The main hypothesis of this research is that patients that present with recurrent ketoacidosis without diabetes have a defect in MCT-1 or SCOT. These researchers are seeking to identify patients who have recurrent and severe ketoacidosis with normal or low blood glucose levels (non-diabetic). The episodic bouts of ketosis may be provoked by poor feeding (fasting) or infections (vomiting) in their first years of life. Serum ketone (and urine ketone excretion) levels are expected to be clearly elevated. Treatment with intravenous glucose or dextrose (combined with bicarbonate) may lead to rapid clearance of metabolic acidosis. Normal enzymatic activities of ACAT1 (acetoacetyl-CoA thiolase 1) and SCOT (succinyl CoA oxoacid transferase) will have ruled out known ketolytic defects.
The project has three specific aims:
- Characterize MCT-1 mutations in the context of patients that have recurrent ketoacidosis and who do not have diabetes.
- Characterize SCOT mutations in the context of patients that have recurrent ketoacidosis and who do not have diabetes.
- Explore the possibility that MCT-1 is a prototype for other brain barrier transport deficiencies such as the case with ACAT1 and SCOT.