Metabolic Diseases incl. Mitochondriopathies

Analysis of all known genes associated with metabolic diseases incl. mitochondriopathies

GC_1 Monogenic Diabetes

Monogenic diabetes results from pathogenic variants affecting pancreatic β-cell development or function, insulin secretion, insulin signaling, or other pathways involved in glucose homeostasis. Clinical presentations include neonatal diabetes, maturity-onset diabetes of the young (MODY), syndromic diabetes, mitochondrial diabetes, and other inherited forms of non-autoimmune diabetes.

This panel includes genes associated with the major forms of monogenic diabetes, including MODY, neonatal diabetes, insulin resistance syndromes, mitochondrial diabetes, and syndromic forms of diabetes.

This panel is recommended for patients with early-onset, non-autoimmune, familial, or otherwise unexplained diabetes, particularly when the clinical presentation is atypical for type 1 or type 2 diabetes or when a molecular diagnosis may influence treatment, surveillance, or family testing.

Last update: 06.01.2026

ABCC8, AGPAT2, AIRE, AKT2, APPL1, BLK, BSCL2, CEL, CISD2, CNOT1, DCAF17, DNAJC3, DUT, DYRK1B, EIF2AK3, EIF2B1, EIF2S3, FICD, FOXP3, GATA4, GATA6, GCK, GLIS3, GLUD1, HADH, HNF1A, HNF1B, HNF4A, IER3IP1, IL2RA, INS, INSR, KBTBD2, KCNJ11, KLF11, LMNA, LRBA, MNX1, MT-ATP6, MT-ATP8, MT-CO1, MT-CO2, MT-CO3, MT-CYB, MT-ND1, MT-ND2, MT-ND3, MT-ND4, MTND4L, MT-ND5, MT-ND6, MT-RNR1, MT-RNR2, MT-TA, MT-TC, MT-TD, MT-TE, MT-TF, MT-TG, MTTH, MT-TI, MT-TK, MT-TL1, MT-TL2, MT-TM, MT-TN, MT-TP, MT-TQ, MT-TR, MT-TS1, MT-TS2, MT-TT, MT-TV, MT-TW, MT-TY, NEUROD1, NEUROG3, NKX2-2, ONECUT1, PAX4, PAX6, PCBD1, PDIA6, PDX1, PIK3R1, PLIN1, POC5, POLD1, PPARG, PPP1R15B, PTF1A, RFX6, RNU4ATAC, RNU6ATAC, SLC16A1, SLC19A2, SLC29A3, SLC2A2, SMPD4, STAT3, TARS2, TMEM167A, TRMT10A, UCP2, WFS1, YIPF5, ZBTB20, ZFP57, ZMPSTE24, ZNF808

GC_7 Obesity

Monogenic obesity is characterized by severe, often early-onset obesity caused by inherited abnormalities affecting appetite and satiety regulation, energy homeostasis, hypothalamic signaling, or broader developmental pathways. Clinical manifestations may include hyperphagia, developmental delay, endocrine abnormalities, dysmorphic features, and multisystem involvement.

This panel includes genes associated with monogenic obesity, hypothalamic obesity syndromes, ciliopathies, and other syndromic disorders in which obesity is a prominent feature.

This panel is recommended for patients with severe childhood-onset obesity, particularly when associated with marked hyperphagia, developmental abnormalities, endocrine dysfunction, dysmorphic features, or other findings suggestive of a monogenic or syndromic obesity disorder.

Last update: 07.01.2026

ADCY3, AFF4, ALMS1, ARL6, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, BDNF, C8ORF37, CEP164, CEP19, CEP290, CPE, CREBBP, CUL4B, DYRK1B, EP300, FBN3, GNAS, GNB1, GPR101, IFT172, IFT27, IFT74, INPP5E, KDM6A, KIDINS220, KIF7, KMT2D, KSR2, LEP, LEPR, LZTFL1, MAGEL2, MC3R, MC4R, MEGF8, MKKS, MKS1, MRAP2, MYT1L, NLGN2, NPY, NR0B2, NTRK2, PCSK1, PGM2L1, PHF6, PHIP, POMC, PPARG, PRMT7, PTPN4, RAB23, RAI1, RPS6KA3, SCLT1, SDCCAG8, SETD2, SH2B1, SIM1, STX16, TRAPPC3, TRAPPC9, TRIM32, TRPC5, TTC8, TUB, UCP3, VPS13B, WDPCP

ClinVar P/LP variants (IDs) not covered: CEP290:[3774377] | RAI1:[1321231]

GC_9 Glycogen Storage Disease

Glycogen storage diseases (GSDs) are inherited metabolic disorders caused by defects in glycogen synthesis, degradation, or regulation, resulting in abnormal glycogen accumulation or impaired glucose homeostasis. Clinical manifestations vary by subtype and may include fasting hypoglycemia, hepatomegaly, myopathy, cardiomyopathy, exercise intolerance, or multisystem disease.

