A Sweet but Lethal Disease

First Author: Joann Chang

Co-authors: Shawn McCandless, M.D. and Debra Leizman, M.D.

Introduction: Branched-chain ketoacid dehydrogenase deficiency (also known as maple syrup urine disease or MSUD) is an inborn error of metabolism that renders a person incapable of breaking down branched chain amino acids: isoleucine, leucine, and valine. The resulting accumulation of ketoacids causes severe metabolic acidosis; hyperleucinemia is particularly problematic because leucine accumulating in the CNS leads to a toxic encephalopathy. Once a fatal disease in infancy, these patients are now leading longer lives due to newborn screening, maintenance with special diets, and aggressive management of metabolic decompensation.

Case: Two days prior to admission at a tertiary care center, a 38-year-old man with MSUD and intellectual disability was complaining of abdominal pain and had a temperature of 37.9°C. He received bismuth subsalicylate, acetaminophen, and pedialyte at home with modest improvement, but remained lethargic and was taken to a regional hospital. Renal function panel and arterial blood gas revealed severe metabolic acidosis with anion gap of 31: pH 6.76, pCO2 34.5, pO2 99.4, bicarbonate 4.6. Patient was immediately given bicarbonate and IV fluids. In an attempt to find the source of the decompensation, a chest xray and CT abdomen were done. Chest xray was unremarkable, but CT abdomen showed gaseous distention of colon and possible pneumatosis intestinalis in the ascending colon. Once transferred to the tertiary care center, patient was admitted to the MICU where treatment consisted of IV fluids and dextrose, fat emulsion infusion, isoleucine, valine, and a dietary formula to reduce hyperleucinemia by triggering anabolism. After five days, patient's serum levels of leucine began decreasing and GI pain also resolved without intervention. The patient was discharged home on his usual home formula with instructions for follow up with his outpatient Genetics provider.

Discussion: Individuals with MSUD controlled on a daily basis with nutritional management may experience episodes of metabolic intoxication caused by increased catabolism of endogenous protein that may be induced by intercurrent illness or by exercise, injury, surgery, or fasting. Clinical manifestations include epigastric pain, vomiting, anorexia, and muscle fatigue. Pneumatosis intestinalis is not a known association of MSUD. Clinicians must be able to recognize that a simple cold or GI infection can quickly turn life threatening. MSUD patients are at risk for complications due to their ketoacidosis and for encephalopathy. Treatment consists of IV fluids and dextrose, correction of hyponatremia, and dietary supplementation of fats, isoleucine, and valine. Patients with MSUD have a remarkable ability to recover from metabolic crises and a quick conversion to an anabolic state can make all the difference for these patients.

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