Table S1. Disease classification and disease-reaction association Disorder class Associated reactions cross Disease Ref[Goh check et al., ICD-9-CM Final (KEGG) (BiGG) 2007] & ICD-10- CM Metaboli Metaboli Metaboli R04853|R03783|R02211|R0 P45017A3r|P45017A1r|P450 17,20-lyase deficiency, isolated, 202110 (3) c c c 4852 17A2r|P45017A4r

R04743|R04745|R04748|R0 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency, Metaboli Metaboli Metaboli 4737|R04739|R04741|R019 HACD9m|HACD1m 300438 (3) c c c 75|R04203|R05066|R06941

Metaboli Metaboli Metaboli ACOAD10m|PPCOAOm|A 2-methylbutyrylglycinuria, 610006 (3) c c c COAD1fm Metaboli Metaboli Metaboli 3-Methylcrotonyl-CoA carboxylase 1 deficiency, 210200 (3) R04138 MCCCrm c c c R02840|R04849|R03327|R0 Non- 3328|R02217|R04163|R041 3-beta-hydroxysteroid dehydrogenase, type II, deficiency Metaboli Metaboli HSD3B3r|HSD3B2r|HSD3B13r metaboli 64|R02842|R04851|R02499 (3) c c |HSD3B12r|HSD3B11r c |R02500|R01837|R01839|R 04678|R04680

R04743|R04745|R04748|R0 Metaboli Metaboli Metaboli 3-hydroxyacyl-CoA dehydrogenase deficiency, 231530 (3) 4737|R04739|R04741|R019 HACD1m c c c 75|R04203|R05066|R06941

Metaboli Metaboli Metaboli 3-hydroxyisobutryl-CoA hydrolase deficiency, 250620 (3) 3HPCOAHYD c c c ECOAH1m|T2M26DCOAHL Metaboli Metaboli Metaboli 3-methylglutaconic aciduria, type I, 250950 (3) R02085 m|MGCHrm|PRPNCOAHY c c c Dm|C2M26DCOAHLm Metaboli Metaboli Metaboli AGAT deficiency (3) R01989|R00565 GLYAMDTRc c c c Metaboli Metaboli Metaboli AICA-ribosiduria due to ATIC deficiency, 608688 (3) R04560|R01127 AICART|IMPC c c c Metaboli Metaboli Metaboli Acatalasemia (3) R02670|R00602 CAT2p|CATm|CATp c c c

1

FAOXC140|FAOXC180|FA OXC150m|FAOXC170m|FA OXC2252053m|FAOXC204| ACOAD9m|ACOAD10m|F AOXC1811602m|FAOXC160 80m|FAOXC1811603m|FA OXC16180m|FAOXC204184 R01175|R04751|R03777|R0 m|FAOXC11|FAOXC80|FA 4754|R03857|R03990|R012 OXC182806m|FAOXC18116 Acyl-CoA dehydrogenase, long chain, deficiency of, Metaboli Metaboli Metaboli 79|R04095|R02660|R03170 01m|FAOXC160|FAOXC18 201460 (3) c c c |R02661|R03172|R00924|R 280m|FAOXC200180m|FA 04432|R01171 OXC161802m|FAOXC20518 43m|FAOXC18480m|FAOX C226205m|PPCOAOm|FA OXC2031836m|FAOXC2242 046m|ACOAD1fm|FAOXC 183803m|FAOXC226|FAOX C183806m|FAOXC2251836 m Metaboli Metaboli Metaboli Adenosine deaminase deficiency, partial, 102700 (3) R02556|R01560 DADA|DADAe|ADAe|ADA c c c Metaboli Metaboli Metaboli Adenylosuccinase deficiency, 103050 (3) R04559|R01083 ADSL2|ADSL1 c c c R02383|R04884|R03674|R0 TYRDOPO|T4HCINNOX|TYR Metaboli Metaboli Metaboli Albinism, brown oculocutaneous, (3) 2078|R00731|R02363|R029 DOPO3|DOPACHRMISO|TY c c c 50|R04693 RASE R00710|R00711|R02957|R0 LCADim|GLACOm|5HOXIN 0631|R04506|R02549|R019 DACTOXm|GCALDDm|IMA Non- Metaboli Metaboli 86|R03869|R03283|R04065 CTD_m|ALDD2xm|NABTNO Alcohol intolerance, acute (3) metaboli c c |R02678|R04903|R00904|R m|LCADi_Dm|ALDD20xm| c 01752|R02940|R05119|R06 BAMPPALDOXm|PYLALDOX 366 m Metaboli Metaboli Metaboli Aldolase A deficiency (3) R01070|R02568|R01829 FBA4|FBA2|FBA c c c Metaboli Metaboli Metaboli Alkaptonuria, 203500 (3) R02519 HGNTOR c c c Metaboli Metaboli Metaboli Alpha-methylacetoacetic aciduria, 203750 (3) R01177|R00238 ACACT10m|ACACT1rm c c c Metaboli Metaboli Metaboli AMACR2r|AMACRr|AMAC Alpha-methylacyl-CoA racemase deficiency (3) c c c R2p|AMACRp Metaboli Metaboli Metaboli Aminoacylase 1 deficiency, 609924 (3) R00669 ACODA c c c Metaboli Metaboli Metaboli Argininemia, 207800 (3) R00551|R01086 ARGN|ARGSL c c c 2

R04121|R05259|R03629|R0 7052|R07051|R07050|R070 48|R07042|R07043|R07054 |R07046|R07044|R07045|R Non- 07055|R07056|R07085|R07 Metaboli Metaboli Aromatase deficiency (3) metaboli 087|R07079|R07080|R0708 P45019A2r|P45019A1r c c c 1|R07022|R07021|R07016| R07020|R07000|R07001|R0 7107|R07075|R07098|R070 99|R07066|R07068|R07088 |R07089|R07090|R07112

R01167|R02080|R00736|R0 HISDC|5HLTDL|5HXKYNDCL Aromatic L-amino acid decarboxylase deficiency, 608643 Metaboli Metaboli Metaboli 0699|R04909|R02701|R006 |3HLYTCL|3HXKYNDCL|PHY (3) c c c 85 CBOXL|TYRCBOX|LTDCL Metaboli Metaboli Metaboli GASNASE2ly|GASNASEly|G Aspartylglucosaminuria (3) c c c ASNASE3ly Metaboli Metaboli Metaboli Beta-ureidopropionase deficiency (3) R00905|R04666 UPPN|BUP2 c c c Metaboli Metaboli Metaboli BTNDm|BTND1|BTNDe|BTN Biotinidase deficiency, 253260 (3) R01077 c c c D1n Metaboli Metaboli Metaboli C4STMO2Pr|C3STDH1r|C3S CHILD syndrome, 308050 (3) c c c TDH1Pr|C4STMO2r