This panel includes genes associated with the major hepatic, muscle, and multisystem glycogen storage disorders, including glycogen storage disease types I–XV, Pompe disease, Danon disease, and related glycogen metabolism disorders. Representative genes include G6PC1, GAA, PYGL, PYGM, PHKA2, GBE1, GYS2, and LAMP2.

This panel is recommended for patients with clinical features suggestive of a glycogen storage disorder, particularly those with hypoglycemia, hepatomegaly, elevated liver enzymes, exercise intolerance, recurrent rhabdomyolysis, cardiomyopathy, or unexplained hyperCKemia.

Last update: 07.01.2026

AGL, ALDOA, ALDOB, ENO3, EPM2A, FBP1, G6PC1, GAA, GBE1, GYG1, GYS1, GYS2, LAMP2, LDHA, LPIN1, NHLRC1, PCK1, PCK2, PFKM, PGAM2, PGK1, PGM1, PHKA1, PHKA2, PHKB, PHKG2, POLG, PRKAG2, PRKAG3, PYGL, PYGM, RBCK1, SLC2A2, SLC37A4

ClinVar P/LP variants (IDs) not covered: AGL: [4529480]

GC_35 Hypoglycemia and Hyperinsulinisim

Monogenic disorders of glucose homeostasis comprise a heterogeneous group of endocrine and metabolic diseases that may cause recurrent or persistent hypoglycemia, particularly during infancy and childhood. Clinical manifestations may include hyperinsulinism, seizures, lethargy, developmental delay, fasting intolerance, and other metabolic abnormalities.

This panel includes genes associated with congenital hyperinsulinism as well as other inherited causes of hypoglycemia, including glycogen storage diseases, fatty acid oxidation defects, gluconeogenesis disorders, endocrine disorders, and selected metabolic diseases.

This panel is recommended for patients with recurrent, persistent, or severe hypoglycemia, documented or suspected hyperinsulinism, or otherwise unexplained hypoglycemic episodes when an inherited endocrine or metabolic disorder is suspected.

Last update: 19.01.2026

AAAS, ABCC8, ABCD1, ACAD9, ACADM, ACADS, ACADSB, ACADVL, ACAT1, ACSF3, ADK, AGL, AKT2, ALDOA, ALDOB, ALG3, ALG6, BCKDHA, BCKDHB, BTD, CA5A, CACNA1C, CACNA1D, CDKN1C, COG7, CPT1A, CPT2, CYP7B1, DBH, DBT, DDC, DGUOK, DLD, DMXL2, DOLK, ENO3, EPM2A, ETFA, ETFB, ETFDH, FAH, FBP1, FLAD1, FOXA2, G6PC1, GAA, GALE, GALK1, GALT, GBE1, GCK, GH1, GHR, GLUD1, GPC3, GYG1, GYS1, GYS2, HADH, HADHA, HADHB, HESX1, HK1, HLCS, HMGCL, HMGCS2, HNF1A, HNF4A, HRAS, HSD3B7, INSR, IVD, KCNJ11, KDM6A, KMT2A, KMT2D, LAMP2, LDHA, LHX3, MAGEL2, MCEE, MLYCD, MMUT, MPI, MPV17, NADK2, NHLRC1, NNT, NR0B1, NR3C1, NSD1, OPLAH, OTX2, OXCT1, PC, PCCA, PCCB, PCK1, PCK2, PCSK1, PDX1, PFKM, PGAM2, PGK1, PGM1, PHGDH, PHKA1, PHKA2, PHKB, PHKG2, PMM2, POMC, PRKAG2, PRKAG3, PROP1, PTF1A, PYGL, PYGM, RBCK1, SERAC1, SLC16A1, SLC22A5, SLC25A20, SLC25A32, SLC2A2, SLC37A4, SLC52A1, SLC52A2, SLC52A3, SOX2, SOX3, TAFAZZIN, TANGO2, TBX19, TRMT10A, UCP2

