Table 4.
Treatable metabolic epilepsies.
| Name of the Disorder | Genes | MIM# Number | Treatment Strategy |
|---|---|---|---|
| INTERMEDIARY METABOLISM: NUTRIENTS | |||
| N-acetylglutamate synthase deficiency | NAGS | # 237310 | Nutritional, pharmacological, solid organ transplantation, hemodialysis/peritoneal dialysis |
| Carbamoyl phosphate synthetase 1 deficiency | CPS1 | # 237300 | Nutritional, pharmacological, solid organ transplantation, hemodialysis/peritoneal dialysis |
| Ornithine transcarbamylase deficiency | OTC | # 311250 | Nutritional, pharmacological, solid organ transplantation, hemodialysis/peritoneal dialysis |
| Argininosuccinate synthetase deficiency | ASS1 | # 215700 | Nutritional, pharmacological, solid organ transplantation, hemodialysis/peritoneal dialysis |
| Argininosuccinate lyase deficiency | ASL | # 207900 | Nutritional, pharmacological, solid organ transplantation, hemodialysis/peritoneal dialysis |
| Arginase deficiency | ARG1 | # 207800 | Nutritional, pharmacological, solid organ transplantation, hemodialysis/peritoneal dialysis |
| Mitochondrial ornithine transporter deficiency | SLC25A15 | # 238970 | Nutritional, pharmacological, solid organ transplantation, hemodialysis/peritoneal dialysis |
| Isovaleryl-CoA dehydrogenase deficiency | IVD | # 243500 | Nutritional, pharmacological |
| Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency | ECHS1 | # 616277 | Nutritional |
| 3-hydroxyisobutyryl-CoA hydrolase deficiency | HIBCH | # 250620 | Nutritional |
| Propionic acidemia due to propionyl-CoA carboxylase subunit α or β deficiency | PCCA, PCCB | # 606054 | Nutritional, pharmacological, solid organ transplantation, hemodialysis/peritoneal dialysis |
| Glutaryl-CoA dehydrogenase deficiency | GCDH | # 231670 | Nutritional |
| Branched-chain ketoacid dehydrogenase E1 α/E1 β/dihydrolipoyl transacylase deficiency | BCKDHA, BCKDHB, DBT | # 248600 | Nutritional, vitamin or trace element, hemodialysis/peritoneal dialysis, solid organ transplantation |
| Branched-chain ketoacid dehydrogenase kinase deficiency | BCKDK | # 614923 | Nutritional |
| Phenylalanine hydroxylase deficiency | PAH | # 261600 | Nutritional, pharmacological, enzyme replacement |
| Methionine synthase deficiency | MTR | # 250940 | Vitamin or trace element |
| Cystathionine β-synthase deficiency | CBS | # 236200 | Nutritional, vitamin or trace element |
| Nonketotic hyperglycinemia due to glycine decarboxylase/aminomethyltransferase deficiency | GLDC, AMT | # 605899 | Pharmacological |
| 3-phosphoglycerate dehydrogenase deficiency | PHGDH | # 601815 | Nutritional |
| Phosphoserine aminotransferase deficiency | PSAT1 | # 610992 | Nutritional |
| Phosphoserine phosphatase deficiency | PSPH | # 614023 | Nutritional |
| Glutamine synthetase deficiency | GLUL | # 610015 | Nutritional |
| 3-hydroxy-3-methylglutaryl-CoA lyase deficiency | HMGCL | # 246450 | Nutritional |
| INTERMEDIARY METABOLISM: ENERGY | |||
| GLUT1 deficiency | SLC2A1 | # 606777; # 612126 |
Nutritional, pharmacological |
