left untreated, HFI can lead to severe complications, including liver failure and even death. Diagnosing HFI can be challenging due to its nonspecific clinical presentation and the absence of routine screening tests. Case presentation: A 4-year-old girl was referred from an outside hospital for hypoglycemia requiring intravenous dextrose infusion. The patient became lethargic 30 minutes after consuming a honey-based cough syrup. Upon presentation to the emergency department, her blood glucose level was 41 mg/dL. Her past medical history revealed an episode of lethargy and persistent vomiting at age 21 months, coinciding with an intussusception. A finger blood glucose test at the time was undetectable, and further evaluation revealed metabolic acidosis, elevated liver enzymes, and a normal ammonia level. Plasma amino acid, acylcarnitine, carnitine, urine acylglycine, carnitine, and urine organic acid levels were all within normal limits. Fatty acid oxidation and glycogen storage disease panels were also negative. On inquiry into her dietary habits, her parents recalled she would spit fruits out whenever tasting them, suggesting an innate aversion to fructose-rich foods. Initial comprehensive inpatient workup, including a critical sample, yielded no definitive results. She underwent a strict 24-hour inpatient fast and remained asymptomatic, with blood glucose levels above 65 mg/dL, ruling out hyperinsulinism. A broader next-generation sequencing (NGS) hypoglycemia panel was ordered, which identified a heterozygous pathogenic variant, c.178C>T (p.Arg60*) maternally inherited, and a likely pathogenic variant, c.379+1G>T (Splice donor) paternally inherited, in the aldolase B gene. Both confirmed the diagnosis of hereditary fructose intolerance (HFI). The family received comprehensive dietary and genetic counseling. Conclusion: HFI is an uncommon but potentially life-threatening inborn error of metabolism. Maintaining a high index of suspicion, considering a broad differential diagnosis, and obtaining a detailed dietary history, including fruit consumption, are crucial for identifying and managing HFI in infants and children with unexplained hypoglycemia. This case highlights the importance of early diagnosis and dietary intervention to prevent severe complications in patients with HFI. Additionally, it emphasizes the need for comprehensive dietary counseling and education for patients' families to ensure lifelong adherence to a fructose-restricted diet. Presentation: 6/2/2024

7491 Post operative Euglycemic Diabetic Ketoacidosis in Type 2 Diabetic patient - A diagnostic challenge

Abstract Disclosure: S. Azmat: None. O. Lodhi: None. H. Ashok: None. M.F. Siddiqui: None. Euglycemic Diabetic Ketoacidosis (EDKA) is a rare but potentially fatal condition that is often difficult to diagnose as underlying ketoacidosis is masked by euglycemia. The diagnosis and management of this condition requires a swift and comprehensive approach to avoid delay. We report a case of 66-year-old female with Insulin-dependent Type 2 DM who developed postoperative euglycemic diabetic ketoacidosis, highlighting the significance of maintaining a high degree of suspicion for EDKA in postoperative patients, whose surgical course may obscure the underlying diabetic ketoacidosis symptoms. Clinical Case: A 66-year-old female with past medical history of Insulin dependent Type 2 DM presented to the emergency department with severe epigastric pain. CT Abdomen revealed perforated gastric ulcer with pneumoperitoneum requiring urgent laparoscopic graham patch repair. Patient’s outpatient medications include Lantus and metformin. She had mild hyperglycemia on admission with blood glucose of 176 mg/dL (140-160mg/dL) without metabolic abnormality. Insulin administration was omitted due to pre and post operative normoglycemia. The patient was NPO followed by initiation of nasogastric tube feeds. Postoperative course was complicated by hypotension, generalized abdominal discomfort and anion gap metabolic acidosis. Graham patch failure, abdominal infection, and post-surgical complications were systematically ruled out. Patient continued to decline with worsening anion gap metabolic acidosis; pH of 7.18 (7.35-7.45), HCO3 < 10 mEq/L (21 mEq/L - 31 mEq/L), anion gap15 mmol/L (8 to 12 mmol/L), blood sugar (147-208 mg/dl). There was no lactic acidosis or renal impairment. Beta hydroxybutyrate levels were elevated at > 4.5 mmol/L. Thus diagnosis of euglycemic DKA was established and treated with insulin drip per DKA protocol and dextrose fluids. EDKA resolved within five days with clinical improvement. She was transitioned to subcutaneous basal bolus insulin. She remained euglycemic and and had good surgical outcomes.Discussion: Euglycemic DKA is rare with only 2.6% to 3.2% of DKA, presenting as euglycemic. It presents as unique diagnostic challenge due to atypical DKA presentation with blood glucose less than 250 mg/dL. The primary driver for EDKA is either a reduction in hepatic glucose production at times of fasting or the overabundance of counter-regulatory hormones resulting in excess glucosuria. Literature has reported the effects short-term fasting on developing EDKA and starvation induced ketosis secondary to extreme ketogenic diets or bariatric surgery primarily among Type 1 diabetics. Clinically patients may exhibit symptoms similar to classic DKA, however, this classic picture may be confounded in a critically ill post-surgical patient, thus delaying recognition. This emphasizes the importance of including EDKA in differentials while evaluating such patients. Presentation: 6/1/2024

