From: Treatable inherited metabolic disorders causing intellectual disability: 2021 review and digital app
Name of disorder | Treatment strategy | Treatment | Level of evidence | Effect of treatment | ReferenceS |
---|---|---|---|---|---|
3-hydroxy-3-methylglutaryl-CoA lyase deficiency | Nutritional therapy | Protein defined diet, avoid fasting, sick day management | 5 | C | [57] |
3-hydroxyisobutyryl-CoA hydrolase deficiency (synonym: beta-hydroxyisobutyryl-CoA deacylase deficiency) | Nutritional therapy | Valine restriction | 4 | A, E, G | [58] |
3-phosphoglycerate dehydrogenase deficiency | Nutritional therapy | L-Serine, glycine | 4 | D, E, F | [59] |
5,10-methenyltetrahydrofolate synthetase deficiency (synonym: 5-formyltetrahydrofolate cycloligase deficiency) | Vitamin & trace element | 5-methyltetrahydrofolate, methylcobalamin | 5 | E | [60] |
5,10-methylenetetrahydrofolate reductase deficiency | Nutritional therapy | Carnitine, methionine | 4 | C, D, G | [61] |
Vitamin & trace element | Betaine, folate ± | 4 | C, D, G | [61] | |
6-pyruvoyl-tetrahydropterin synthase deficiency | Nutritional therapy | Phenylalanine-reduced diet ± | 4 | D, E | [62] |
Vitamin & trace element | Folinic acid ± | 4 | A, E, F | [62] | |
Pharmacological therapy | L-dopa + carbidopa, 5-Hydroxytryptophan, sapropterin dihydrochloride (synthetic BH4) co-factor therapy | 4 | A, B, E, F, G | [62] | |
7-dehydrocholesterol reductase deficiency | Nutritional therapy | Cholesterol | 4 | G | |
Pharmacological therapy | Simvastatin | 1b | B | ||
ACAD9 deficiency | Vitamin & trace element | Riboflavin | 4 | A, E | [65] |
Alpha-aminoadipic semialdehyde dehydrogenase deficiency (synonym: pyridoxine-dependent epilepsy) | Nutritional therapy | Lysine restriction, arginine | 4 | A, D, E, F | [66] |
Vitamin & trace element | Pyridoxine | 4 | A, D, E, F | [66] | |
Alpha-fucosidase deficiency | Stem cell therapy | (Umbilical cord/bone marrow) hematopoietic stem cell transplantation | 4 | D, E, G | [67] |
Alpha-iduronidase deficiency (synonyms: Hurler syndrome [severe]; Scheie syndrome [attenuated]) | Enzyme replacement therapy | Intrathecal iduronidase | 2b | A, D, G | |
Stem cell therapy | Hematopoietic stem cell transplantation | 1c | D, G | ||
Alpha-mannosidase deficiency | Enzyme replacement therapy | Velmanase alfa | 1c | D | |
Stem cell therapy | Hematopoietic stem cell transplantation | 4 to 5 | D, E | ||
Arginase deficiency (synonym: argininemia) | Nutritional therapy | Protein defined diet, arginine or citrulline | 2b, effect on growth 4 | B, C, D, E, G | [72] |
Pharmacological therapy | Sodium phenylbutyrate, glycerol phenylbutyrate, sodium benzoate | 2b | B, C, D, E | [72] | |
Other | Hemodialysis, peritoneal dialysis | 4 | D | [72] | |
Solid organ transplant | Liver transplantation | 4 | A, B, D, E | [72] | |
Arginine:glycine amidinotransferase (AGAT) deficiency | Nutritional therapy | Creatine | 4 | A, D, E | [73] |
Argininosuccinate lyase deficiency | Nutritional therapy | Protein defined diet, arginine or citrulline | 2b, effect on growth 4 | B, C, D, E, G | [72] |
Pharmacological therapy | Sodium phenylbutyrate, glycerol phenylbutyrate, sodium benzoate | 2b | B, C, D, E | [72] | |
Other | Hemodialysis, peritoneal dialysis | 4 | D | [72] | |
Solid organ transplant | Liver transplantation | 4 | A, B, D, E, systemic phenotype persists | [72] | |
Argininosuccinate synthetase deficiency (synonym: citrullinemia type 1) | Nutritional therapy | Protein defined diet, arginine or citrulline | 2b, effect on growth 4 | B, C, D, E, G | [72] |
Pharmacological therapy | Sodium phenylbutyrate, glycerol phenylbutyrate, sodium benzoate | 2b | B, C, D, E | [72] | |