3

TETPENT6CPT1|LNELDCCPT1 |TTDCPT2|TMNDNCCPT1|L NLCCPT2|HEXCCPT2|HPDC ACRNCPT2|NRVNCCPT1|A DRNCPT2|ADRNCPT1|VAC CCPT2|LGNCCPT2|LNLNC GCPT2|C180CPT2|C160CP T2|ARACHCPT1|TETTET6CPT 1|VACCCPT1|C161CPT22| CLPNDCPT2|C226CPT1|AR ACHCPT2|EICOSTETCPT2|EI COSTETCPT1|LNLNCGCPT1 |C161CPT1|HEXCCPT1|C1 81CPT1|DLNLCGCPT1|LNL CCPT1|C180CPT1|TETPENT3 CPT2|PTDCACRNCPT2|C16 Metaboli Metaboli Metaboli 0CPT1|STRDNCCPT2|TETPE CPT II deficiency, lethal neonatal, 608836 (3) R01923 c c c NT6CPT2|TETTET6CPT2|ELAI DCPT2|RTOTAL2CRNCPT1| DLNLCGCPT2|RTOTALCRNC PT2|LGNCCPT1|LNELDCCP T2|C161CPT2|DCSPTN1CPT 1|CLPNDCPT1|C204CPT1| DCSPTN1CPT2|TETPENT3CPT 1|NRVNCCPT2|LNLNCACPT 2|RTOTALCRNCPT1|RTOTAL 3CRNCPT2|RTOTAL2CRNCP T2|PTDCACRNCPT1|RTOTA L3CRNCPT1|C181CPT2|C16 1CPT12|C204CPT2|C226CP T2|STRDNCCPT1|TTDCPT1| HPDCACRNCPT1|TMNDNC CPT2|ELAIDCPT1|LNLNCAC PT1 Metaboli Metaboli Metaboli Canavan disease, 271900 (3) R00488|R00526 NACASPAH c c c Metaboli Metaboli Metaboli Carbamoylphosphate synthetase I deficiency, 237300 (3) R00149 CBPSam c c c Carbohydrate-deficient glycoprotein syndrome, type I, Metaboli Metaboli Metaboli R01819|R01818|R05985 M16NTg|PMANM|MAN6PI 212065 (3) c c c Metaboli Metaboli Metaboli METt4|CHOLtu|CRNt|LYSt4 Carnitine deficiency, systemic primary, 212140 (3) c c c |CRNtuNa

4

STRDNCCRNt|DLNLCGCRNt |ACRNtm|ADRNCRNt|LNL NCACRNt|CLPNDCRNt|C1 80CRNt|ELAIDCRNt|ARAC HCRNt|NRVNCCRNt|VACC CRNt|PTDCACRNt|C161CR Nt|LNLCCRNt|RTOTAL3CRN Metaboli Metaboli Metaboli t|C160CRNt|CRNtim|TETPE Carnitine-acylcarnitine translocase deficiency (3) c c c NT3CRNt|LNELDCCRNt|C1 61CRN2t|EICOSTETCRNt|TT DCRNt|LNLNCGCRNt|TETTE T6CRNt|LGNCCRNt|HEXCC RNt|RTOTALCRNt|DCSPTN1 CRNt|HPDCACRNt|C181C RNt|TMNDNCCRNt|RTOTAL 2CRNt|TETPENT6CRNt P45027A15m|VITD3Hm|P45 027A16m|P45027A11m|P45 Metaboli Metaboli Metaboli Cerebrotendinous xanthomatosis, 213700 (3) R04806|R04807 027A1m|VITD2Hm|P45027A c c c 12m|P45027A13m|P45027A 14m Non- Metaboli Metaboli Chitotriosidase deficiency (3) metaboli R01206|R02334 CHTNASE c c c Metaboli Metaboli Metaboli ASPGLUm|3SALAASPm|AR Citrullinemia, 215700 (3) R01954 c c c GSS|GLUt2m

R04121|R05259|R03629|R0 7052|R07051|R07050|R070 48|R07042|R07043|R07054 |R07046|R07044|R07045|R Non- 07055|R07056|R07085|R07 Metaboli Metaboli Codeine sensitivity (3) metaboli 087|R07079|R07080|R0708 P4502D6 c c c 1|R07022|R07021|R07016| R07020|R07000|R07001|R0 7107|R07075|R07098|R070 99|R07066|R07068|R07088 |R07089|R07090|R07112

Metaboli Metaboli Metaboli Combined hyperlipidemia, familial, 144250 (3) R01350 LPS|LPS2 c c c

5

DOLPMT1_Uer|G14T20g|G1 4T18g|G13MT_L|G14T13g| G14T7g|DOLPMT3_Uer|G14 T21g|G14T15g|G14T4g|DO LPGT1_Ler|G14T5g|DOLPM T3_Ler|G14T10g|DOLPGT2_ Uer|G14T16g|G14T14g|G1 Metaboli Metaboli Metaboli R00503|R05972|R05973|R0 4T8g|G13MT_U|BDMT_L|G Congenital disorder of glycosylation, type IIc, 266265 (3) c c c 5989|R01009|R05969 14T19g|GDPFUCtg|GLCNA CPT_L|DOLPMT_L|G14T9g| BDMT_U|DOLPGT2_Ler|G14 T2g|DOLPMT_U|DOLPGT1_ Uer|GLCNACPT_U|G14T11 g|DOLPMT1_Ler|G14T3g|G 14T17g|G14Tg|UGALGTg| G14T12g|G14T6g