Suggested guide to using lactate gap as a surrogate marker in the diagnosis of ethylene glycol overdose.

Ethylene glycol (EG) poisoning, if not diagnosed rapidly, can lead to poor patient outcomes. Gas Chromatography (GC) is primarily used for EG quantitation which is rarely available, and the turn-around time may be prolonged. Most lactate results from point-of care (POCT) methods are falsely elevated in EG poisoning compared with automated chemistry analyser results. In combination the lactate gap (POCT-Automated chemistry) can be used as surrogate marker in just about all laboratories to indicate likely EG toxicity and guide treatment. A male presented by ambulance to hospital with severe agitation requiring mechanical ventilation to facilitate ongoing management. Venous blood gas analysis confirmed a high anion gap metabolic acidosis (HAGMA) with an elevated lactate. The lactate and osmolarity measured in the laboratory showed a normal lactate and high osmolarity, giving a large osmolar gap. The patient was immediately commenced on renal replacement therapy for presumed EG poisoning to minimize kidney injury, and the treatment continued for 19 hours. A very high EG concentration was confirmed by GC the next day. An elevated lactate gap along with a HAGMA and osmolar gap can provide rapid surrogate laboratory data indicating EG poisoning enabling timely treatment and better patient outcomes.

Paradoxical metabolic acidosis after vomiting in children with spinal muscular atrophy: A report of 9 patients

BackgroundSpinal muscular atrophy (SMA) is a hereditary neuromuscular disease that progresses toward restrictive respiratory failure due to muscle paralysis. We observed that SMA patients presented with a specific clinical and laboratory profile, consisting of severe metabolic acidosis following an episode of mild vomiting. This is an unusual, little-known, and life-threatening situation for these patients, as hyperventilation induced by metabolic acidosis can lead to exhaustion and to death by mixed acidosis. ObjectiveThe aim of our study was to describe this paradoxical acidosis after vomiting in SMA patients and to discuss the physiological basis of this condition. MethodsWe conducted a retrospective single-center study reviewing the clinical and laboratory data of SMA patients who were hospitalized in the intensive care unit for severe metabolic acidosis after vomiting. ResultsOur cohort comprised 11 cases. On arrival, the median pH of the patients was 7.23 with a median bicarbonate concentration of 11.7 mmol/L and almost half of them (45 %) had ketone bodies in the blood and/or urine. The median correction time was 24 h for pH and 48 h for bicarbonate concentrations after receiving intravenous hydration with a glucose solution. ConclusionsWe suggest that SMA patients are particularly sensitive to ketoacidosis induced by fasting, even after a few episodes of mild vomiting. Moreover, they have a low buffering capacity due to their severe amyotrophy, which favors metabolic acidosis. They must be quickly hydrated through a glucose-containing solution to avoid exhaustion, mixed acidosis, and death.

