A 6 year‐old previously healthy male presented with altered mental status following a 4‐day history of vomiting and diarrhea. He had significant lethargy and dehydration with an otherwise non‐focal exam. Labs revealed glucose of 52 mg/dL and high anion gap metabolic acidosis with bicarbonate of 7 mEq/L. Head CT was normal. Over the next 12‐hour period he required 4 saline boluses and 2 dextrose boluses due to dry mucous membranes, persistent acidosis and low serum glucose. During that time, he was increasingly difficult to arouse, with generalized hypotonia and brisk DTR’s. Follow up lab evaluation showed correction of hypoglycemia but continued severe acidosis with ketonuria. Ammonia, lactic acid, and LFT’s were unremarkable. The patient’s stool tested positive for rotavirus. After obtaining serum amino acids and urine organic acids, he was started on 10% dextrose containing fluids at high glucose infusion rate (GIR). Within 12 hours of increased GIR, patient’s acidosis began normalizing. Encephalopathy resolved over next few days. Organic acid studies revealed elevated branched chain aminoaciduria consistent with maple syrup urine disease (MSUD). Plasma amino acid levels and genetic testing later confirmed intermittent MSUD. On an appropriate dietary regimen, patient has completely recovered.
Expanded newborn screens (NBS) have had a dramatic impact on early diagnosis and treatment of inborn errors of metabolism (IEM) such as classic MSUD. However, IEM variants may be missed on the NBS. When minor illnesses in these patients lead to metabolic crises, the diagnosis may only be made if the provider has a high index of suspicion. MSUD results from decreased branched chain ketoacid dehydrogenase (BCKD) complex activity with subsequent elevation of leucine, isoleucine and valine, and their corresponding ketoacids. Leucine is neurotoxic and causes cerebral edema. Ketoacids result in the maple syrup smell. Variants of MSUD reflect the spectrum of dysfunction on BCKD complex activity.
In intermittent MSUD, enzyme capacity is overwhelmed during physiologic stress leading to vomiting and lethargy. Left untreated, worsening cerebral edema may result in coma and death. Protein catabolism is suppressed with high GIR (8‐10 mg/kg/min) thereby limiting further leucine accumulation. Rapid intervention prevents further neurologic sequelae and may reverse some deficits. Severe cases may require dialysis to remove the neurotoxic leucine.
Intermittent MSUD is an IEM which may be missed on NBS and can lead to devastating consequences for affected patients. A high index of suspicion for underlying IEM is required when a patient presents with vomiting, lethargy and persistent acidosis. While screening labs and assistance of consultants are necessities, only initiation of 10% dextrose inhibits protein catabolism. Without this intervention, permanent adverse neurologic outcome or death may easily occur.
To cite this abstract:Aggarwal M, Kaperick V. When It Doesn’t Smell Like Rotavirus; Maple Syrup Urine Disease in the 21St Century. Abstract published at Hospital Medicine 2014, March 24-27, Las Vegas, Nev. Abstract 260. Journal of Hospital Medicine. 2014; 9 (suppl 2). https://www.shmabstracts.com/abstract/when-it-doesnt-smell-like-rotavirus-maple-syrup-urine-disease-in-the-21st-century/. Accessed April 1, 2020.