R01520|R01521|R02035|R0 Non- Metaboli Metaboli 2834|R02836|R04839|R048 G6PDH2rer|HSD11B1r|PGLe Cortisone reductase deficiency, 604931 (3) metaboli c c 40|R03847|R03848|R04757 r|G6PDH1er|G6PDH1rer c |R04758 Metaboli Metaboli Metaboli Creatine deficiency syndrome, X-linked, 300352 (3) CREATt4(2)r c c c Metaboli Metaboli Metaboli R01001|R00782|R02408|R0 Cystathioninuria, 219500 (3) SELCYSTGL|CYSTGL c c c 4930 Metaboli Metaboli Metaboli AMY1e|CYSTSERex|AMY2e Cystinuria, 220100 (3) c c c |SERLYSNaex C3STKR2r|FAOXC2452256x| FAOXC183806x|FAOXC205 1843x|FAOXC2242046x|PER OXx|FAOXC2252053x|FAO XC2442246x|HACD1x|FAO R04743|R04745|R04748|R0 XC241181x|FAOXC16080x| Metaboli Metaboli Metaboli D-bifunctional protein deficiency, 261515 (3) 4737|R04739|R04741|R019 FAOXC200180x|FAOXC260 c c c 75|R04203|R05066|R06941 240x|FAOXC18480x|FAOX C240200x|HSD17B4x|HSD17 B42x|FAOXC226205x|FAOX C246226x|FAOXC2251836x |FAOXC2452253x|FAOXC1 80x

6

R04121|R05259|R03629|R0 7052|R07051|R07050|R070 48|R07042|R07043|R07054 |R07046|R07044|R07045|R Non- 07055|R07056|R07085|R07 Metaboli Metaboli Debrisoquine sensitivity (3) metaboli 087|R07079|R07080|R0708 P4502D6 c c c 1|R07022|R07021|R07016| R07020|R07000|R07001|R0 7107|R07075|R07098|R070 99|R07066|R07068|R07088 |R07089|R07090|R07112

Non- Metaboli Metaboli DHCR243r|DHCR242r|DHC Desmosterolosis, 602398 (3) metaboli c c R241r c Metaboli Metaboli Metaboli Dihydropyrimidinuria (3) R02269|R03055 DHPM1 c c c Metaboli Metaboli Metaboli Dimethylglycine dehydrogenase deficiency, 605850 (3) R01565 DMGDHm c c c Non- Metaboli Metaboli Dopamine beta-hydroxylase deficiency, 223360 (3) metaboli R02535 DOPABMO c c c Metaboli Metaboli Metaboli Enolase-beta deficiency (3) R00658|R03084 ENO c c c Non- Metaboli Metaboli MCLOR|LDH_L|LDH_Lm|GL Exertional myoglobinuria due to deficiency of LDH-A (3) metaboli R00703|R03104|R01000 c c XO1|HPYRR2x|2HBO c R01101|R03634|R05549|R0 Metaboli Metaboli Metaboli 1103|R01104|R01329|R029 Fabry disease, 301500 (3) GLAl c c c 26|R01194|R04470|R04019 |R05961 Metaboli Metaboli Metaboli MANt1r|GLCt1r|FRUt1r|GA Fanconi-Bickel syndrome, 227810 (3) c c c Lt1r|GAMt1r Non- Metaboli Metaboli Farber lipogranulomatosis (3) metaboli R06518|R06528|R01494 ASAH1 c c c

7

R04743|R04745|R04748|R0 4738|R04740|R04170|R047 ECOAH12m|ECOAH1m|T2 Non- 44|R04746|R04749|R04737 M26DCOAHLm|PRPNCOAH Metaboli Metaboli Fatty liver, acute, of pregnancy (3) metaboli |R04739|R04741|R01975|R YDm|ECOAH9m|HACD1m c c c 03026|R04137|R04204|R04 |ACACT1rm|C2M26DCOA 224|R03045|R05595|R0641 HLm 2|R06411|R06942

Non- Metaboli Metaboli Favism (3) metaboli R02736 G6PDH2r c c c Metaboli Metaboli Metaboli Fish-eye disease, 136120 (3) R02114 LCAT1e c c c Non- Metaboli Metaboli Fluorouracil toxicity, sensitivity to (3) metaboli R00978|R01415 DURAD2|DURAD c c c Metaboli Metaboli Metaboli Fructose intolerance (3) R01070|R02568|R01829 FBA5|FBA4|FBA2|FBA c c c Metaboli Metaboli Metaboli Fructose-bisphosphatase deficiency (3) R04780|R00762 FBP|FBP26 c c c Metaboli Metaboli Metaboli Fructosuria (3) R00866 KHK3|KHK2|KHK c c c Metaboli Metaboli Metaboli Fucosidosis (3) FUCASEly|FUCASE2ly c c c Metaboli Metaboli Metaboli Fumarase deficiency, 606812 (3) R01082 FUMm|FUM c c c Non- Metaboli Metaboli G6PD deficiency (3) metaboli R02736 G6PDH2r c c c Non- Metaboli Metaboli GABA-transaminase deficiency (3) metaboli R01648|R00908|R04188 ABTArm|APAT2rm|3AIBTm c c c Metaboli Metaboli Metaboli GAMT deficiency (3) R01883 GACMTRc c c c

8

NACHEX12ly|GALASE6ly|SI AASE4ly|NACHEX14ly|S6TA SE25ly|NACHEX25ly|NACHE XA11ly|GALASE4ly|NACHE XA21ly|NACHEX3ly|NACHE XA5ly|NACHEX6ly|NACHEX A16ly|GALASE10ly|NACHE XA14ly|NACHEXA19ly|S6TA SE22ly|NACHEX13ly|S6TASE 5ly|NACHEX17ly|GALASE13 ly|NACHEX11ly|NACHEX27l y|SIAASEly|NACHEX22ly|N ACHEXA15ly|NACHEX21ly| NACHEXA13ly|NACHEX8ly| NACHEX2ly|NACHEXA18ly| NACHEXA2ly|NACHEX7ly|N ACHEXA17ly|S6TASE9ly|S6T ASE6ly|GALASE1ly|GALASE 17ly|NACHEXA12ly|GALAS R01678|R04783|R01679|R0 E3ly|LACZly|S6TASE7ly|NA Metaboli Metaboli Metaboli GM1-gangliosidosis (3) 1105|R00022|R03616|R033 CHEX5ly|NACHEXA10ly|SIA c c c 55|R05963|R06010|R06004 ASE3ly|NACHEX16ly|AHEXA SEly|NACHEX4ly|NACHEX1l y|NACHEXA6ly|GALASE11l y|GALASE9ly|GALASE19ly| GALASE20ly|SIAASE2ly|GAL ASE16ly|GALASE7ly|S6TASE 4ly|NACHEX19ly|GLB1|NA CHEX9ly|S6TASE8ly|NACHE XA7ly|GALASE5ly|NACHEX 20ly|NACHEXA20ly|NACHE XA9ly|GALASE12ly|NACHE XA3ly|GALASE15ly|NACHE X24ly|NACHEX23ly|NACHE X26ly|NACHEXA1ly|NACHE XA4ly|NACHEX18ly|NACHE XA8ly|NACHEX10ly|NACHE X15ly|GALASE8ly|AHEXASE 2ly|GALASE18ly|NACHEXA 22ly|GALASE14ly|S6TASE10l y Metaboli Metaboli Metaboli Galactokinase deficiency with cataracts, 230200 (3) R01092 GALK c c c Metaboli Metaboli Metaboli Galactose epimerase deficiency, 230350 (3) R00291|R02984 UDPG4E|UAG4E c c c 9