Other | Hemodialysis, peritoneal dialysis | 4 | D | [72] | |
Solid organ transplant | Liver transplantation | 4 | A, B, D, E | [72] | |
Aromatic L-amino acid decarboxylase deficiency | Pharmacological therapy | Dopamine agonist, monoamine oxidase (MAO) inhibitors, L-dopa + carbidopa (depending on mutation) | 4 | E, G | |
Vitamin & trace element | Pyridoxine, folinic acid ± | 4 | E, G | ||
Gene-based therapy | Gene therapy | 4 | A, B, E | ||
Arylsulfatase A deficiency | Gene-based therapy | OTL-200 (stem cell-based gene therapy) | 2c | A, E | |
Stem cell therapy | Hematopoietic stem cell transplantation | 4 to 5 | D | ||
Aspartylglucosaminidase deficiency | Stem cell therapy | Hematopoietic stem cell transplantation | 4 to 5 | D | [78] |
ATP-sensitive potassium channel regulatory/pore-forming subunit superactivity | Pharmacological therapy | Sulfonylurea | 4 | A, B, E, G | |
Autosomal recessive GTP cyclohydrolase 1 deficiency | Nutritional therapy | Phenylalanine-reduced diet ± | 4 | D, E | [62] |
Vitamin & trace element | Folinic acid ± | 4 | A, E, F | [62] | |
Pharmacological therapy | L-dopa + carbidopa, 5-Hydroxytryptophan, sapropterin dihydrochloride (synthetic BH4) co-factor therapy | 4, 4 to 5 for 5-Hydroxytryptophan | A, B, E, F, G | [62] | |
Beta-glucuronidase deficiency (synonym: Sly syndrome) | Enzyme replacement therapy | Vestronidase | 4 | A, G | [81] |
Stem cell therapy | Hematopoietic stem cell transplantation | 4 | D, G | ||
Biotinidase deficiency | Vitamin & trace element | Biotin | 2c | A, E, G | [82] |
Branched-chain ketoacid dehydrogenase E1 alpha (BCKDHA)/beta (BCKDHB)/E2 (DBT) deficiency (synonym: maple syrup urine disease type 1a (BCKDHA)/2 (DBT); Dihydrolipoyl transacylase deficiency (DBT)) | Nutritional therapy | Restriction of branched chain amino acids, isoleucine, valine, avoid fasting, sick day management | 4 | A, C, D, G | |
Vitamin & trace element | Thiamine ± | 4 | C, D, G | ||
Other | Hemodialysis, peritoneal dialysis | 4 | D | ||
Solid organ transplant | Liver transplantation | 4 | C, D, G | ||
Branched-chain ketoacid dehydrogenase kinase deficiency | Nutritional therapy | Branched-chain amino acid supplementation | 5 | A, B, G | [85] |
CAD trifunctional protein deficiency | Pharmacological therapy | Uridine | 4 | A, F | [30] |
Carbamoyl phosphate synthetase 1 deficiency | Nutritional therapy | Protein defined diet, arginine or citrulline | 2b, effect on growth 4 | B, C, D, E, G | [72] |
Pharmacological therapy | Sodium phenylbutyrate, glycerol phenylbutyrate, sodium benzoate, N-carbamyl-L-glutamate (carglumic acid) | 2b, 4 to 5 for carglumic acid | B, C, D, E, D for carglumic acid | [72] | |
Other | Hemodialysis, peritoneal dialysis | 4 | D | [72] | |
Solid organ transplant | Liver transplantation | 4 | A, B, D, E | [72] | |
Carbonic anhydrase VA deficiency | Nutritional therapy | Sick day management | 4 | C, D | [86] |
Pharmacological therapy | N-carbamyl-L-glutamate (carglumic acid) | 4 | C, D | [86] | |
Citrin deficiency | Nutritional therapy | High-protein/high-fat/low-carbohydrate diet, avoid fasting, avoid glucose iv, lactose restriction, medium -chain triglycerides | 4 | B, C, D, E, F, G | [87] |
Other | Hemodialysis, peritoneal dialysis | 4 | D | [87] | |
Solid organ transplant | Liver Transplantation | 4 | C | [87] | |
CLN7 disease | Gene based therapy | (Intrathecal) milasen | 4 to 5 | F | [36] |
Coenzyme Q5 methyltransferase deficiency | Vitamin & trace element | CoQ10 | 4 to 5 | A, B, E | [88] |
Coenzyme Q8A (ADCK3) deficiency | Vitamin & trace element | CoQ10 | 4 to 5 | E | [89] |
Copper-transporting ATPase subunit alpha deficiency (synonyms: Menkes disease [severe]; occipital horn syndrome [milder]) | Pharmacological therapy | Copper histidine | 4 | D | [90] |