Hyperchloremic metabolic acidosis potentially benefiting sodium bicarbonate therapy: A multi-center cohort study

BackgroundThe use of sodium bicarbonate for metabolic acidosis has been a topic of debate, primarily due to the lack of clinical efficacy evidence. This study aims to identify which types of patients with various acid-base balance parameters can benefit from sodium bicarbonate therapy. MethodsPatients diagnosed with metabolic acidosis were screened from a large multi-center critical care database to form a retrospective cohort. Mortality curves, logistic regression analysis, simulation methods, and propensity scores were used to compare data between sodium bicarbonate (SOB group) and non-treated (Non-SOB group) patients. ResultsThere was an interaction between baseline chloride, anion gap levels and sodium bicarbonate therapy on patients' in-hospital death. As chloride levels increased, the in-hospital mortality curves of the SOB group and Non-SOB group gradually converged, with the difference narrowing from approximately 20 % to 10 %, and then gradually widened with the increase of the anion gap. Furthermore, when patients had high chloride levels (≥112 mmol/L), those in the SOB group exhibited a higher incidence of hypernatremia, hypokalemia, and hypocalcemia at 24 h, and a lower incidence of hyperchloremia. Patients in SOB group also had a lower simulated mortality. Among patients treated with sodium bicarbonate, those with low chloride had more difficulty in normalizing pH compared to those with high chloride. ConclusionsThis study identified an interaction between baseline chloride and sodium bicarbonate therapy on patient survival. Hyperchloremic metabolic acidosis may potentially benefit from sodium bicarbonate therapy. Further prospective randomized controlled studies are warranted.

The effect of a low potential renal acid load diet on metabolic acidosis in patients with chronic kidney disease stage 4 and 5

The effect of a low potential renal acid load diet on metabolic acidosis in patients with chronic kidney disease stage 4 and 5

Distal convoluted tubule-specific disruption of the COP9 signalosome but not its regulatory target cullin 3 causes tubular injury.

The disease familial hyperkalemic hypertension (FHHt; also known as Gordon syndrome) is caused by aberrant accumulation of with-no-lysine kinase (WNK4) activating the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT) of the kidney. Mutations in cullin 3 (CUL3) cause FHHt by disrupting interaction with the deneddylase COP9 signalosome (CSN). Deletion of Cul3 or Jab1 (the catalytically active CSN subunit) along the entire nephron causes a partial FHHt phenotype with activation of the WNK4-STE20/SPS1-related proline/alanine-rich kinase (SPAK)-NCC pathway. However, progressive kidney injury likely prevents hypertension, hyperkalemia, and hyperchloremic metabolic acidosis associated with FHHt. We hypothesized that DCT-specific deletion would more closely model the disease. We used Slc12a3-Cre-ERT2 mice to delete Cul3 (DCT-Cul3-/-) or Jab1 (DCT-Jab1-/-) only in the DCT and examined the mice after short- and long-term deletion. Short-term DCT-specific knockout of both Cul3 and Jab1 mice caused elevated WNK4, pSPAKS373, and pNCCT53 abundance. However, neither model demonstrated changes in plasma K+, Cl-, or total CO2, even though no injury was present. Long-term DCT-Jab1-/- mice showed significantly lower NCC and parvalbumin abundance and a higher abundance of kidney injury molecule-1, a marker of proximal tubule injury. No injury or reduction in NCC or parvalbumin was observed in long-term DCT-Cul3-/- mice. In summary, the prevention of injury outside the DCT did not lead to a complete FHHt phenotype despite activation of the WNK4-SPAK-NCC pathway, possibly due to insufficient NCC activation. Chronically, only DCT-Jab1-/- mice developed tubule injury and atrophy of the DCT, suggesting a direct JAB1 effect or dysregulation of other cullins as mechanisms for injury.NEW & NOTEWORTHY CUL3 degrades WNK4, which prevents activation of NCC in the DCT. CSN regulation of CUL3 is impaired in the disease FHHt, causing accumulation of WNK4. Short-term DCT-specific disruption of CUL3 or the CSN in mice resulted in activation of the WNK4-SPAK-NCC pathway but not hyperkalemic metabolic acidosis found in FHHt. Tubule injury was observed only after long-term CSN disruption. The data suggest that disruption of other cullins may be the cause for the injury.