Metaboli Metaboli Metaboli Galactosemia, 230400 (3) R00955 UGLT|GALT c c c GALASE6ly|SIAASE4ly|S6TA SE25ly|GALASE4ly|GALASE 10ly|S6TASE22ly|S6TASE5ly| GALASE13ly|SIAASEly|S6TA SE9ly|S6TASE6ly|GALASE1ly |GALASE17ly|GALASE3ly|L ACZly|S6TASE7ly|SIAASE3ly Metaboli Metaboli Metaboli Galactosialidosis (3) |GALASE11ly|GALASE9ly| c c c GALASE19ly|GALASE20ly|SI AASE2ly|GALASE16ly|GALA SE7ly|S6TASE4ly|GLB1|S6TA SE8ly|GALASE5ly|GALASE1 2ly|GALASE15ly|GALASE8ly |GALASE18ly|GALASE14ly| S6TASE10ly

Metaboli Metaboli Metaboli R04949|R02887|R00026|R0 Gaucher disease, atypical, 610539 (3) GBA|GBAl c c c 3527|R01498|R04998

Metaboli Metaboli Metaboli MANt1r|GLCt1r|GALt1r|G Glucose transport defect, blood-brain barrier, 606777 (3) c c c AMt1r|DHAAt1r|GLCtg UREAt|GALt2_2|NAt|GLCt Metaboli Metaboli Metaboli Glucose/galactose malabsorption, 606824 (3) 4_2|GLCt2_2|GALt4_2|URE c c c At5|H2Ot Metaboli Metaboli Metaboli Glucosidase I deficiency, 606056 (3) R05979 MG1er c c c Non- Metaboli Metaboli Glutamate formiminotransferase deficiency, 229100 (3) metaboli R02287|R03189|R02302 GluForTx|FTCD c c c Metaboli Metaboli Metaboli R00253|R05030|R05028|R0 Glutamine deficiency, congenital, 610015 (3) GLNS c c c 5033 Metaboli Metaboli Metaboli Glutaricaciduria, type I, 231670 (3) R02487|R02488|R05579 ETFQO|GLUTCOADHm|ETF c c c Non- Metaboli Metaboli Glutathione synthetase deficiency, 266130 (3) metaboli R00497 GTHS c c c L- Metaboli Metaboli Metaboli Glycerol kinase deficiency, 307030 (3) R00847 LACtcm|UREAtm|GLYK|GL c c c YKm GCCam|GNMT|GCC2bim Metaboli Metaboli Metaboli R03425|R00367|R04125|R0 Glycine N-methyltransferase deficiency, 606664 (3) |GCC2cm|GCCcm|GCC c c c 2300|R01221 2am|GCCbim 10

R04779|R01788|R03236|R0 MLTG1ly|G6Pter|GLPASE1| 3237|R03238|R03239|R011 PFK|MALTly|GLPASE2|CBP Metaboli Metaboli Metaboli Glycogen storage disease I (3) 01|R00801|R02111|R00292 Per|GLBRAN|GGNG|PPAe c c c |R02110|R05196|R00802|R r|GLDBRAN|G6PPer|GLGN 00028|R02109 S1 Metaboli Metaboli Metaboli Glycosylphosphatidylinositol deficiency, 610293 (3) GPIMTer_L|GPIMTer_U c c c Non- Gyrate atrophy of choroid and retina with ornithinemia, B6 Metaboli Metaboli metaboli R00667 ORNTArm responsive or unresponsive (3) c c c Non- Metaboli Metaboli HARP syndrome, 607236 (3) metaboli R02971|R04391|R03018 PNTK|PNTKm c c c Metaboli Metaboli Metaboli HDL deficiency, familial, 604091 (3) CHSTEROLt|CHSTEROLtg c c c

R04743|R04745|R04748|R0 4738|R04740|R04170|R047 ECOAH12m|ECOAH1m|T2 Non- 44|R04746|R04749|R04737 M26DCOAHLm|PRPNCOAH Metaboli Metaboli HELLP syndrome, maternal, of pregnancy (3) metaboli |R04739|R04741|R01975|R YDm|ECOAH9m|HACD1m c c c 03026|R04137|R04204|R04 |ACACT1rm|C2M26DCOA 224|R03045|R05595|R0641 HLm 2|R06411|R06942

Metaboli Metaboli Metaboli HMGCOASim|HMGLx|HM HMG-CoA lyase deficiency (3) R01978|R01360 c c c GLm Metaboli Metaboli Metaboli R00190|R01229|R01132|R0 HPRT-related gout, 300323 (3) GUAPRT|HXPRT c c c 2142 Metaboli Metaboli Metaboli Hawkinsinuria, 140350 (3) R02521|R01372 34HPPOR|PPOR c c c Metaboli Metaboli Metaboli Heme oxygenase-1 deficiency (3) R03683 HOXG c c c Metaboli Metaboli Metaboli Hepatic lipase deficiency (3) R02250|R02687 LPS2e|LPS3e|LPSe c c c

