Table 3.
Metabolic epilepsies according to the International Classification of Inherited Metabolic Disorders (ICIMD).
| Groups of IMDs and Genes | Number and Percentage of Metabolic Epilepsies vs. Number of All Described IMDs in the ICIMD Group |
|---|---|
| INTERMEDIARY METABOLISM: NUTRIENTS | |
| Disorders of amino acid metabolism | 53/111 (48%) |
| Urea cycle disorders and inherited hyperammonemias, organic acidurias and disorders of branched-chain amino acid metabolism | 24/33 (73%) |
| NAGS, CPS1, OTC, ASS1, ASL, ARG1, SLC25A15, GLUD1, IVD, ACAD8, ACADSB, MCCC1, MCCC2, AUH, ECHS1, HIBCH, PCCA, PCCB, GCDH, MLYCD, BCKDHA, BCKDHB, DBT, BCKDK | |
| Disorders of glycine and serine metabolism, glutamate/glutamine and aspartate/asparagine metabolism | 13/15 (87%) |
| GLDC, AMT, PHGDH, PSAT1, PSPH, SLC1A4, GPT2, GAD1, GLUL, GLS, ASNS, NAT8L, ASPA | |
| Other disorders of amino acid metabolism (phenylalanine and tyrosine, sulfur-containing amino acids and hydrogen sulfide, ornithine, proline and hydroxyproline, amino acid transport) | 15/61 (25%) |
| PAH, ADK, MTR, CBS, SQOR, ETHE1, SUOX, PYCR2, PRODH, ALDH4A1, AASS, SLC6A19, SLC1A3, SLC1A2, SLC6A1, ACY1 | |
| Disorders of peptide and amine metabolism | 6/21 (29%) |
| GSS, XPNPEP3, ODC1, SMS | |
| Disorders of carbohydrate metabolism | 17/68 (25%) |
| ALDOB, GLYCTK, FBP1, PC, PCK1, GK, HK1, GCK, PGK1, GYS1, GYS2, EPM2A, NHLRC1, RPIA, SLC2A1, SLC45A1, SLC17A5 | |
| Disorders of fatty acid and ketone body metabolism | 9/27 (33%) |
| CPT1A, CPT2, SLC25A20, ACADS, ACADM, HADH, HADHA, HMGCL, SLC16A1 | |
| INTERMEDIARY METABOLISM: ENERGY | |
| Disorders of energy substrate metabolism | 19/29 (66%) |
| PDHA1, PDHB, DLAT, DLD, PDHX, PDP1, MPC1, ACO2, IDH2, IDH3A, SUCLA2, SUCLG1, FH, MDH2, SLC13A5, OGDHL, GATM, GAMT, SLC6A8 | |
| mtDNA-related disorders | 30/37 (81%) |
| MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND5, MT-ND6, MT-CYB, MT-CO1, MT-CO2, MT-CO3, MT-ATP6, MT-ATP8, MT-TR, MT-TN, MT-TC, MT-TQ, MT-TH, MT-TI, MT-TL1, MT-TL2, MT-TK, MT-TM, MT-TF, MT-TP, MT-TS1, MT-TS2, MT-TT, MT-TW, MT-TY, MT-TV | |
| Nuclear-encoded disorders of oxidative phosphorylation | 43/95 (45%) |
| NDUFV1, NDUFV2, NDUFS1, NDUFS4, NDUFS6, NDUFS7, NDUFS8, NDUFA1, NDUFA2, NDUFA8, NDUFA11, NDUFB8, NDUFB11, NDUFC2, NDUFAF2, NDUFAF3, NDUFAF4, NDUFAF5, NDUFAF6, NDUFAF8, FOXRED1, NUBPL, TIMMDC1, SDHA, SDHD, UQCC2, CYC1, HCCS, BCS1L, COX4I1, COX6B1, COX8A, NDUFA4, COX10, COX15, SCO2, LRPPRC, PET100, FASTKD2, APOPT1, ATP5F1A, ATP5F1D, TMEM70 | |