Decoding the Renal Puzzle: Idiopathic Distal Renal Tubular Acidosis in a 23-Year-Old Woman with Nephrocalcinosis and Metabolic Acidosis

Decoding the Renal Puzzle: Idiopathic Distal Renal Tubular Acidosis in a 23-Year-Old Woman with Nephrocalcinosis and Metabolic Acidosis

Euglycemic Ketoacidosis Associated with SGLT-2 Inhibitors in Non-diabetic Patients-A Narrative Review.

Euglycemic ketoacidosis is an acute, life-threatening emergency that is characterized by euglycemia, metabolic acidosis, and ketonemia. It is a well-recognized adverse event in diabetic patients taking sodium-glucose cotransporter-2 inhibitor (SGLT-2 inhibitor). However, there is limited data on SGLT-2 inhibitor-related euglycemic ketoacidosis in non-diabetic patients. The mechanism behind SGLT-2 inhibitor-associated euglycemic ketoacidosis involves a general state of starvation or relative insulin deficiency, which exacerbates the mild baseline ketonemia caused by this class of medications while normoglycemia is maintained. The incidence of euglycemic ketoacidosis will likely increase with the increasing use of SGLT-2 inhibitors for various indications in addition to diabetes mellitus type 2, predominantly for congestive heart failure (CHF). Recognizing the signs and symptoms of this life-threatening condition is essential to treat it effectively. Our objective is to comprehensively revisit the pathophysiology of euglycemic ketoacidosis associated with SGLT-2 inhibitors and the risk factors for the condition, review the available data, and summarize the reported cases of euglycemic ketoacidosis in non-diabetic patients on SGLT-2 inhibitors. Our literature search identified five articles with six cases of euglycemic ketoacidosis in non-diabetic patients who were on SGLT-2 inhibitors for heart failure with reduced ejection fraction. The common risk factor in five out of the six cases was decreased oral intake due to acute illness, fasting, or a perioperative state.

Adverse outcomes and mortality in individuals with eating disorder-related electrolyte abnormalities in Ontario, Canada: a population-based cohort study