ClinVar P/LP variants (IDs) not covered: AGL:[4529480] | GALT:[4541441] | HADHB:[3359235] | SERAC1:[4526663]

GC_41 Inborn errors of Metabolism

Inborn errors of metabolism are a heterogeneous group of genetic disorders affecting biochemical pathways involved in cellular metabolism. These conditions may disrupt amino acid, organic acid, carbohydrate, lipid, lysosomal, peroxisomal, or mitochondrial pathways. Clinical manifestations range from severe neonatal metabolic crises to progressive or episodic multisystem disease presenting in childhood or adulthood.

This comprehensive panel includes genes associated with the major categories of inherited metabolic disease, including amino acid disorders, organic acidemias, urea cycle disorders, fatty acid oxidation disorders, mitochondrial diseases, lysosomal storage disorders, peroxisomal disorders, glycogen storage diseases, and disorders of carbohydrate metabolism.

This panel is recommended for patients with suspected inherited metabolic disease, particularly those with multisystem involvement, unexplained metabolic abnormalities, recurrent metabolic decompensation, or inconclusive biochemical investigations.

Last update: 18.01.2026

AAAS, AARS2, AASS, ABAT, ABCA1, ABCB11, ABCB4, ABCB6, ABCB7, ABCC2, ABCC8, ABCD1, ABCD3, ABCD4, ABCG5, ABCG8, ABHD12, ABHD5, ACACA, ACAD8, ACAD9, ACADL, ACADM, ACADS, ACADSB, ACADVL, ACAT1, ACBD5, ACO2, ACOX1, ACOX2, ACSF3, ACY1, ADA, ADAMTSL2, ADAR, ADK, ADSL, AFG3L2, AGA, AGK, AGL, AGPAT2, AGPS, AGXT, AHCY, AIFM1, AKR1D1, AKT2, ALAD, ALAS2, ALDH18A1, ALDH3A2, ALDH4A1, ALDH5A1, ALDH6A1, ALDH7A1, ALDOA, ALDOB, ALG1, ALG11, ALG12, ALG13, ALG14, ALG2, ALG3, ALG6, ALG8, ALG9, ALPL, AMACR, AMN, AMPD1, AMT, ANO10, ANO5, ANTXR2, AP1B1, AP1S1, APOA1, APOA2, APOA5, APOB, APOC2, APOE, APRT, APTX, ARG1, ARSA, ARSB, ARSG, ARSK, ARSL, ASAH1, ASL, ASPA, ASS1, ATAD3A, ATIC, ATP13A2, ATP2A1, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1E, ATP5MC3, ATP5PO, ATP6AP1, ATP6V0A2, ATP7A, ATP7B, ATP8B1, ATPAF2, AUH, B3GALNT2, B3GALT6, B3GAT3, B3GLCT, B4GALNT1, B4GALT1, B4GALT7, B4GAT1, BAAT, BCAP31, BCAT2, BCKDHA, BCKDHB, BCKDK, BCS1L, BOLA3, BSCL2, BSND, BTD, C10ORF2, C12ORF65, C19orf12, C1QBP, C2orf69, CA5A, CACNA1S, CAPN3, CARS2, CASQ1, CASR, CAT, CAV1, CAV3, CAVIN1, CBLIF, CBS, CCDC115, CD320, CETP, CFTR, CHCHD10, CHKB, CHST14, CHST3, CHST6, CHSY1, CIDEC, CISD2, CLCN1, CLCN7, CLCNKB, CLDN16, CLDN19, CLN3, CLN5, CLN6, CLN8, CLPB, CLPP, CMPK2, CNNM2, CNNM4, COA3, COA6, COA7, COA8, COASY, COG1, COG3, COG4, COG5, COG6, COG7, COG8, COL11A2, COL2A1, COQ2, COQ4, COQ5, COQ6, COQ7, COQ8A, COQ8B, COQ9, COX10, COX11, COX14, COX15, COX18, COX20, COX4I1, COX4I2, COX5A, COX6