11

NACHEX12ly|NACHEX14ly| NACHEX25ly|NACHEXA11ly |NACHEXA21ly|NACHEX3ly |NACHEXA5ly|NACHEX6ly| NACHEXA16ly|NACHEXA14l y|NACHEXA19ly|NACHEX1 3ly|NACHEX17ly|NACHEX1 1ly|NACHEX27ly|NACHEX2 2ly|NACHEXA15ly|NACHEX 21ly|NACHEXA13ly|NACHE X8ly|NACHEX2ly|NACHEXA 18ly|NACHEXA2ly|NACHEX Non- Metaboli Metaboli 7ly|NACHEXA17ly|NACHEX Hex A pseudodeficiency, 272800 (3) metaboli R00022|R05963|R06004 c c A12ly|NACHEX5ly|NACHEX c A10ly|NACHEX16ly|AHEXAS Ely|NACHEX4ly|NACHEX1ly |NACHEXA6ly|NACHEX19ly |NACHEX9ly|NACHEXA7ly| NACHEX20ly|NACHEXA20ly |NACHEXA9ly|NACHEXA3ly |NACHEX24ly|NACHEX23ly |NACHEX26ly|NACHEXA1ly |NACHEXA4ly|NACHEX18ly |NACHEXA8ly|NACHEX10ly |NACHEX15ly|AHEXASE2ly| NACHEXA22ly

Metaboli Metaboli Metaboli Histidinemia, 235800 (3) R01168 HISD c c c Metaboli Metaboli Metaboli BACCLm|BTNPLm|BTNPL|B Holocarboxylase synthetase deficiency, 253270 (3) R05145|R01074 c c c ACCL Metaboli Metaboli Metaboli R01001|R00782|R02408|R0 Homocysteine, total plasma, elevated (3) SELCYSTGL|CYSTGL c c c 4930 Metaboli Metaboli Metaboli R01290|R00891|R04942|R0 Homocystinuria due to MTHFR deficiency, 236250 (3) MTHFR3|SELCYSTS|CYSTS c c c 1224|R01222 Metaboli Metaboli Metaboli Hyper-IgD syndrome, 260920 (3) R02245 MEVK1x c c c Hyperammonemia with hypoornithinemia, LCADim|GCALDDm|GLU5K Metaboli Metaboli Metaboli hypocitrullinemia, hypoargininemia, and hypoprolinemia R03313|R00239 m|LCADi_Dm|AGPRim|G5 c c c (3) SDym Metaboli Metaboli Metaboli Hypercalciuria, absorptive, susceptibility to, 143870 (3) R00089|R00434 ADNCYC c c c

12

R01274|R04828|R03718|R0 Metaboli Metaboli Metaboli BAAT4x|BAAT2x|BAAT3x|B Hypercholanemia, familial, 607748 (3) 3720|R07071|R07072|R070 c c c AAT1x|BAAT5x 82|R07013|R07014|R07027

Non- Metaboli Metaboli Hyperinsulinemic hypoglycemia, familial, 3, 602485 (3) metaboli R01600|R01786 HEX4|HEX1|HEX7|HEX10 c c c

R04743|R04745|R04748|R0 Metaboli Metaboli Metaboli Hyperinsulinemic hypoglycemia, familial, 4, 609975 (3) 4737|R04739|R04741|R019 HACD1m c c c 75|R04203|R05066|R06941

Metaboli Metaboli Metaboli Hyperinsulinism-hyperammonemia syndrome, 606762 (3) R00243|R00248 GLUDym|GLUDxm c c c Metaboli Metaboli Metaboli Hyperlysinemia, 238700 (3) R00715|R00716|R02313 SACCD3m|SACCD4m c c c Hypermethioninemia with deficiency of S- Metaboli Metaboli Metaboli R00177|R00192|R04771|R0 AHC|METAT|SELMETAT|SEA adenosylhomocysteine hydrolase (3) c c c 4936 HCYSHYD

Hyperornithinemia-hyperammonemia-homocitrullinemia Metaboli Metaboli Metaboli ORNt3m|CITRtm|LYStm|AR syndrome, 238970 (3) c c c Gtm|ORNt4m R00369|R00585|R02527|R0 Metaboli Metaboli Metaboli AGTix|SPTix|HPYRRy|LALDD Hyperoxaluria, primary, type 1, 259900 (3) 0717|R01388|R00465|R013 c c c |GLYCLTDy 92 Hyperphenylalaninemia due to pterin-4a-carbinolamine Metaboli Metaboli Metaboli THBPT4ACAMDASE|PHETHPT R01795 dehydratase deficiency, 264070 (3) c c c OX2

LCADim|GLACOm|5HOXIN DACTOXm|GCALDDm|PH R00707|R00708|R05051|R0 CDm|IMACTD_m|HPROxm Metaboli Metaboli Metaboli Hyperprolinemia, type I, 239500 (3) 4444|R04445|R00245|R032 |PROD2m|NABTNOm|4HG c c c 94 LSDm|LCADi_Dm|ALDD20x m|BAMPPALDOXm|P5CDm |PRO1xm|PYLALDOXm Non- R04850|R02843|R03329|R0 Hypoaldosteronism, congenital, due to CMO I deficiency, Metaboli Metaboli metaboli 2218|R03851|R03262|R027 P45011B21m 203400 (3) c c c 25 R01678|R04783|R01679|R0 Metaboli Metaboli Metaboli Hypolactasia, adult type, 223100 (3) 1105|R03616|R03355|R060 LACZe c c c 10 Metaboli Metaboli Metaboli Hypophosphatasia, childhood, 241510 (3) R03024|R04620 ALKP c c c 13

Non- R00720|R00426|R02720|R0 Metaboli Metaboli Inosine triphosphatase deficiency (3) metaboli 1855|R03531|R00662|R021 NTPP11|NTPP9|NTPP10 c c c 00 Metaboli Metaboli Metaboli Isovaleric acidemia, 243500 (3) R04095 ACOAD8m c c c Metaboli Metaboli Metaboli Kanzaki disease, 609242 (3) R05966 NAGAly|NAGA2ly c c c Metaboli Metaboli Metaboli Krabbe disease, 245200 (3) R03617 GALC c c c

R04743|R04745|R04748|R0 4738|R04740|R04170|R047 ECOAH12m|ECOAH1m|T2 44|R04746|R04749|R04737 M26DCOAHLm|PRPNCOAH Metaboli Metaboli Metaboli LCHAD deficiency (3) |R04739|R04741|R01975|R YDm|ECOAH9m|HACD1m c c c 03026|R04137|R04204|R04 |ACACT1rm|C2M26DCOA 224|R03045|R05595|R0641 HLm 2|R06411|R06942