Individuals with eating disorders are at a higher risk of electrolyte abnormalities than the general population. We conducted the first representative cohort study assessing whether electrolyte abnormalities in people with eating disorders were associated with mortality and physical health outcomes. This was a retrospective population-based cohort study in Ontario including people aged 13 years or older with an eating disorder and an outpatient electrolyte measure within 1 year (between Jan 1, 2008 and June 30, 2019). An electrolyte abnormality was any of hypokalaemia, hyperkalaemia, hyponatraemia, hypernatraemia, hypomagnesaemia, hypophosphataemia, metabolic acidosis, or metabolic alkalosis. The primary outcome was all-cause mortality. Secondary outcomes were hospitalisation, a cardiac event, infection, acute or chronic kidney disease, fracture, and bowel obstruction. In additional analyses, we examined a younger cohort (<25 years old) and individuals with no previously diagnosed secondary outcome. We involved people with related lived or family experience in the study. 6163 patients with an eating disorder and an electrolyte measure within 1 year since diagnosis (mean age 26·8 years [SD 17·5]; 5456 [88·5%] female, 707 [11·5%] male; median follow-up 6·4 years [IQR 4-9]) were included. Ethnicity data were not available. The most common electrolyte abnormalities were hypokalaemia (994/1987 [50·0%]), hyponatraemia (752/1987 [37·8%]), and hypernatraemia (420/1987 [21·1%]). Overall, mortality occurred in 311/1987 (15·7%) of those with an electrolyte abnormality versus 234/4176 (5·6%) in those without (absolute risk difference 10·1%; adjusted hazard ratio 1·23 [95% CI 1·03-1·48]). Hospitalisation (1202/1987 [60·5%] vs 1979/4176 [47·4%]; 1·35 [1·25-1·46]), acute kidney injury (206/1987 [10·4%] vs 124/4176 [3%]; 1·91 [1·50-2·43]), chronic kidney disease (245/1987 [12·3%] vs 181/4176 [4·3%]; 1·44 [1·17-1·77]), bone fracture (140/1987 [7·0%] vs 167/4176 [4·0%]; 1·40 [1·10-1·78]), and bowel obstruction (72/1987 [3·6%] vs 57/4176 [1·4%]; 1·62 [1·12-2·35]) were associated with an electrolyte abnormality, but not infection or a cardiovascular event. Findings were consistent in young individuals (<25 years old) and those without secondary outcomes at baseline, by eating disorder type, and by sex. Electrolyte abnormalities are associated with death and poor physical health outcomes, supporting the importance of monitoring and possible interventions to prevent adverse outcomes. Findings also call for a refinement of the definition of severity of eating disorder and replication of these findings in other jurisdictions. None.

Characterization of a novel variant in KCNJ16, encoding Kir5.1 channel.

The essential role of the inwardly rectifying potassium channel Kir5.1 (KCNJ16) in controlling electrolyte homeostasis and blood pressure has been demonstrated in human and animal studies. Previous studies have identified several bi-allelic mutations of KCNJ16 in humans, causing severe hypokalemia, renal salt wasting, and disturbed acid-base homeostasis. Here, we identified a novel homozygous variant of KCNJ16, I26T, in an Amish patient affected with polydipsia, developmental delay, and chronic metabolic acidosis with low serum bicarbonate concentration. Subsequently, we generated the rat model with I26T mutation using Dahl salt-sensitive rat (I26T rat) to characterize this variant. The male mutant rats displayed similar blood pressure and electrolyte homeostasis under baseline and with a high salt (4% NaCl) challenge. Blood pH, HCO3 - and renal damage also remained similar between WT and I26T rats after high salt challenge. Additionally, single-channel patch clamp analysis revealed similar channel activity in CHO cells overexpressed with WT and I26T mutant Kir4.1/5.1 channels. In summary, this study reported a novel variant in KCNJ16, namely I26T, which is likely a benign variant and not associated with pathologic phenotype in either human or Dahl salt-sensitive rats, indicating that the type/location of variant should be considered when diagnosing and treating patients with KCNJ16 mutations.

Therapeutic Plasma Exchange Complicated by Hyperchloremic Metabolic Acidosis in a Patient with Myasthenia Gravis and CKD

Therapeutic Plasma Exchange Complicated by Hyperchloremic Metabolic Acidosis in a Patient with Myasthenia Gravis and CKD

Sudden visual loss after COVID-19 infection with diabetic ketoacidosis

We report a case of an atypical optic neuritis (AION) in an adolescent male, diagnosed with diabetic ketoacidosis in the setting of a coronavirus disease 2019 (COVID-19) infection. On the third day of admission, he developed sudden profound visual loss and ocular examination revealed bilateral pale disc edema. Examination and investigations were conclusive of bilateral optic neuritis. Optic neuritis in the setting of pale disc edema was unusual, and the pallor could be due to an episode of AION that was superadded by optic neuritis during the cytokine storm. The patient was given a trial of i.v. steroids. However, the vision loss could be recovered partially only. Thus, through this case report, we would like to highlight the importance of a close follow-up of patients following COVID-19 infection and a possible association of metabolic acidosis in precipitating the episode of optic neuritis.

