ECMO for Metabolic Crisis in a Patient with Mitochondrial Disease

Patients with mitochondrial disease exhibit disrupted pyruvate oxidation, resulting in intraoperative and perioperative physiologic derangements. Increased enzymatic conversion of pyruvate via lactate dehydrogenase during periods of fasting or stress can lead to metabolic decompensation, with rapid development of fatal lactic acidosis. We describe the intraoperative management and postoperative critical care of a patient with mitochondrial disease who presented for repair of esophageal perforation following repair of a paraesophageal hernia. His surgery was complicated by the development of metabolic crisis and severe lactic acidosis which became resistant to conventional therapy before ultimately resolving with the initiation of venoarterial extracorporeal membrane oxygenation (VA-ECMO).

Continuous Glucose Monitoring in the Management of Hypoglycemia in TANGO2

Introduction: The TANGO2 gene encodes a transport and Golgi organization protein of unclear function; mutations should be considered in patients presenting with acute metabolic crisis, hypoglycemic episodes, cardiac arrhythmias, and other endocrinopathies. We report the novel use of a continuous glucose monitor (CGM) to help predict and prevent significant hypoglycemic episodes in a patient with TANGO2 mutation. Clinical Case: A 14-month old previously healthy, developmentally normal female who presented with unresponsive hypoglycemia (glucose 26 mg/dL) was demonstrated by Next Generation Sequencing to have a pathogenic 31.8 kb deletion of exon 3 to 9 in the TANGO-2 gene and a suspected pathogenic hemizygous c.569_592dup, p.Ile190_Leu197dup in TANGO-2. Her hospital course was notable for MRI showing hypoxic ischemic encephalopathy and both physical and electrical cardiac dysfunction. Continuous intravenous dextrose corrected the hypoglycemia, and transient hyperglycemia followed after several days of a glucose infusion rate between 3.2 to 5.8 mg/kg/min. After transitioning to ad lib oral feeds without restrictions, she was discharged. A second admission for acute unresponsive hypoglycemia and metabolic acidosis (glucose 30 mg/dL) occurred at 17 months of age with no clear inciting cause. Continuous IV dextrose at 9.9 mg/kg/min corrected the hypoglycemia and again resulted in transient hyperglycemia up to 271 mg/dl. Levothyroxine was also started for a TSH of 27 mIU/mL and a T4 of 4.6 ug/dL. Immediately after discharge, a DexCom G6 CGM was placed. Data over 2 weeks shows an average glucose of 104 ng/dL with 99% of the BS in target range. Parents report that CGM predictive low alerts have allowed intervention to abort fasting-related metabolic crises. Conclusion: In TANGO-2 deficiency, the liver may not adequately store and/or release glycogen in response to glucagon due to abnormal endoplasmic reticulum, Golgi apparatus, and mitochondrial functioning in states of stress or illness. Recent reports are conflicting with some showing reduced mitochondrial respiration in TANGO-2 patients in steady state with others finding normal values, opening the possibility that a combination of factors in the setting of stress may precipitate a metabolic crisis. Our patient quickly returns to near-normal physiological functioning; consequently, we suggest that use of a CGM can help prevent fasting related metabolic crisis in TANGO2 patients and can help guide feeding schedule and food choices to limit hyper- and hypoglycemia. In addition, CGM data can help further investigate if any beta cell dysregulation exists in non-acute states. References: Bérat CM, ... & de Lonlay P. (2020). Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises.... J Inherit Metab Dis. 2020 Sep 14. doi: 10.1002/jimd.12314.

Evaluation of Neonatal Acute Metabolic Crisis in Maple Syrup Urine Disease with MR Diffusion and MR Spectroscopy: Case Series and Review of the Literature

Magnetic resonance imaging (MRI) findings of acute metabolic crisis in maple syrup urine disease (MSUD) in neonates were reviewed. This case cohort study included six MSUD neonates imaged during acute metabolic decompensation. Specific diffusion imaging and proton spectroscopic findings were reviewed. All patients revealed extensive intramyelinic cytotoxic edema typically involving myelinated white matter structures. Brainstem, cerebellar white matter and peduncles, midbrain, posterior limbs of internal capsules, central portions of periventricular, and perirolandic white matter regions showed typical MSUD edema. Gray matter structures such as dentate nucleus and thalamus were involved in all patients. Involvement of other deep nuclei was also noted in a few patients. None of the patients showed involvement of the superficial cortex. Reduction in N-acetyl aspartate, a prominent lactate peak, and a peak representing methyl groups of amino acids were characteristic findings seen on intermediate short echo time MR spectroscopy. Our case series outlines the importance of diffusion and spectroscopy MR techniques in the diagnosis of acute neonatal MSUD metabolic crisis.