Metaboli Metaboli Metaboli MCLOR|LDH_L|GLXO1|HP Lactate dehydrogenase-B deficiency (3) R00703|R03104|R01000 c c c YRR2x|2HBO Metaboli Metaboli Metaboli Lathosterolosis, 607330 (3) R03310 LSTO1r|LSTO2r c c c Non- Metaboli Metaboli Lead poisoning, susceptibility to (3) metaboli R00036 PPBNGS c c c OIVD3m|GCCam|GCC2bi m|GCC2cm|AKGDm|OIV R00014|R03270|R01698|R0 Leigh syndrome due to cytochrome c oxidase deficiency, Metaboli Metaboli Metaboli D2m|OIVD1m|GCCcm|2 2164|R02166|R00209|R002 256000 (3) c c c OXOADOXm|PDHm|GCC2 10|R03815 am|GCCbim|SUCD1m|NA DH2-u10m Metaboli Metaboli Metaboli R00190|R01229|R01132|R0 Lesch-Nyhan syndrome, 300322, (3) GUAPRT|HXPRT c c c 2142 Metaboli Metaboli Metaboli Lipodystrophy, congenital generalized, type 1, 608594 (3) R02241|R04361 AGPAT1 c c c Metaboli Metaboli Metaboli Lipoprotein lipase deficiency, 238600 (3) R01350 LPS|LPS2 c c c Metaboli Metaboli Metaboli Lowe syndrome, 309000 (3) R04404 PI45P5P c c c Metaboli Metaboli Metaboli Lysinuric protein intolerance, 222700 (3) SERLYSNaex c c c Metaboli Metaboli Metaboli MCDm|MMCD|MMCDp| Malonyl-CoA decarboxylase deficiency, 248360 (3) R00233 c c c MCDp|MMCDm|MCD

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Metaboli Metaboli Metaboli Mannosidosis, alpha-, types I and II, 248500 (3) B_MANNASEly|A_MANASEly c c c OIVD3m|GCCam|GCC2bi R01698|R00209|R00210|R0 m|GCC2cm|AKGDm|OIV Metaboli Metaboli Metaboli Maple syrup urine disease, type II, 248600 (3) 3815|R04225|R01701|R017 D2m|OIVD1m|GCCcm|2 c c c 02 OXOADOXm|PDHm|GCC2 am|GCCbim Metaboli Metaboli Metaboli S4TASE5ly|S4TASE3ly|S4TASE Maroteaux-Lamy syndrome, several forms (3) c c c 2ly|S4TASE4ly|S4TASE1ly Metaboli Metaboli Metaboli McArdle disease, 232600 (3) R02111 GLPASE1|GLPASE2 c c c Non- Metaboli Metaboli MELATNOX|P4502C92|P450 Mephenytoin poor metabolizer (3) metaboli R02468|R02470|R06119 c c 2C94|P4502C93|P4502C19 c Metachromatic leukodystrophy due to deficiency of SAP-1, Metaboli Metaboli Metaboli R04856 ARSA 249900 (3) c c c

Methionine adenosyltransferase deficiency, autosomal Metaboli Metaboli Metaboli R00177|R04771 METAT|SELMETAT recessive (3) c c c Non- Metaboli Metaboli Methylcobalamin deficiency, cblG type, 250940 (3) metaboli R00946 METS c c c LCADim|GCALDDm|LCADi Methylmalonate semialdehyde dehydrogenase deficiency Metaboli Metaboli Metaboli R00705|R00935 _Dm|MMSAD3m|MMSAD1 (3) c c c m Non- Methylmalonic aciduria and homocystinuria, cblC type, Metaboli Metaboli metaboli R00833|R05220 CBL2tm|CBLATm|MMMm 277400 (3) c c c Metaboli Metaboli Metaboli Mevalonicaciduria (3) R02245 MEVK1x c c c Metaboli Metaboli Metaboli Micochondrial phosphate carrier deficiency, 610773 (3) PIt2m c c c

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DNDPt35m|DNDPt61m|DN DPt37m|DNDPt18m|DNDPt 21m|DNDPt31m|DNDPt40 m|DNDPt8m|DNDPt33m|D NDPt42m|DNDPt29m|DND Pt17m|DNDPt27m|DNDPt4 6m|DNDPt52m|DNDPt57m |DNDPt56m|DNDPt41m|D NDPt50m|DNDPt14m|DND Pt47m|DNDPt53m|DNDPt4 m|DNDPt60m|DNDPt12m| DNDPt2m|DNDPt6m|DNDP t10m|DNDPt15m|DNDPt13 Metaboli Metaboli Metaboli m|DNDPt44m|DNDPt9m|D Microcephaly, Amish type, 607196 (3) c c c NDPt28m|DNDPt45m|DND Pt58m|DNDPt62m|DNDPt3 6m|DNDPt23m|DNDPt26m |DNDPt48m|DNDPt43m|D NDPt63m|DNDPt7m|DNDPt 32m|DNDPt20m|DNDPt38 m|DNDPt30m|DNDPt25m| DNDPt55m|DNDPt49m|DN DPt11m|DNDPt34m|DNDPt 16m|DNDPt51m|DNDPt19 m|DNDPt54m|DNDPt59m| DNDPt24m|DNDPt22m|DN DPt1m|DNDPt5m|DNDPt3 m|DNDPt39m

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S6TASE26ly|S6TASE12ly|S6T ASE18ly|GLCAASE4ly|GLC AASE6ly|GALASE6ly|S6TASE 23ly|SIAASE4ly|S6TASE25ly| S6TASE21ly|S2TASE1ly|S6TAS E16ly|GALASE4ly|IDOAASE 2ly|GLCAASE5ly|GALASE10 ly|S6TASE22ly|S6TASE11ly|S 6TASE5ly|GALASE13ly|S6TA SE17ly|SIAASEly|S6TASE2ly| S6TASE20ly|S6TASE13ly|S6T ASE3ly|S6TASE9ly|S6TASE6ly |GALASE1ly|GALASE17ly|S R01478|R01678|R04783|R0 6TASE1ly|GALASE3ly|LACZl Metaboli Metaboli Metaboli Mucopolysaccharidosis II (3) 1679|R01105|R03616|R033 y|S6TASE7ly|SIAASE3ly|GL c c c 55|R06010|R04979 CAASE1ly|IDOAASE1ly|S6T ASE24ly|S2TASE2ly|S6TASE1 9ly|GALASE11ly|GALASE9ly |S2TASE3ly|IDOAASE4ly|G ALASE19ly|GALASE20ly|SIA ASE2ly|GLCAASE9ly|GALAS E16ly|GALASE7ly|S6TASE4ly |S6TASE15ly|GLB1|IDOAAS E3ly|S6TASE8ly|GALASE5ly| GALASE12ly|GALASE15ly|S 6TASE14ly|GLCAASE8ly|GL CAASE7ly|GALASE8ly|GAL ASE18ly|GALASE14ly|S6TAS E10ly