Severe Metabolic Acidosis in a Patient with Spinal Muscular Atrophy

Severe Metabolic Acidosis in a Patient with Spinal Muscular Atrophy

Extremely Low Birth Weight Infant (Gestational Age of 29 Weeks) With Kabuki Syndrome Type I: Case Report and Literature Review.

This paper aimed to investigate the clinical phenotype of Kabuki syndrome (KS) in premature infants. This paper presents a case of an extremely low birth weight infant (gestational age 29 weeks) with KS1 caused by a variant in the KMT2D gene. The clinical, pathological, and differential diagnostic findings were comprehensively analyzed. A thorough literature review was also performed to enhance the understanding of KS, revealing its unique features and prognostic significance. The infant was a male with a gestational age of 29 weeks and a birth weight of 850 g. He had intrauterine growth retardation, characterized by cleft palate, sacrococcygeal skin depressions, and recurrent metabolic acidosis. Whole-exome sequencing revealed the c.4267C > T (p.Arg1423Cys) variant in the KMT2D gene, which was absent in his parents. The patient was discharged after 67 days of treatment, and he was followed up to 19 months of corrected gestational age, with growth retardation and expression language delay. Ten previous studies on preterm infants were retrieved, with 10 preterm infants. They all had characteristic facial features, such as long blepharophimosis, sparse and lateral 1/3 eyebrows, and large and prominent/cupped ears. Other manifestations were extrauterine growth delay (7/10), abnormal development of the cardiovascular system (7/10), abnormal development of the nervous system (5/10), and cleft palate (2/10). Kabuki syndrome is a rare hereditary disorder involving multiple organs and systems. Genetic assessment for preterm infants with congenital abnormalities is recommended.

Elevated osmol gaps in patients with alcoholic ketoacidosis.

The use of the osmol gap as a surrogate marker of toxic alcohol poisoning is common. Unfortunately, many patients with alcoholic ketoacidosis have elevated osmol gaps and are misdiagnosed with toxic alcohol poisoning. We aimed to characterize the range of osmol gaps in patients with alcoholic ketoacidosis. This was a retrospective poison center study. Data from 24 years were reviewed using the following case definition of alcoholic ketoacidosis: (1) documented alcohol use disorder; (2) presence of urine or serum ketones or an elevated blood beta-hydroxybutyrate concentration; (3) an anion gap ≥14 mmol/L. Potential cases of alcoholic ketoacidosis that failed to fulfill all three criteria were adjudicated by three toxicologists. Exclusion criteria included (1) detectable toxic alcohol concentration, (2) hemodialysis and/or multiple doses of fomepizole, (3) no osmol gap documented, (4) other diagnoses that lead to a metabolic acidosis. Demographics, pH, anion gap, lactate concentration, and osmol gap were extracted. Of 1,493 patients screened, 55 met criteria for alcoholic ketoacidosis. Sixty-four percent were male, and their median age was 52 years. The median osmol gap was 27 [IQR 18-36]. The largest anion gap was 57 mmol/L, and the lowest pH was 6.8. Forty-five (82%) of the patients with alcoholic ketoacidosis had osmol gaps >10; 38 (69%) had osmol gaps >20; 24 (44%) had osmol gaps >30; 11 (20%) had osmol gaps > 40. The large range of osmol gaps in patients with alcoholic ketoacidosis often reaches values associated with toxic alcohol poisoning. The study is limited by the potential for transcribing errors and the inability to identify the cause of the osmol gap. In this retrospective study, patients with alcoholic ketoacidosis had a median osmol gap of 27. Given that alcoholic ketoacidosis is easily and inexpensively treated, proper identification may prevent costly and invasive treatment directed at toxic alcohol poisoning.