A1, COX6A2, COX6B1, COX7B, CP, CPOX, CPS1, CPT1A, CPT2, CREB3L3, CRLS1, CRPPA, CSGALNACT1, CSTB, CTDP1, CTH, CTNS, CTSA, CTSC, CTSD, CTSF, CTSK, CUBN, CYB5A, CYB5R3, CYC1, CYCS, CYP11B1, CYP17A1, CYP19A1, CYP21A2, CYP27A1, CYP7B1, D2HGDH, DAG1, DARS1, DARS2, DBH, DBT, DCC, DCXR, DDC, DDOST, DGUOK, DHCR24, DHCR7, DHDDS, DHFR, DHODH, DHRSX, DHTKD1, DIABLO, DLAT, DLD, DLX4, DMD, DNA2, DNAJB6, DNAJC12, DNAJC19, DNAJC5, DNM1L, DNM2, DOLK, DPAGT1, DPM1, DPM2, DPM3, DPYD, DPYS, DYM, DYSF, EARS2, EBP, ECHS1, EDEM3, EGF, EHBP1L1, EHHADH, ELAC2, EMD, ENO3, ENPP1, EOGT, EPG5, EPHX2, EPM2A, ERAL1, ETFA, ETFB, ETFDH, ETHE1, EXT1, EXT2, FA2H, FAH, FAM111A, FAR1, FARS2, FASTKD2, FBP1, FBXL4, FCSK, FDX2, FDXR, FECH, FGF23, FGFR2, FH, FHL1, FKRP, FKTN, FLAD1, FLNA, FLNB, FMO3, FOLR1, FOXRED1, FTCD, FUCA1, FUT8, FXN, FXYD2, G6PC1, G6PC3, G6PD, GAA, GABRG2, GALC, GALE, GALK1, GALM, GALNS, GALNT2, GALNT3, GALT, GAMT, GARS1, GATC, GATM, GBA, GBE1, GCDH, GCGR, GCH1, GCK, GCLC, GCSH, GDAP1, GFER, GFM1, GFM2, GFPT1, GHR, GK, GLA, GLB1, GLDC, GLRA1, GLRX5, GLS, GLUD1, GLUL, GLYCTK, GM2A, GMPPA, GMPPB, GNE, GNMT, GNPAT, GNPTAB, GNPTG, GNS, GORAB, GPC3, GPD1, GPHN, GPIHBP1, GPT2, GRHPR, GRN, GSS, GSTZ1, GTPBP3, GUK1, GUSB, GYG1, GYS1, GYS2, HAAO, HADH, HADHA, HADHB, HAMP, HARS2, HCCS, HCFC1, HEXA, HEXB, HFE, HGD, HGSNAT, HIBCH, HJV, HLCS, HMBS, HMGCL, HMGCS2, HMOX1, HNF1A, HNF1B, HNF4A, HOGA1, HPD, HPDL, HPRT1, HPS1, HRAS, HS2ST1, HSD11B2, HSD17B10, HSD17B4, HSD3B2, HSD3B7, HSPA9, HSPD1, HTRA2, HYAL1, IARS2, IBA57, IDH1, IDH2, IDH3A, IDS, IDUA, IER3IP1, IFIH1, INSR, ISCA1, ISCA2, ISCU, ITPA, IVD, KARS1, KCNA1, KCNJ10, KCNJ11, KCNJ2, KHK, KYNU, L2HGDH, LAMA2, LAMP2, LARGE1, LARS1, LARS2, LBR, LCAT, LCT, LDB3, LDHA, LDHD, LDLR, LDLRAP1, LETM1, LFNG, LIAS, LIG3, LIPA, LIPC, LIPE, LIPT1, LIPT2, LMBRD1, LMF1, LMNA, LONP1, LPA, LPIN1, LPL, LRPPRC, LYRM4, LYRM7, MAGT1, MAN1B1, MAN2B1, MAN2B2, MANBA, MAOA, MARS2, MAT1A, MCCC1, MCCC2, MCEE, MCOLN1, MDH2, MECR, MFF, MFN2, MFSD8, MGAT2, MGME1, MICOS13, MICU1, MIPEP, MLYCD, MMAA, MMAB, MMACHC, MMADHC, MMUT, MOCOS, MOCS1, MOCS2, MOGS, MPC1, MPDU1, MPI, MPV17, MRM2, MRPL3, MRPL39, MRPL44, MRPL49, MRPS14, MRPS16, MRPS2, MRPS22, MRPS34, MRPS7, MSMO1, MSTO1, MT-ATP6, MT-ATP8, MT-CO1, MT-CO2, MT-CO3, MT-CYB, MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L, MT-ND5, MT-ND6, MT-RNR1, MT-RNR2, MT-TA, MT-TC, MT-TD, MT-TE, MT-TF, MT-TG, MT-TH, MT-TI, MT-TK, MT-TL1, MT-TL2, MT-TM, MT-TN, MT-TP, MT-TQ, MT-TR, MT-TS1, MT-TS2, MT-TT, MT-TV, MT-TW, MT-TY, MTFMT, MTHFR, MTO1, MTPAP, MTR, MTRFR, MTRR, MTTP, MVK, MYH3, MYOT, NADK2, NAGA, NAGLU, NAGS, NARS2, NAXD, NAXE, NBAS, NDUFA1, NDUFA10, NDUFA11, NDUFA12, NDUFA13, NDUFA2, NDUFA4, NDUFA6, NDUFA8, NDUFA9, NDUFAF1, NDUFAF2, NDUFAF3, NDUFAF4, NDUFAF5, NDUFAF6, NDUFAF8, NDUFB10, NDUFB11, NDUFB3, NDUFB7, NDUFB8, NDUFB9, NDUFC2, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV2, NEU1, NFS1, NFU1, NGLY1, NHLRC1, NIPA2, NNT, NPC1, NPC2, NR0B1, NSDHL, NSUN3, NT5C3A, NT5E, NUBPL, NUS1, OAT, OCRL, OGDH, OPA1, OPA3, OPLAH, OTC, OXCT1, PAH, PANK2, PARS2, PC, PCBD1, PCCA, PCCB, PCK1, PCSK9, PDE12, PDHA1, PDHB, PDHX, PDK3, PDP1, PDSS1, PDSS2, PDX1, PEPD, PET100, PET117, PEX1, PEX10, PEX11B, PEX12, PEX13, PEX14, PEX16, PEX19, PEX2, PEX26, PEX3, PEX5, PEX6, PEX7, PFKM, PGAM2, PGAP2, PGAP3, PGK1, PGM1, PGM3, PHGDH, PHKA1, PHKA2, PHKB, PHKG2, PHYH, PIGA, PIGL, PIGM, PIGN, PIGO, PIGS, PIGT, PIGV, PIGW, PINK1, PITRM1, PKLR, PLA2G6, PLIN1, PLPBP, PMM2, PMPCA, PMPCB, PNP, PNPLA2, PNPLA8, PNPO, PNPT1, POLG, POLG2, POLRMT, POMGNT1, POMGNT2, POMK, POMT1, POMT2, POR, PPA2, PPARG, PPM1K, PPOX, PPP1R17, PPT1, PRDX1, PRKAG2, PRKAG3, PRODH, PRORP, PRPS1, PSAP, PSAT1, PSPH, PTCD3, PTF1A, PTS, PUS1, PYCR1, PYGL, PYGM, QARS1, QDPR, QRSL1, RAI1, RANBP2, RARS2, RBCK1, RBP4, REN, RFT1, RMND1, RNASEH1, RNASEH2A, RNASEH2B, RNASEH2C, RNASET2, RPIA, RPL10, RRM2B, RTN4IP1, RXYLT1, RYR1, SACS, SAMHD1, SAR1B, SARS2, SC5D, SCN4A, SCO1, SCO2, SCP2, SDHA, SDHAF1, SDHAF2, SDHB, SDHC, SDHD, SEC23B, SERAC1, SERPINA1, SETX, SFXN4, SGCA, SGCB, SGCD, SGCG, SGSH, SHMT2, SI, SIL1, SKIV2L, SLC12A3, SLC13A3, SLC16A1, SLC17A5, SLC18A2, SLC19A2, SLC19A3, SLC22A5, SLC25A1, SLC25A12, SLC25A13, SLC25A15, SLC25A19, SLC25A20, SLC25A22, SLC25A24, SLC25A26, SLC25A3, SLC25A32, SLC25A36, SLC25A38, SLC25A4, SLC25A42, SLC25A46, SLC2A1, SLC2A2, SLC30A10, SLC31A1, SLC35A1, SLC35A2, SLC35C1, SLC35D1, SLC37A4, SLC39A13, SLC39A14, SLC39A4, SLC39A8, SLC3A1, SLC40A1, SLC46A1, SLC52A1, SLC52A2, SLC52A3, SLC5A1, SLC5A6, SLC6A19, SLC6A3, SLC6A8, SLC6A9, SLC7A7, SLC7A9, SLCO1B1, SLCO1B3, SMPD1, SPATA5, SPG7, SPR, SPTLC1, SPTLC2, SQOR, SRD5A3, SSBP1, SSR3, SSR4, ST3GAL3, ST3GAL5, STAC3, STAT2, STS, STT3A, STT3B, SUCLA2, SUCLG1, SUGCT, SUMF1, SUOX, SUPV3L1, SURF1, TACO1, TAFAZZIN, TALDO1, TAMM41, TANGO2, TARS2, TAT, TBC1D4, TCAP, TCF4, TCN2, TEFM, TFAM, TFR2, TH, THAP11, TIMM50, TIMM8A, TIMMDC1, TK2, TKFC, TMEM126A, TMEM126B, TMEM165, TMEM199, TMEM65, TMEM70, TNPO3, TOMM7, TOP3A, TPK1, TPMT, TPP1, TRAP1, TRAPPC11, TREX1, TRIM32, TRIM37, TRIT1, TRMT10C, TRMT5, TRMU, TRNT1, TRPM6, TRPM7, TSFM, TTC19, TTC37, TTPA, TUFM, TUSC3, TWNK, TYMP, UCP2, UGGT1, UGT1A1, UMOD, UMPS, UPB1, UQCC2, UQCC3, UQCRB, UQCRC1, UQCRC2, UQCRFS1, UQCRQ, UROC1, UROD, UROS, VARS2, VIPAS39, VKORC1, VPS16, VPS33A, VPS33B, WARS2, WDR45, WFS1, XDH, XPNPEP3, XYLT1, XYLT2, YARS2, YME1L1, ZMPSTE24, ZNF143