Metaboli Metaboli Metaboli Myoadenylate deaminase deficiency (3) R00181 AMPDA c c c

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TTDCPT2|LNLCCPT2|HEXCC PT2|HPDCACRNCPT2|ADR NCPT2|VACCCPT2|LGNCC PT2|LNLNCGCPT2|C180CPT 2|C160CPT2|C161CPT22|C LPNDCPT2|ARACHCPT2|EI COSTETCPT2|DPGase|TETP ENT3CPT2|PGM|PTDCACR Metaboli Metaboli Metaboli R01516|R01518|R01662|R0 NCPT2|STRDNCCPT2|TETPE Myopathy due to CPT II deficiency, 255110 (3) c c c 1923 NT6CPT2|TETTET6CPT2|ELAI DCPT2|DLNLCGCPT2|RTOT ALCRNCPT2|LNELDCCPT2| C161CPT2|DCSPTN1CPT2|N RVNCCPT2|LNLNCACPT2|R TOTAL3CRNCPT2|RTOTAL2C RNCPT2|C181CPT2|C204C PT2|C226CPT2|DPGM|TMN DNCCPT2 Metaboli Metaboli Metaboli N-acetylglutamate synthase deficiency, 237310 (3) R00259 ACGSm c c c Metaboli Metaboli Metaboli Neuropathy, congenital hypomyelinating, 1, 605253 (3) R03654|R01281 SERPT c c c Metaboli Metaboli Metaboli Norum disease, 245900 (3) R02114 LCAT1e c c c Metaboli Metaboli Metaboli Odontohypophosphatasia, 146300 (3) R03024|R04620 ALKP c c c Non- Metaboli Metaboli MELATNOX|P4502C92|P450 Opremazole poor metabolizer (3) metaboli R02468|R02470|R06119 c c 2C94|P4502C93|P4502C19 c Metaboli Metaboli Metaboli Ornithine transcarbamylase deficiency, 311250 (3) R01398 OCBTm c c c Metaboli Metaboli Metaboli Oroticaciduria (3) R01870|R00965 ORPT|OMPDC c c c FAOXC2452256x|FAOXC18 3806x|FAOXC2051843x|FA OXC2242046x|FAOXC22520 53x|FAOXC2442246x|FAOX R01175|R04751|R03777|R0 C241181x|FAOXC16080x|F Metaboli Metaboli Metaboli Peroxisomal acyl-CoA oxidase deficiency, 264470 (3) 4754|R03857|R03990|R012 AOXC200180x|FAOXC2602 c c c 79 40x|FAOXC18480x|FAOXC 240200x|FAOXC226205x|FA OXC246226x|FAOXC225183 6x|FAOXC2452253x|FAOX C180x|ACOAO7p 18

Metaboli Metaboli Metaboli R01795|R01793|R01794|R0 DHPR|PTHPSn|PTHPS|PHET Phenylketonuria (3) c c c 4286 HPTOX2 Metaboli Metaboli Metaboli Phosphoglycerate dehydrogenase deficiency, 601815 (3) R01512|R01513 PGCD|PGK c c c Metaboli Metaboli Metaboli Phosphoribosyl pyrophosphate synthetase-related gout (3) R01049|R01071 PRPPS c c c Metaboli Metaboli Metaboli Phosphoserine aminotransferase deficiency, 610992 (3) R04173|R05085 PSERT c c c Metaboli Metaboli Metaboli STS1r|STS2r|STS3|STS4r|STS4 Placental steroid sulfatase deficiency (3) R03404 c c c |STS2|STS1|STS3r

Metaboli Metaboli Metaboli R03222|R00084|R03197|R0 UPP3S|UPPDC1|PPBNGS|H Porphyria cutanea tarda (3) c c c 4972|R00036|R03165 MBS|PPPGOm Non- Metaboli Metaboli MELATNOX|P4502C92|P450 Proguanil poor metabolizer (3) metaboli R02468|R02470|R06119 c c 2C94|P4502C93|P4502C19 c Metaboli Metaboli Metaboli Propionicacidemia, 606054 (3) R01859 PPCOACm c c c Metaboli Metaboli Metaboli Protoporphyria, erythropoietic (3) R00310 FCLTm c c c

R00014|R03270|R00200|R0 Metaboli Metaboli Metaboli Pyruvate carboxylase deficiency, 266150 (3) 0344|R00430|R01858|R011 PCm|PDHm|PYK c c c 38|R00209|R00210|R02320

Metaboli Metaboli Metaboli Ribose 5-phosphate isomerase deficiency, 608611 (3) R01056 RPI c c c Metaboli Metaboli Metaboli GLCURtly|ACNAMlt|IDOUR Salla disease, 604369 (3) c c c tly

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NACHEX12ly|NACHEX14ly| NACHEX25ly|NACHEXA11ly |NACHEXA21ly|NACHEX3ly |NACHEXA5ly|NACHEX6ly| NACHEXA16ly|NACHEXA14l y|NACHEXA19ly|NACHEX1 3ly|NACHEX17ly|NACHEX1 1ly|NACHEX27ly|NACHEX2 2ly|NACHEXA15ly|NACHEX 21ly|NACHEXA13ly|NACHE X8ly|NACHEX2ly|NACHEXA 18ly|NACHEXA2ly|NACHEX Sandhoff disease, infantile, juvenile, and adult forms, Metaboli Metaboli Metaboli 7ly|NACHEXA17ly|NACHEX R00022|R05963|R06004 268800 (3) c c c A12ly|NACHEX5ly|NACHEX A10ly|NACHEX16ly|AHEXAS Ely|NACHEX4ly|NACHEX1ly |NACHEXA6ly|NACHEX19ly |NACHEX9ly|NACHEXA7ly| NACHEX20ly|NACHEXA20ly |NACHEXA9ly|NACHEXA3ly |NACHEX24ly|NACHEX23ly |NACHEX26ly|NACHEXA1ly |NACHEXA4ly|NACHEX18ly |NACHEXA8ly|NACHEX10ly |NACHEX15ly|AHEXASE2ly| NACHEXA22ly

