P097: Challenges in newborn screening for mucopolysaccharidosis Type I: A case study

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.