| Pyruvate dehydrogenase E1 α/E1 β/E3-binding protein/dihydrolipoamide acetyltransferase/dihydrolipoamide dehydrogenase deficiency | PDHA1, PDHB, DLAT, DLD, PDHX | # 312170; # 614111; # 245348; # 246900; # 245349 |
Nutritional, vitamin or trace element |
| Pyruvate dehydrogenase phosphatase deficiency | PDP1 | # 608782 | Nutritional |
| Arginine:glycine amidinotransferase (AGAT) deficiency | GATM | # 612718 | Nutritional |
| Guanidinoacetate methyltransferase deficiency | GAMT | # 612736 | Nutritional |
| Creatine transporter deficiency | SLC6A8 | # 300352 | Nutritional |
| NADH dehydrogenase core subunit 1/subunit 4/subunit 5/subunit 6/cytochrome c oxidase subunit 1/ mitochondrial tRNA-Gln/tRNA-His/tRNA-Leu 1/tRNA-Phe/tRNA-Ser 1/tRNA-Ser 2/tRNA-Trp deficiency | MT-ND1, MT-ND4, MT-ND5, MT-ND6, MT-CO1, MT-TQ, MT-TH, MT-TL1, MT-TF, MT-TS1, MT-TS2, MT-TW | # 540000 | Nutritional |
| Coenzyme Q5 methyltransferase/Q8A (ADCK3) deficiency | COQ5, COQ8A | # 619028; # 612016 |
Vitamin or trace element |
| Mitochondrial aspartate-glutamate carrier isoform 1 deficiency | SLC25A12 | # 612949 | Nutritional |
| Mitochondrial aspartate aminotransferase deficiency | GOT2 | # 618721 | Nutritional, vitamin or trace element |
| LIPID METABOLISM AND TRANSPORT | |||
| X-linked adrenoleukodystrophy | ABCD1 | # 300100 | Gene-based, stem cell |
| 7-dehydrocholesterol reductase deficiency | DHCR7 | # 270400 | Nutritional, pharmacological |
| Sterol 27-hydroxylase deficiency | CYP27A1 | # 213700 | Pharmacological |
| METABOLISM OF HETEROCYCLIC COMPOUNDS | |||
| CAD trifunctional protein deficiency | CAD | # 616457 | Pharmacological |
| Phosphoribosylpyrophosphate synthetase deficiency | PRPS1 | # 301835 | Pharmacological |
| Isoleucyl-tRNA synthetase 1 deficiency | IARS1 | # 617093 | Nutritional |
| Leucyl-tRNA synthetase 1 deficiency | LARS1 | # 615438 | Nutritional |
| Phenylalanyl-tRNA synthetase subunit β deficiency | FARSB | # 613658 | Nutritional |
| Seryl-tRNA synthetase 1 deficiency | SARS1 | # 617709 | Nutritional |
| COMPLEX MOLECULE AND ORGANELLE METABOLISM | |||
| PMM2-CDG | PMM2 | # 212065 | Pharmacological |
| PIGA-CDG | PIGA | # 300868 | Nutritional |
| PIGM-CDG | PIGM | # 610293 | Pharmacological |
| PIGO-CDG | PIGO | # 614749 | Vitamin or trace element |
| SLC35A2-CDG | SLC35A2 | # 300896 | Nutritional |
| SLC35C1-CDG | SLC35C1 | # 266265 | Nutritional |
| Arylsulfatase A deficiency | ARSA | # 250100 | Gene-based, stem cell |
| Iduronate sulfatase deficiency | IDS | # 309900 | Stem cell |
| α-fucosidase deficiency | FUCA1 | # 230000 | Stem cell |
| Aspartylglucosaminidase deficiency | AGA | # 208400 | Stem cell |
| Tripeptidyl-peptidase 1 deficiency | TPP1 | # 204500 | Enzyme replacement |
| CLN7 disease | MFSD8 | # 610951 | Gene-based |
| Niemann–Pick disease type C1/type C2 | NPC1, NPC2 | # 257220; # 607625 |
Pharmacological |
| COFACTOR AND MINERAL METABOLISM | |||
| Autosomal recessive GTP cyclohydrolase 1 deficiency | GCH1 | # 233910 | Nutritional, vitamin or trace element, pharmacological |
| Sepiapterin reductase deficiency | SPR | # 612716 | Pharmacological, vitamin or trace element |