Copper-transporting ATPase subunit beta deficiency (synonym: Wilson disease) | Vitamin & trace element | Zinc | 4 | A, E, G | |
Pharmacological therapy | Copper chelators, tetrathiomolybdate | 4, 1b for tetrathiomolybdate | A, E, G | ||
Creatine transporter deficiency | Nutritional therapy | Creatine, glycine, arginine | 4 | A, F | [93] |
Cyclic pyranopterin monophosphate synthase deficiency (synonym: molybdenum cofactor deficiency type A) | Pharmacological therapy | Cyclic pyranopterin monophosphate | 2b | A, F | [94] |
Cystathionine beta-synthase deficiency (synonym: classic homocystinuria) | Nutritional therapy | Protein defined diet, methionine restriction | 2c | C, D, G | [95] |
Vitamin & trace element | Pyridoxine, betaine | 2c | D, E, G | [95] | |
Dihydrofolate reductase deficiency | Vitamin & trace element | Folic acid | 4 | F, G | [96] |
Dihydropteridine reductase deficiency | Nutritional therapy | Phenylalanine-reduced diet | 4 | D, E | [62] |
Vitamin & trace element | Folinic acid | 4 | A, E, F | [62] | |
Pharmacological therapy | L-dopa + carbidopa, 5-Hydroxytryptophan, sapropterin dihydrochloride (synthetic BH4) co-factor therapy ± | 4 | A, B, E, F, G | [62] | |
DNAJC12 deficiency | Pharmacological therapy | BH4, L-dopa + carbidopa ± , 5-hydroxytryptophan ± | 4 | A, D, E | [97] |
Electron transfer flavoprotein subunit alpha (ETFA)/subunit beta (ETFB)/dehydrogenase deficiency (ETFDH) (synonym: glutaric acidemia type 2A/2B/2C; multiple acyl-CoA dehydrogenase deficiency type 2A/2B/2C) | Nutritional therapy | Carnitine | 5 | C, D | [98] |
Vitamin & trace element | Riboflavin | 5 | C, D | [98] | |
Nutritional therapy | Beta-hydroxybutyrate | 2c | E, G | [98] | |
Epsilon-N-trimethyllysine hydroxylase deficiency | Nutritional therapy | Carnitine | 4 to 5 | A, B, C | [99] |
Folate receptor alpha deficiency (synonym: neurodegeneration due to cerebral folate transport deficiency) | Vitamin & trace element | Folinic acid | 4 | A, D, E, F | [100] |
GLUT1 deficiency | Nutritional therapy | Ketogenic diet | 4 | F | [101] |
Pharmacological therapy | Triheptanoin | 2b | A, E | [102] | |
Glutamine synthetase deficiency | Nutritional therapy | Glutamine | 4 to 5 | A, E | [103] |
Glutaryl-CoA dehydrogenase deficiency (synonym: glutaric aciduria type 1) | Nutritional therapy | Protein defined diet, lysine restriction, carnitine | 2c | C, D, E, G | [44] |
Glycine encephalopathy due to aminomethyltransferase (AMT) or glycine decarboxylase (GLDC) deficiency (synonym: nonketotic hyperglycinemia) | Pharmacological therapy | Sodium benzoate, N-nitrosodimethylamine receptor antagonists | 4 | B, D, E, F | [104] |
Guanidinoacetate methyltransferase deficiency | Nutritional therapy | Arginine restriction, creatine and ornithine | 4 | B, D, E, F | [105] |
Hereditary ceruloplasmin deficiency | Other | Iron chelation | 4 | D, E | [106] |
Holocarboxylase synthetase deficiency | Vitamin & trace element | Biotin | 4 | D | [107] |
Homocystinuria, cblDv1 type | Vitamin & trace element | Hydroxycobalamin, betaine ± | 4 | C, D, G | [61] |
Iduronate sulfatase deficiency (synonym: Hunter syndrome) | Stem cell therapy | Hematopoietic stem cell transplantation | 4 | D, E, G | [108] |
Ionotropic glutamate receptor NMDA type subunit 1 dysregulation | Pharmacological therapy | Memantine | 4 to 5 | A, F | [109] |
Ionotropic glutamate receptor NMDA type subunit 2A dysregulation | Pharmacological therapy | Memantine, IVIG | 4 | F | |
Ionotropic glutamate receptor NMDA type subunit 2B dysregulation | Nutritional therapy | L-serine (for loss-of-function mutations) | 4 to 5 | A | [112] |