ClinVar P/LP variants (IDs) not covered: AGL:[4529480] | CFTR:[1705266]; [3385381]; [3572906]; [818230]; [4279028] | CYP11B1:[4281641] | DMD:[3235708]; [4292852]; [4277362]; [2637520] | GABRG2:[3757681] | GALNS:[3600992]; [3600991] | GALT:[4541441] | GLA:[1678527] | GNE:[4068787] | HADHB:[3359235] | HPRT1:[4532158] | HPS1:[4077138] | IDUA:[2507023]; [3393459] | MAN2B1:[3024226] | OTC:[4072311] | PAH:[242452] | PANK2:[3897668] | PEX14:[3663959] | RAI1:[1321231] | SERAC1:[4526663] | SGCB:[4277883] | SSR4:[1878509] | TK2:[3778875]

GC_73 Mitochondrial Disorder

Mitochondrial disorders are genetically heterogeneous diseases caused by impaired mitochondrial function and energy production. They commonly affect tissues with high energy demands, including the nervous system, skeletal muscle, heart, liver, kidneys, eyes, ears, and endocrine system, and may present as isolated organ involvement or multisystem disease.

This panel includes nuclear and mitochondrial genes associated with the major molecular pathways underlying mitochondrial disease, including oxidative phosphorylation, mitochondrial DNA maintenance and replication, mitochondrial translation, coenzyme Q10 biosynthesis, mitochondrial dynamics, and related metabolic pathways. Representative genes include POLG, SURF1, TWNK, TK2, OPA1, MFN2, COQ genes, and MT-ATP6. It also includes genes associated with well-established mitochondrial phenotypes such as MELAS, MERRF, Leigh syndrome, LHON, NARP, and maternally inherited mitochondrial hearing loss.

This panel is recommended for patients with suspected mitochondrial disease, particularly those with multisystem involvement or an unexplained combination of neurologic, muscular, cardiac, metabolic, ophthalmologic, auditory, hepatic, renal, or endocrine abnormalities suggestive of mitochondrial dysfunction.