| Disorders of mitochondrial cofactor biosynthesis, mitochondrial DNA maintenance and replication, mitochondrial gene expression, other disorders of mitochondrial function | 67/164 (41%) |
| PDSS2, COQ2, COQ4, COQ5, COQ6, COQ8A, COQ9, LIPT2, LIAS, BOLA3, IBA57, ISCA1, NFS1, DGUOK, RRM2B, SAMHD1, POLG, POLG2, TWNK, HSD17B10, TRNT1, MTFMT, GTPBP3, MTO1, TRIT1, RARS2, NARS2, CARS2, EARS2, IARS2, LARS2, FARS2, PARS2, VARS2, WARS2, KARS2, MRPL12, MRPS22, MRM2, RMND1, GFM1, GFM2, TSFM, GUF1, SLC25A1, SLC25A10, SLC25A12, GOT2, MDH1, SLC25A22, MICU1, TIMM50, PMPCB, MIPEP, CLPB, CLPP, LONP1, HSPD1, FBXL4, AFG3L2, ATAD3A, HTRA2, PPA2, TXN2, AIFM1, RTN4IP1, PTRH2 | |
| INTERMEDIARY METABOLISM: OTHERS | |
| Disorders of metabolite repair/proofreading | 3/4 (75%) |
| D2HGDH, L2HGDH, ACSF3 | |
| LIPID METABOLISM AND TRANSPORT | |
| Disorders of lipid metabolism | 37/151 (25%) |
| ELOVL4, ABCD1, ACOX1, HSD17B4, BSCL2, CHKB, PCYT2, MBOAT7, PLA2G6, DDHD2, MFSD2A, FIG4, OCRL, SYNJ1, PIK3CA, PIK3R2, PI4K2A, PTEN, INPP5K, PLCB1, PLCH1, PEX7, FAR1, PEX5, CERS1, DEGS1, FA2H, SGPL1, FDFT1, LSS, NSDHL, EBP, DHCR24, DHCR7, CYP27A1, AMACR | |
| Disorders of lipoprotein metabolism | 1/31 (3%) |
| VLDLR | |
| METABOLISM OF HETEROCYCLIC COMPOUNDS | |
| Disorders of nucleobase, nucleotide and nucleic acid metabolism | 55/161 (34%) |
| Disorders of pyrimidine, purine, ectonucleotide and nucleic acid metabolism, disorders of ribosomal biogenesis | 23/117 (20%) |
| CAD, DPYD, DPYS, UPB1, PRPS1, ADSL, ATIC, AMPD2, ADA2, ITPA, TREX1, RNASEH2A, RNASEH2B, RNASEH2C, RNASET2, ADARB1, IFIH1, POLR3A, POLR3B, UBTF, SNORD118, EMG1, RPL10 | |
| Disorders of non-mitochondrial tRNA processing and aminoacyl-tRNA synthetases | 32/44 (73%) |
| TSEN2, TSEN15, TSEN34, TSEN54, CLP1, TRMT10A, TRMT1, DALRD3, NSUN2, ADAT3, LAGE3, OSGEP, TP53RK, TPRKB, PUS3, WDR4, AARS1, RARS1, NARS1, CARS1, QARS1, EPRS1, IARS1, LARS1, KARS1, FARSB, SARS1, YARS1, VARS1, AIMP1, AIMP2, NUP133 | |
| Disorders of tetrapyrrole metabolism | 1/19 (5%) |
| HMBS | |
| COMPLEX MOLECULE AND ORGANELLE METABOLISM | |
| Congenital disorders of glycosylation | 81/144 (56%) |
| Disorders of N-linked and O-linked protein glycosylation | 20/33 (61%) |
| PMM2, DPAGT1, ALG13, ALG14, ALG1, ALG2, ALG11, RFT1, ALG3, ALG9, ALG6, STT3A, STT3B, OSTC, SSR4, MOGS, MAN1B1, MGAT2, FUT8, FCSK, POMT1, POMT2, POMGNT1, B3GALNT2, POMK, FKTN, FKRP, B4GAT1, EXT2, EXTL3, NDST1, HS6ST2 | |
| Disorders of lipid glycosylation | 25/27 (93%) |
| PIGA, PIGC, PIGQ, PIGH, PIGP, PIGY, PIGL, PIGW, PIGM, PIGV, PIGN, PIGB, PIGO, PIGF, PIGG, PIGT, PIGS, PIGU, PIGK, GPAA1, PGAP1, PGAP3, PGAP2, ST3GAL5, ST3GAL3 | |
