P096: A woman with blistering skin and abnormal CBC findings with a novel mutation resulting in aberrant splice of PPOX transcript

Pathogenic variants have been described in several ETF genes, as well as other genes encoding accessory proteins in the pathway.The mainstay of therapy includes avoidance of fasting, a low-fat diet, high-dose riboflavin/carnitine and possibly CoQ10 supplementation.Of note, riboflavin therapy is most beneficial in type 3 MADD.Case Presentation: We describe a 7 year-old female evaluated by Clinical Genomics for a 6 month history of recurrent episodes of altered mental status with hypoglycemic metabolic acidosis and mild hyperammonemia in the setting of emesis.Her past medical history is significant for craniopharyngioma s/p partial resection and radiation therapy at age 4 with subsequent adrenal insufficiency, hypothyroidism and growth hormone deficiency.Diagnostic Workup: Biochemical evaluation included plasma amino acids, plasma acylcarnitine profile and urine organic acids.Urine organic acids revealed elevation of ethylmalonic acid, glutaric acid, 2-hydroxyglutaric acid and methylsuccinic acid.Additionally, isobutyrylglycine, hexanoylglycine and suberylglycine were elevated, which taken together suggested a biochemical MADD phenotype.Molecular testing was pursued with no variants reported in a targeted gene panel including ETFA, ETFB, ETFDH, FLAD1, SLC52A1, SLC52A2, SLC52A3 and TANGO2 genes.Genome sequencing was also negative.