| Dihydropteridine reductase deficiency | QDPR | # 261630 | Nutritional, pharmacological, vitamin or trace element |
| Thiamine transporter 2 deficiency | SLC19A3 | # 607483 | Vitamin or trace element |
| Thiamine pyrophosphokinase deficiency | TPK1 | # 614458 | Vitamin or trace element |
| NAD(P)HX epimerase deficiency | NAXE | # 617186 | Vitamin or trace element |
| α-aminoadipic semialdehyde dehydrogenase deficiency | ALDH7A1 | # 266100 | Vitamin or trace element, nutritional |
| Pyridoxamine 5′-phosphate oxidase deficiency | PNPO | # 610090 | Vitamin or trace element |
| PROSC deficiency | PLPBP | # 617290 | Vitamin or trace element |
| Biotinidase deficiency | BTD | # 253260 | Vitamin or trace element |
| Holocarboxylase synthetase deficiency | HLCS | # 253270 | Vitamin or trace element |
| Sodium-dependent multivitamin transporter deficiency | SLC5A6 | # 618973 | Vitamin or trace element |
| Proton-coupled folate transporter deficiency | SLC46A1 | # 229050 | Vitamin or trace element |
| Folate receptor α deficiency | FOLR1 | # 613068 | Vitamin or trace element |
| 5,10-methylenetetrahydrofolate reductase deficiency | MTHFR | # 236250 | Nutritional, vitamin or trace element |
| 5,10-methenyltetrahydrofolate synthetase deficiency | MTHFS | # 618367 | Vitamin or trace element |
| Dihydrofolate reductase deficiency | DHFR | # 613839 | Vitamin or trace element |
| Methylmalonic aciduria and homocystinuria, cblF type | LMBRD1 | # 277380 | Vitamin or trace element |
| Methylmalonic aciduria and homocystinuria, cblC type, cblD type | MMACHC, MMADHC | # 277400; # 277410 |
Nutritional, vitamin or trace element |
| Methylmalonic aciduria, cblA type | MMAA | # 251100 | Nutritional, vitamin or trace element, pharmacological, hemodialysis/peritoneal dialysis, solid organ transplantation |
| Methionine synthase reductase deficiency | MTRR | # 236270 | Vitamin or trace element |
| Cyclic pyranopterin monophosphate synthase deficiency | MOCS1 | # 252150 | Pharmacological |
| Copper-transporting ATPase subunit α deficiency | ATP7A | # 309400 | Pharmacological, vitamin or trace element |
| SLC39A8 deficiency | SLC39A8 | # 616721 | Nutritional |
| METABOLIC CELL SIGNALING | |||
| Tyrosine hydroxylase deficiency | TH | # 605407 | Pharmacological |
| Succinic semialdehyde dehydrogenase deficiency | ALDH5A1 | # 271980 | Pharmacological |
| Ionotropic glutamate receptor NMDA type subunit 1 dysregulation | GRIN1 | # 617820; # 614254 |
Pharmacological |
| Ionotropic glutamate receptor NMDA type subunit 2A dysregulation | GRIN2A | # 245570 | Pharmacological |
| Ionotropic glutamate receptor NMDA type subunit 2B dysregulation | GRIN2B | # 613970 | Nutritional |
| Ionotropic glutamate receptor NMDA type subunit 2D superactivity | GRIN2D | # 617162 | Pharmacological |
| ATP-sensitive potassium channel regulatory subunit superactivity | ABCC8 | # 256450 | Pharmacological |
| ATP-sensitive potassium channel pore-forming subunit superactivity | KCNJ11 | # 618856 | Pharmacological |
| AKT2 superactivity | AKT2 | # 240900 | Pharmacological |
| ACTH receptor deficiency | MC2R | # 202200 | Pharmacological |