Last update: 07.01.2026

AARS2, AASS, ABAT, ABCB7, ACACA, ACAD9, ACADM, ACADS, ACADVL, ACAT1, ACO2, ADAR, AFG3L2, AGK, AIFM1, AK2, ALAS2, ALDH3A2, AMPD1, AMT, ANO10, APTX, ATAD3A, ATP5F1A, ATP5F1B, ATP5F1C, ATP5F1D, ATP5F1E, ATP5MC1, ATP5MC2, ATP5MC3, ATP5ME, ATP5MK, ATP5PF, ATP5PO, ATP7B, ATPAF2, AUH, BAG3, BCS1L, BOLA3, BTD, C10ORF2, C12ORF65, C19ORF12, C19ORF70, C1QBP, C2orf69, CA5A, CARS2, CEP89, CHAT, CHCHD10, CLPB, CLPP, CMPK2, COA1, COA3, COA5, COA6, COA7, COA8, COASY, COQ2, COQ4, COQ5, COQ6, COQ7, COQ8A, COQ8B, COQ9, COX10, COX11, COX14, COX15, COX16, COX18, COX20, COX4I1, COX4I2, COX5A, COX5B, COX6A1, COX6A2, COX6B1, COX6C, COX7A1, COX7B, COX7C, COX8A, CPS1, CPT1A, CPT2, CRAT, CRLS1, CYC1, CYCS, D2HGDH, DARS2, DCC, DES, DGUOK, DLAT, DLD, DNA2, DNAJC19, DNAJC30, DNM1L, DNM2, EARS2, ECHS1, ELAC2, ERAL1, ETFA, ETFB, ETFDH, ETHE1, FARS2, FASTKD2, FBXL4, FDX2, FDXR, FH, FLAD1, FOXRED1, GAMT, GARS1, GATB, GATC, GATM, GCDH, GDAP1, GFER, GFM1, GFM2, GLDC, GLRX5, GTPBP3, GUK1, GYG2, HADH, HADHA, HADHB, HARS2, HCCS, HIBCH, HLCS, HMGCL, HMGCS2, HPDL, HSD17B10, HSPA9, HSPD1, HTRA2, IARS2, IBA57, IDH1, IDH2, IDH3A, IDH3B, IFIH1, ISCA1, ISCA2, ISCU, KARS1, KIF5A, L2HGDH, LAMP2, LARS1, LARS2, LETM1, LIAS, LIG3, LIPT1, LIPT2, LMBRD1, LONP1, LRPPRC, LYRM4, LYRM7, MARS2, MDH2, MECR, MFF, MFN2, MGME1, MICOS13, MICU1, MICU2, MIEF2, MIPEP, MORC2, MPC1, MPV17, MRM2, MRPL12, MRPL3, MRPL39, MRPL40, MRPL44, MRPL49, MRPS14, MRPS16, MRPS2, MRPS22, MRPS23, MRPS25, MRPS28, MRPS34, MRPS7, MSTO1, MT-ATP6, MT-ATP8, MT-CO1, MT-CO2, MT-CO3, MT-CYB, MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L, MT-ND5, MT-ND6, MT-RNR1, MT-RNR2, MT-TA, MT-TC, MT-TD, MT-TE, MT-TF, MT-TG, MT-TH, MT-TI, MT-TK, MT-TL1, MT-TL2, MT-TM, MT-TN, MT-TP, MT-TQ, MT-TR, MT-TS1, MT-TS2, MT-TT, MT-TV, MT-TW, MT-TY, MTFMT, MTHFD1, MTO1, MTPAP, MTRFR, NADK2, NARS2, NAXD, NAXE, NDUFA1, NDUFA10, NDUFA11, NDUFA12, NDUFA13, NDUFA2, NDUFA3, NDUFA4, NDUFA5, NDUFA6, NDUFA7, NDUFA8, NDUFA9, NDUFAB1, NDUFAF1, NDUFAF2, NDUFAF3, NDUFAF4, NDUFAF5, NDUFAF6, NDUFAF8, NDUFB1, NDUFB10, NDUFB11, NDUFB2, NDUFB3, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFB8, NDUFB9, NDUFC1, NDUFC2, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS5, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV2, NDUFV3, NFS1, NFU1, NGLY1, NNT, NR2F1, NSUN3, NUBPL, NUP62, OGDH, OPA1, OPA3, OTC, OXA1L, OXCT1, PANK2, PARS2, PC, PCCA, PCCB, PCK2, PDE12, PDHA1, PDHB, PDHX, PDK3, PDP1, PDSS1, PDSS2, PET100, PET117, PINK1, PITRM1, PLA2G6, PMPCA, PMPCB, PNKD, PNPLA8, PNPT1, POLG, POLG2, POLRMT, POP1, PPA2, PPOX, PRORP, PSAP, PTCD3, PTPMT1, PUS1, QARS1, QRSL1, RANBP2, RARS1, RARS2, REEP1, RMND1, RNASEH1, RNASEH2A, RNASEH2B, RNASEH2C, RRM2B, RTN4IP1, SACS, SAMHD1, SARS2, SCN1A, SCO1, SCO2, SDHA, SDHAF1, SDHAF2, SDHB, SDHC, SDHD, SERAC1, SFXN4, SIRT1, SLC13A3, SLC19A2, SLC19A3, SLC22A5, SLC25A1, SLC25A10, SLC25A12, SLC25A13, SLC25A15, SLC25A19, SLC25A20, SLC25A21, SLC25A22, SLC25A24, SLC25A26, SLC25A3, SLC25A32, SLC25A36, SLC25A38, SLC25A4, SLC25A42, SLC25A46, SLC39A8, SLC52A2, SLC52A3, SLC6A8, SLC7A13, SPAST, SPATA5, SPG7, SQOR, SSBP1, STAT2, STXBP1, SUCLA2, SUCLG1, SUCLG2, SUGCT, SUPV3L1, SURF1, TACO1, TAFAZZIN, TAMM41, TANGO2, TARS2, TEFM, TFAM, TIMM22, TIMM50, TIMM8A, TIMMDC1, TK2, TMEM126A, TMEM126B, TMEM65, TMEM70, TOMM7, TOMM70, TOP1MT, TOP3A, TPK1, TRAP1, TREX1, TRIT1, TRMT10C, TRMT5, TRMU, TRNT1, TSFM, TTC19, TUFM, TWNK, TXN2, TYMP, UQCC2, UQCC3, UQCRB, UQCRC1, UQCRC2, UQCRFS1, UQCRH, UQCRQ, VARS2, VPS13D, WARS2, WDR45, WFS1, XPNPEP3, YARS2, YME1L1 CONTENTS

