Abstract #1408177: Spinal Muscle Atrophy Presenting with Non-Diabetic Ketoacidosis

Abstract

Spinal muscle atrophy (SMA) is an untreatable neurodegenerative disease related to loss of survival motor neuron (SMN) 1 gene resulting in muscle atrophy leading to significant morbidity and mortality. Patients with SMA may present with metabolic disturbances including impaired glucose tolerance, fatty acid metabolism and hyperlipidemia. We present a case of SMA presenting with recurrent metabolic acidosis. 51-year-old female with hypertension, osteoporosis, and SMA (homozygous deletion of exon 7 in the SMN1 gene) with quadriplegia and chronic ventilator dependent respiratory failure was admitted with diarrhea, poor oral intake, nausea, and abdominal pain. She did not report sick contacts or fever and had no history of diabetes. She had similar past episodes of metabolic acidosis with acute illness. Vital signs were BP 135/74mmHg, HR 110/min, RR 20/min, afebrile, and SpO2 96% on room air. On exam she appeared ill and debilitated with dry oral mucosa, + abdominal distension and tenderness with no rebound. Labs showed anion gap metabolic acidosis, Na 136mEq/L, K 3.9mEq/L, Cl 102 mEq/L, CO2 12 mEq/L, Anion gap 22, pH 7.13, Creatinine <0.01mg/dl, glucose 110 mg/dl, 2+ urine ketones, beta hydroxybutyrate 7.39 mmol/L, WBC 23.97 K/ul and HbA1c 5.2%. She was treated for non-diabetic ketoacidosis with IV fluids and fixed dose IV insulin infusion with dextrose infusion in tandem. She had hypernatremia, hypocalcemia, hypophosphatemia and hypokalemia likely due to poor nutrition and dehydration, and with aggressive electrolyte replacement, she showed significant clinical improvement during hospitalisation. Patients with SMA are prone to metabolic derangements e.g. ketoacidosis. Several factors may contribute to ketoacidosis such as decreased muscle mass, defects in endocrine pancreatic function and abnormal fatty acid metabolism regardless of triggering factors. One study investigated glucose metabolism and pancreas development in the Smn (2B/-) intermediate SMA mouse model and type I SMA patients. In mice it demonstrated a dramatic cell fate imbalance within pancreatic islets, with a predominance of glucagon-producing α cells at the expense of insulin-producing β cells and mice displayed fasting hyperglycemia, hyperglucagonemia, and glucose resistance. Similar abnormalities in pancreatic islet cells were seen in deceased children with the severe infantile form of SMA indicating that defects in glucose metabolism may play an important contributory role in SMA pathogenesis. There are no present guidelines to manage this entity, but case reports indicated a role of volume resuscitation and electrolyte replacement for improvement and future prevention by avoiding fasting.