ODP221 Late-Onset Hypoglycemia in a Patient with Fatty Acid Oxidation Disorder

Abstract

Abstract Background Multiple acyl-CoA dehydrogenase deficiency (MADD) is a disorder of fatty acid and protein metabolism due to a defect in electron transfer flavoprotein or in electron transfer flavoprotein dehydrogenase, and can present with hypoglycemia as a component of its clinical phenotype. We describe a rare case of hypoglycemia due to MADD with unusually late onset at age of 63 years. Clinical case: 63-year-old female with history of hypertension and depression, admitted to the hospital with a several month history of progressive weakness resulting in inability to walk, lightheadedness, unintentional 40-pound weight loss and oropharyngeal dysphagia to solids. On exam, she was noted to have predominant cranial neuropathies and proximal muscle weakness. Patient was found to be hypoglycemic to 47 mg/dL [75-200], with a lactic acidosis of 2.1 mmol/L [0.5-1.9], elevated CK of 630 U/L [22-269], elevated aldolase of 12.7 U/L [1.5-8.1], and increased beta-hydroxybutyrate of 2.9 mmol/L [<0.3] along with transaminitis without cholestatic pattern. Fasting insulin level was 6 uIU/mL [3-19], C-peptide was low normal 1.1 ng/dl [0.8-3.5] with corresponding glucose of 57 mg/dl. Proinsulin level and sulfonylurea panel were unremarkable, and insulin antibodies were negative. Adrenal insufficiency was ruled out with normal cosyntropin stimulation test. IGF-1 and IGF-2 levels were also within normal limits. CT scan of the head, abdomen and pelvis did not evidence any issues. Furthermore, prior to this admission, patient had extensive work-up done for generalized weakness including evaluation for myasthenia gravis, myositis, HIV, thyroid disease, and other autoimmune conditions which was unrevealing. A muscle biopsy was performed with patology suggestive of a lipid storage disorder. Genetic testing only demonstrated variants of uncertain significance in LARGE1, PLEC and TTN genes. Additional testing revealed elevated serum concentrations of short, medium and long chain acylcarnitine species. Urinary organic acids were also increased with predominant elevation of 2-hydroxy-glutaric, ethylmalonic, adipic and suberic acids. This pattern, along with increased plasma acylcarnitine is typically associated with multiple acyl-CoA dehydrogenase deficiency. Serum free fatty acids were also high, supportive of MADD as previously reported in some cases. She was started on high-dose riboflavin replacement and advised to ingest a low-fat, low-protein diet, with frequent feeding and blood glucose monitoring. Conclusion MADD is a rare cause of hypoglycemia in adults. It is important to consider this condition as a differential diagnosis of hypoglycemia associated with generalized weakness even in older individuals. Presentation: No date and time listed