GLCNACASE1ly|HS1ly|GLC Metaboli Metaboli Metaboli NACASE5ly|HS3ly|GLCNAC Sanfilippo syndrome, type A, 252900 (3) c c c ASE2ly|GLCNACASE4ly|HS4 ly|GLCNACASE3ly|HS2ly Metaboli Metaboli Metaboli Schindler disease, type I, 609241 (3) R05966 NAGAly|NAGA2ly c c c Non- Metaboli Metaboli Sepiapterin reductase deficiency (3) metaboli R04285|R01813 SPRn|SPR c c c

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GALASE6ly|SIAASE4ly|S6TA SE25ly|GALASE4ly|GALASE 10ly|S6TASE22ly|S6TASE5ly| GALASE13ly|SIAASEly|S6TA SE9ly|S6TASE6ly|GALASE1ly |GALASE17ly|GALASE3ly|L ACZly|S6TASE7ly|SIAASE3ly Metaboli Metaboli Metaboli |GALASE11ly|GALASE9ly| Sialic acid storage disorder, infantile, 269920 (3) R04018 c c c GALASE19ly|GALASE20ly|SI AASE2ly|GALASE16ly|GALA SE7ly|S6TASE4ly|GLCURtly| ACNAMlt|GLB1|S6TASE8ly| GALASE5ly|GALASE12ly|G ALASE15ly|IDOURtly|GALAS E8ly|GALASE18ly|GALASE1 4ly|S6TASE10ly Metaboli Metaboli Metaboli Sialuria, 269921 (3) R02705|R00420|R00414 UAG2EMAi|AMANK c c c R00710|R00711|R02957|R0 NABTNO|GCALDD|PYLALD 0631|R04506|R02549|R019 Non- OX|LCADi|ALDD20x|IMAC Metaboli Metaboli 86|R03869|R03283|R04065 Sjogren-Larsson syndrome, 270200 (3) metaboli TD|ALDD2x|LCADi_D|GLA c c |R02678|R04903|R00904|R c CO|BAMPPALDOX|ALDD2y 01752|R02940|R05119|R06 |ALDD21|5HOXINDACTOX 366 Non- Metaboli Metaboli Statins, attenuated cholesterol lowering by (3) metaboli R02082 HMGCOARr|HMGCOARx c c c Non- Succinic semialdehyde dehydrogenase deficiency, 271980 Metaboli Metaboli LCADim|GCALDDm|SSALx metaboli R00713 (3) c c m|LCADi_Dm c Succinyl CoA:3-oxoacid CoA transferase deficiency, Metaboli Metaboli Metaboli R00410 OCOAT1m 245050 (3) c c c Metaboli Metaboli Metaboli Sucrase-isomaltase deficiency, congenital, 222900 (3) R01791|R01718|R00802 SUCRe|O16G1e|O16G2e c c c Metaboli Metaboli Metaboli Sulfite oxidase deficiency, 272300 (3) R00533 SULFOX c c c Metaboli Metaboli Metaboli Tangier disease, 205400 (3) CHSTEROLt|CHSTEROLtg c c c

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NACHEX12ly|NACHEX14ly| NACHEX25ly|NACHEXA11ly |NACHEXA21ly|NACHEX3ly |NACHEXA5ly|NACHEX6ly| NACHEXA16ly|NACHEXA14l y|NACHEXA19ly|NACHEX1 3ly|NACHEX17ly|NACHEX1 1ly|NACHEX27ly|NACHEX2 2ly|NACHEXA15ly|NACHEX 21ly|NACHEXA13ly|NACHE X8ly|NACHEX2ly|NACHEXA 18ly|NACHEXA2ly|NACHEX Metaboli Metaboli Metaboli 7ly|NACHEXA17ly|NACHEX Tay-Sachs disease, 272800 (3) R00022|R05963|R06004 c c c A12ly|NACHEX5ly|NACHEX A10ly|NACHEX16ly|AHEXAS Ely|NACHEX4ly|NACHEX1ly |NACHEXA6ly|NACHEX19ly |NACHEX9ly|NACHEXA7ly| NACHEX20ly|NACHEXA20ly |NACHEXA9ly|NACHEXA3ly |NACHEX24ly|NACHEX23ly |NACHEX26ly|NACHEXA1ly |NACHEXA4ly|NACHEX18ly |NACHEXA8ly|NACHEX10ly |NACHEX15ly|AHEXASE2ly| NACHEXA22ly

Metaboli Metaboli Metaboli Thymine-uraciluria (3) R00978|R01415 DURAD2|DURAD c c c Metaboli Metaboli Metaboli Transaldolase deficiency, 606003 (3) TALA c c c

R03991|R03858|R04742|R0 3778|R04747|R01177|R047 43|R04745|R04748|R04738 |R04740|R04170|R04744|R ECOAH12m|ECOAH1m|T2 04746|R04749|R04737|R04 M26DCOAHLm|PRPNCOAH Metaboli Metaboli Metaboli Trifunctional protein deficiency, type 1 (3) 739|R04741|R00238|R0197 YDm|ECOAH9m|HACD1m c c c 5|R03026|R04811|R03719| |ACACT1rm|C2M26DCOA R04546|R00927|R04137|R0 HLm 4204|R04224|R00829|R030 45|R05595|R06412|R06411 |R06942

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Metaboli Metaboli Metaboli Tumoral calcinosis, hyperphosphatemic, familial, 211900 (3) R05907 GALNTg c c c Metaboli Metaboli Metaboli R07396|R02521|R00734|R0 TYRTAm|FUMAC|34HPPOR Tyrosinemia, type I (3) c c c 1364|R01372|R00694 |PPOR|PHETA1m Non- Metaboli Metaboli Urolithiasis, 2,8-dihydroxyadenine (3) metaboli R00190|R01229|R04378 ADPT|PIt7 c c c Non- Metaboli Metaboli Wernicke-Korsakoff syndrome, susceptibility to, 277730 (3) metaboli R01641|R01830|R01067 TKT2|TKT1 c c c Metaboli Metaboli Metaboli R01768|R02103|R02107|R0 Xanthinuria, type I, 278300 (3) XAO2x|XAOx|XANDp c c c 1769

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