Lifestyle, Nutritional and Psychological Changes in Adult Patients with Inborn Errors of Metabolism during COVID 19 Pandemic: Resultss from an Online Survey

When COVID-19 pandemic out broke in Italy, during the lockdown from March to May 2020, Inborn Errors of Metabolism (IEM) patients were at risk of not getting their dietary special products and routine visits. Moreover, during pandemic, psychological difficulties might have arose in these subjects, even more severe than in the general population due to the worries about acute decompensation caused by a possible COVID-19. In order to evaluate the patients’ perception of the outbreak situation and their related needs, three simple online anonymous surveys drawn up by Google Forms were sent to patients and families referring to our Adult IEM Center. Answers were collected between April and May 2020. Questionnaires investigated nutritional and lifestyle changes and psychological status using validated psychological tools. 19 patients with IEM filled out our survey (Median age 26-30 years). The most common nutritional therapy was low protein diet. During quarantine 12% patients failed to follow their usual medical diet, 65% reduced their physical activity and no one underwent an acute metabolic crisis. 57% of patients asked for more frequent access to the reference center. 33% of patients showed stress perceived of clinical relevance and general health perception were out of normal in 40% of patients. In conclusion, during quarantine some patients reported difficulty in following their medical diet or physical activity and were clinically stressed. Despite this, no one experienced a metabolic crisis, but asked for contacting the Metabolic Team in different ways than usual due to worries about their health condition. Telemedicine, the possibility of clinical follow-up at home patient (Including blood tests) and reservation of non-COVID-19 beds for hospital admission of IEM patients may have contributed to help IEM adult patients in better face this emergency time.

Exacerbation of myopathy triggered by antiobesity drugs in a patient with multiple acyl-CoA dehydrogenase deficiency

Background Multiple acyl-CoA dehydrogenase deficiency (MADD) is a treatable lipid metabolism disorder that presents as myopathy and episodic metabolic crisis. The metabolic crisis is typically associated with prolonged fasting or physical stress; however, the mechanism of metabolic crisis is not yet fully understood. Case presentation A 28-year-old Taiwanese woman presented with dyspnoea, poor appetite, and muscle weakness after using antiobesity drugs, including metformin, triiodothyronine, and topiramate. MADD was diagnosed, and her symptoms rapidly improved after treatment with riboflavin, carnitine, and ubiquinone. To date, antiobesity drugs have not been reported to be a provoking factor in fatty acid oxidation disorder. Conclusions The increase of β-oxidation activity due to antiobesity drugs supports the hypothetical substrate competition model for MADD metabolic crisis. Because the drugs our patient used are commonly prescribed, we report this case to increase the vigilance and proactivity of clinicians in recognising this treatable adult-onset myopathy.

Anaesthetic considerations in a child with methylmalonic acidemia and its literature review

Methyl malonyl coenzyme A mutase deficiency is a rare autosomal inherited inborn error in branched-chain amino acid metabolism characterised by the accumulation of methylmalonic acids. There is relative paucity of literature regarding anaesthetic management of these children presenting for incidental major abdominal surgery. Preoperative management includes goal-directed correction of dehydration, metabolic acidosis and hyperammonemia. Anaesthetic goals include avoidance of factors that can trigger metabolic crisis like hypercapnia, hypothermia, hypoxia, surgical stress, hypovolaemia, hypotension and so on. Herein, we are reporting the anaesthetic management of a 17-month-old child with methylmalonic acidemia (MMA) posted for a major upper abdominal surgery for excision of an adrenal mass, which was incidentally diagnosed during admission for an episode of metabolic crisis. We aim to highlight the specific nuances of pathophysiology of the disease, preoperative optimisation, anaesthetic considerations, role of advanced monitoring and regional anaesthesia and current literature on the management of patients with MMA.

SARS-CoV-2 infection in a patient with propionic acidemia

We describe a 14-month-old boy, with a previous diagnosis of propionic acidemia (PA) by expanded newborn screening, who, admitted for a suspected metabolic crisis, tested positive for SARS-CoV-2. Since propionic acidemia was diagnosed, the patient has followed the recommended diet for this inborn error of metabolism. Although propionic acidemia patients are at a high risk of suffering metabolic crises, frequently associated with permanent clinical complications, psychomotor development of this patient was normal. The SARS-CoV-2 infection (at about 1 year of age) caused the patient’s first metabolic crisis. However, his clinical course was in keeping with a mild clinical form of COVID-19, and he recovered without experiencing severe clinical consequences. We describe this patient in order to improve the knowledge about follow up of PA patients identified by newborn screening and to increase the limited number of reports of SARS-CoV-2 infection in children with comorbidities, especially inborn errors of metabolism.