Molecular Testing for Diseases Targeted By Ontario Using Next Generation Sequencing:

Inborn Errors of , Congenital Adrenal Hyperplasia, Sickle Cell Disease and Severe Combined Immune Deficiencies

AMINO ACID DISORDERS Primary Targets Disease Inheritance Phenylketonuria Autosomal Recessive PAH BCKDHA

Maple Syrup Urine Disease Autosomal Recessive BCKDHB

DBT Tyrosinemia Type 1 Autosomal Recessive FAH Citrullinemia Type 1 Autosomal Recessive ASS1 ASL Argininosuccinic acidemia Autosomal Recessive Homocystinuria Caused by Cystathionine Beta- CBS Autosomal Recessive Synthase Deficiency Secondary Targets Disease Inheritance Gene Arginase Deficiency Autosomal Recessive ARG1 Tyrosinemia Type II Autosomal Recessive TAT Tyrosinemia Type III Autosomal Recessive HPD Hypermethioninemia with S- AHCY Autosomal Recessive / Adenosylhomocysteine Hydrolase Deficiency GNMT Autosomal Dominant MAT1A BH4-Deficient Hyperphenylalaninemia C Autosomal Recessive QDPR

415 Smyth Road Ottawa Ontario K1H 8M8 Toll-free: 1877-NBS-8330 / Local: (613)738-3222 www.newbornscreening.on.ca @NBS_Ontario

ORGANIC ACID DISORDERS Primary Targets Disease Inheritance Gene PCCA Autosomal Recessive PCCB MUT Autosomal Recessive MMAA MMAB Isovaleric Acidemia Autosomal Recessive IVD Holocarboxylase Synthetase Deficiency Autosomal Recessive HLCS MCCC1 3-Methylcrotonyl-CoA Carboxylase Deficiency Autosomal Recessive MCCC2 3-Hydroxy-3-Methylglutaryl-Coenzyme A Lyase Autosomal Recessive HMGCL Deficiency Ketothiolase Deficiency [Beta-Ketothiolase Autosomal Recessive ACAT1 Deficiency] Glutaric Acidemia Type 1 Autosomal Recessive GCDH Secondary Targets Disease Inheritance Gene Cobalamin C Deficiency Autosomal Recessive MMACHC Cobalamin D Deficiency Autosomal Recessive MMADHC 17-Beta-Hydroxysteroid Dehydrogenase X X-Linked HSD17B10 Deficiency 3-Methylglutaconic Aciduria Type I Autosomal Recessive AUH Type II X-Linked TAZ Type III Autosomal Recessive OPA3 Type V Autosomal Recessive DNAJC19 Isobutyryl-CoA Dehydrogenase Deficiency Autosomal Recessive ACAD8 Acyl-CoA Dehydrogenase, Short/Branched Autosomal Recessive ACADSB Chain Deficiency Malonyl-CoA Decarboxylase Deficiency Autosomal Recessive MLYCD

415 Smyth Road Ottawa Ontario K1H 8M8 Toll-free: 1877-NBS-8330 / Local: (613)738-3222 www.newbornscreening.on.ca @NBS_Ontario

FATTY ACID OXIDATION DISORDERS Primary Targets Disease Inheritance Gene Systemic Primary Deficiency Autosomal Recessive SLC22A5 Medium Chain Acyl-Coenzyme A Autosomal Recessive ACADM Dehydrogenase Deficiency Very Long Chain Acyl-Coenzyme A Autosomal Recessive ACADVL Dehydrogenase Deficiency Long Chain 3-Hydroxyacyl-CoA Autosomal Recessive HADHA Dehydrogenase Deficiency HADHA Trifunctional Deficiency Autosomal Recessive HADHB Secondary Targets Disease Inheritance Gene ETFA Multiple Acyl-CoA Dehydrogenase Deficiency Autosomal Recessive ETFB ETFDH Carnitine Palmitoyltransferase IA Deficiency Autosomal Recessive CPT1A Carnitine Palmitoyltransferase II Deficiency Autosomal Recessive CPT2 Carnitine-Acylcarnitine Translocase Deficiency Autosomal Recessive SLC25A20

OTHER DISORDERS Disease Inheritance Gene Galactosemia Autosomal Recessive GALT Deficiency Autosomal Recessive BTD 21-Hydroxylase-Deficient Congenital Adrenal Autosomal Recessive CYP21A2 Hyperplasia Sickle Cell Disease / β-thalassemia Autosomal Recessive HBB

415 Smyth Road Ottawa Ontario K1H 8M8 Toll-free: 1877-NBS-8330 / Local: (613)738-3222 www.newbornscreening.on.ca @NBS_Ontario

SEVERE COMBINED IMMUNE DEFICIENCIES (SCID) Disease Inheritance Gene X-Linked Severe Combined Immune Deficiency X-Linked IL2RG Adenosine Deaminase Deficiency Autosomal Recessive ADA Severe Combined Immune Deficiency, Autosomal Recessive T Cell-Negative, B Cell- Autosomal Recessive IL7R Positive, NK Cell-Positive, IL7R-Related Severe Combined Immune Deficiency, Autosomal Recessive, T Cell-Negative, B Cell- Autosomal Recessive JAK3 Positive, NK Cell-Negative, JAK3-Related Purine Nucleoside Phosphorylase Deficiency Autosomal Recessive PNP

Severe Combined Immune Deficiency, RAG1 Autosomal Recessive, T Cell-Negative, B Cell- Autosomal Recessive Negative, NK Cell-Positive, RAG1/RAG2- Related RAG2 Severe Combined Immune Deficiency, Autosomal Recessive, T Cell-Negative, B Cell- Autosomal Recessive CD3D Positive, NK Cell-Positive, CD3D-Related

Severe Combined Immune Deficiency, Autosomal Recessive, T Cell-Negative, B Cell- Autosomal Recessive CD3E Positive, NK Cell-Positive, CD3E-Related Immune Deficiency due to Defect in CD3-zeta Autosomal Recessive CD247 Omenn Syndrome Autosomal Recessive DCLRE1C Severe Combined Immune Deficiency with Autosomal Recessive AK2 Leukopenia Severe Combined Immune Deficiency with Microcephaly, Growth Retardation, and Autosomal Recessive NHEJ1 Sensitivity to Ionizing Radiation Severe Combined Immune Deficiency with Autosomal Recessive LIG4 Sensitivity to Ionizing Radiation Neutrophil Immune Deficiency Syndrome Autosomal Recessive RAC2 SCID, T cell-negative, B-cell/natural killer-cell Autosomal Recessive PTPRC positive, PTPRC-related ZAP70-Related Severe Combined Immune Autosomal Recessive ZAP70 Deficiency Cartilage-Hair Hypoplasia Autosomal Recessive RMRP Immune Deficiency 26, with or without Autosomal Recessive PRKDC neurologic abnormalities Immune Deficiency-11 Autosomal Recessive CARD11

415 Smyth Road Ottawa Ontario K1H 8M8 Toll-free: 1877-NBS-8330 / Local: (613)738-3222 www.newbornscreening.on.ca @NBS_Ontario