| Disorders of multiple glycosylation pathways, other disorders of glycan metabolism | 24/36 (67%) |
| DHDDS, NUS1, DOLK, DPM1, DPM2, DPM3, MPDU1, SLC35A1, SLC35A2, SLC35A3, SLC35C1, ATP6V0A2, ATP6V1A, ATP6AP1, ATP6AP2, CCDC115, TMEM165, GNE, NANS, PGM1, GMPPB, UGDH, UGP2, NGLY1 | |
| Disorders of organelle biogenesis, dynamics and interactions | 60/119 (51%) |
| SERAC1, PISD, MICOS13, DNM1L, MFF, SPATA5, STAT2, SLC25A46, TRAK1, PEX1, PEX2, PEX3, PEX5, PEX6, PEX10, PEX12, PEX13, PEX19, PEX26, VPS11, AP3D1, LYST, MYO5A, RAB27A, BCAP31, COL4A3BP, VPS13A, VPS13B, COG2, COG4, COG4, COG5, COG6, COG7, COG8, ARCN1, TRAPPC2L, TRAPPC4, TRAPPC6B, TRAPPC9, TRAPPC11, TRAPPC12, GOSR2, VPS4A, VPS41, YIF1B, TANGO2, SCYL2, STX11, STXBP2, ARFGEF2, AP1S2, AP3B2, AP4B1, AP4E1, AP4M1, AP4S1, RUBCN, RAB18, AP1G1 | |
| Disorders of complex molecule degradation | 43/75 (57%) |
| Disorders of sphingolipid degradation | 11/17 (65%) |
| GBA, SMPD4, HEXA, HEXB, GM2A, GALC, ARSA, SUMF1, GLA, ASAH1, PSAP | |
| Disorders of glycosaminoglycan degradation, Disorders of glycoprotein degradation, and Other disorders of complex molecule degradation | 14/33 (42%) |
| IDS, SGSH, NAGLU, HGSNAT, GNS, NEU1, CTSA, MANBA, NAGA, FUCA1, AGA, SCARB2, NPC1, NPC2 | |
| Neuronal ceroid lipofuscinosis | 12/13 (93%) |
| PPT1, TPP1, CLN3, DNAJC5, CLN5, CLN6, MFSD8, CLN8, CTSD, ATP13A2, CTSF, KCTD7 | |
| Disorders of autophagy | 6/12 (50%) |
| EPG5, WDR45, SNX14, SPG11, TECPR2, TBCK | |
| COFACTOR AND MINERAL METABOLISM | |
| Disorders of vitamin and cofactor metabolism | 35/73 (48%) |
| GCH1, PTS, SPR, QDPR, SLC19A2, SLC19A3, TPK1, NADK2, NAXD, NAXE, NNT, PANK2, SLC25A42, ALDH7A1, PNPO, PLPBP, ALPL, BTD, HLCS, SLC5A6, SLC46A1, FOLR1, MTHFR, MTHFD1, MTHFS, DHFR, LMBRD1, MMACHC, MMADHC, MMAA, MTRR, HCFC1, MOCS1, MOCS2, GPHN | |
| Disorders of trace elements and metals | 5/36 (14%) |
| ATP7A, SLC33A1, FTL, SLC39A8, SEPSECS | |
| METABOLIC CELL SIGNALING | |
| Neurotransmitter disorders | 40/69 (58%) |
| Disorders of monoamine neurotransmission, γ-aminobutyric acid neurotransmitter disorders, glutamate neurotransmitter disorders | 19/32 (60%) |
| TH, DBH, ABAT, ALDH5A1, GABRA1, GABRB1, GABRB2, GABRB3, GABRG2, GABBR2, GRIN1, GRIN2A, GRIN2B, GRIN2D, GRIA2, GRIA3, GRIA4, ATAD1, GRM1 | |
| Disorders of the synaptic vesicle cycle | 18/29 (62%) |
| TBC1D24, KIF1A, KIF5A, KIF5C, DYNC1H1, DNM1, PRRT2, SNAP25, SNAP29, STXBP1, SV2A, VAMP2, STX1B, SYN1, IL1RAPL1, DNAJC6, CLTC, DLG4 | |
| Endocrine metabolic disorders | 4/50 (8%) |
| ABCC8, KCNJ11, AKT2, MC2R | |
Note: in bold—ICIMD groups, in italic—ICIMD subgroups.