GC_76 Hyperammonaemia

Hyperammonaemia is characterized by elevated blood ammonia concentrations and may result in encephalopathy, seizures, developmental impairment, or life-threatening metabolic decompensation. It may arise from primary urea cycle defects or secondary impairment of ammonia metabolism caused by other inherited metabolic disorders.

This panel includes genes associated with the major inherited causes of hyperammonaemia, including urea cycle disorders, organic acidemias, fatty acid oxidation disorders, mitochondrial diseases, and other metabolic conditions that may impair ammonia detoxification.

This panel is recommended for patients with unexplained hyperammonaemia, metabolic encephalopathy, recurrent vomiting, episodic metabolic decompensation, or other clinical or biochemical findings suggestive of an inherited hyperammonaemic disorder.

Last update: 07.01.2026

ABCD4, ACADM, ACADS, ACADVL, ALDH18A1, AMT, ARG1, ASL, ASS1, ATP5F1A, ATP5F1D, ATP5F1E, ATPAF2, AUH, BCKDHA, BCKDHB, BTD, CA5A, CPS1, CPT1A, CPT2, CYC1, DBT, DLAT, DLD, ETFA, ETFB, ETFDH, FBXL4, GLDC, GLUD1, GLUL, HADHA, HADHB, HCFC1, HLCS, HMGCL, HMGCS2, IVD, LMBRD1, LYRM7, MCCC1, MCCC2, MCEE, MLYCD, MMAA, MMAB, MMACHC, MMADHC, MMUT, MTR, MTRR, NAGS, NBAS, NR1H4, OAT, OTC, PC, PCCA, PCCB, PDHA1, PDHB, PDHX, PDP1, POLG, PRDX1, PYGM, RINT1, SERAC1, SLC22A5, SLC25A13, SLC25A15, SLC25A20, SLC25A42, SLC7A7, SUCLA2, SUCLG1, TAFAZZIN, TANGO2, TMEM70, TUFM, UMPS, UQCRC2, YARS2

ClinVar P/LP variants (IDs) not covered: HADHB:[3359235] | OTC:[4072311] | SERAC1:[4526663]