Obesity, Diabetic Ketoacidosis (DKA), Malignant Hyperthermia (MH), and Rhabdomyolysis (RM): A New Phenotype of Carnitine Palmitoyl Transferase Type II (CPTII) Deficiency? J. DiPaola, P.H. Schwartz, N. Anas, T.J. Butler, J. Cappon, S.A. Stein. Crit Care, Neurol and Brain and Tissue Bank, Child Hosp Orange County , Orange, CA.

   Two, unrelated, obese, 15-year-old hispanic boys presented with a clinical picture of new onset DKA after a 1 - 2 week history of fatigue, malaise, polydipsia and polyuria. The clinical course of both patients was catastrophic and led to cardiac arrest. One (A) was successfully resuscitated. The other (B) died in multisystem organ failure. The laboratory values for both were also very similar. Glucose levels at presentation were 1400 mg/dL (A) and 1900 mg/dL (B). Severe metabolic acidosis was noted. Creatine phosphokinase levels reached 47,000 U/L (A) and 68,000 U/L (B). The Mb isoenzyme was elevated but the enzyme/isoenzyme ratios were normal. Both patients had abnormal EKGs, most likely related to electrolyte disturbances. They required endotracheal intubation and high doses of inotropes for cardiovascular support. Both patients had myoglobinuria and developed severe renal failure that required hemodialysis. They also developed MH, measured rectally at 42.8 C (A) and 42.6 C (B), successfully treated with dantrolene. Muscle biopsy of A showed non-specific diffuse myofiber degeneration and regeneration typical of RM; enzymatic testing showed 10% residual CPTII activity which was negative for the S113L mutation. Autopsy of B revealed multisystem organ failure, severe hemorrhagic pancreatitis, and fatty metamorphosis of the liver with hepatomegaly and cirrhosis. The association of DKA and RM, particularly in adults, is well known. There have also been reports of MH in association with diabetes. While RM has been reported in CPTII deficiency, it is usually associated with strenuous exercise or starvation. To our knowledge there has been only one other recognized case similar to those presented here. These cases raise the possibility that CPTII deficiency is the underlying cause for the entire clinical picture and that appropriate preventive measures to avoid MH and a shift to fat metabolism should be taken in addition to measures to control DKA.