Ionotropic glutamate receptor NMDA type subunit 2D superactivity | Pharmacological therapy | Memantine, IVIG | 4 | A, F | |
Isoleucyl-tRNA synthetase 1 deficiency | Nutritional therapy | L-isoleucine, natural protein fortification | 4 to 5 | A, E, G | |
Isovaleryl-CoA dehydrogenase deficiency (synonym: isovaleric acidemia) | Nutritional therapy | Protein defined diet, carnitine, avoid fasting, sick day management | 2c | C, G | [116] |
Pharmacological therapy | N-carbamyl-L-glutamate (carglumic acid) | 4 | C, G | [116] | |
Leucyl-tRNA synthetase 1 deficiency | Nutritional therapy | L-leucine, natural protein fortification | 4 to 5 | A, E, G | |
MEDNIK syndrome | Vitamin & trace element | Zinc acetate | 4 to 5 | A, B, G | [117] |
Methionine synthase deficiency (synonym: homocystinuria-megaloblastic anemia, cblG type) | Vitamin & trace element | Hydroxycobalamin, betaine ± | 4, 5 for betaine | C, D, G | [61] |
Methionine synthase reductase deficiency (synonym: homocystinuria-megaloblastic anemia, cblE type) | Vitamin & trace element | Hydroxycobalamin, betaine ± | 4, 5 for betaine | C, D, G | [61] |
Methionyl-tRNA synthetase 1 deficiency | Nutritional therapy | Methionine, increase protein intake | 5 | A, G | [118] |
Methylmalonic aciduria and homocystinuria, cblC type | Nutritional therapy | Carnitine ± | 5 | C, D, G | [61] |
Vitamin & trace element | Hydroxycobalamin, betaine | 4 | C, D, G | [61] | |
Methylmalonic aciduria and homocystinuria, cblD type | Nutritional therapy | Carnitine ± | 5 | A, D, G | [61] |
Vitamin & trace element | Hydroxycobalamin, betaine ± | 4 to 5, 5 for betaine | A, D, G | [61] | |
Methylmalonic aciduria and homocystinuria, cblF type | Vitamin & trace element | Hydroxycobalamin, betaine | 4 | D, G | [61] |
Methylmalonic aciduria and homocystinuria, cblJ type | Vitamin & trace element | Hydroxycobalamin, betaine ± | 4 to 5, 5 for betaine | D, G | [119] |
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | Nutritional therapy | Protein defined diet, carnitine, avoid fasting, sick day management | 2c | C, D, G | [120] |
Pharmacological therapy | N-carbamyl-L-glutamate (carglumic acid), sodium benzoate, antibiotics | 4 | C, D, G | [120] | |
Other | Hemodialysis, peritoneal dialysis | 4 | D | [120] | |
Solid organ transplant | Liver and/or kidney transplantation | 4 | C, D, G | [120] | |
Methylmalonic aciduria, cblA type | Nutritional therapy | Protein defined diet, carnitine, avoid fasting, sick day management | 4 | C, D, G | [120] |
Vitamin & trace element | Hydroxycobalamin | 4 | C, D, G | [120] | |
Pharmacological therapy | N-carbamyl-L-glutamate (carglumic acid), sodium benzoate, antibiotics | 4 | D | [120] | |
Other | Hemodialysis, peritoneal dialysis | 4 | D | [120] | |
Solid organ transplant | Liver transplantation and/or kidney transplantation | 4 | C, D, G | [120] | |
Methylmalonic aciduria, cblB type | Nutritional therapy | Protein defined diet, carnitine, avoid fasting, sick day management | 4 | C, D, G | [120] |
Vitamin & trace element | Hydroxycobalamin | 4 | C, D, G | [120] | |
Pharmacological therapy | N-carbamyl-L-glutamate (carglumic acid), sodium benzoate, antibiotics | 4 | D | [120] | |
Other | Hemodialysis, peritoneal dialysis | 4 | D | [120] | |
Solid organ transplant | Liver transplantation and/or kidney transplantation | 4 | C, D, G | [120] | |
Methylmalonic aciduria, cblDv2 type | Nutritional therapy | Protein defined diet, carnitine, avoid fasting, sick day management | 4 | C, D, G | [120] |
Vitamin & trace element | Hydroxycobalamin | 4 | C, D, G | [120] | |
Pharmacological therapy | N-carbamyl-L-glutamate (carglumic acid), sodium benzoate, antibiotics | 4 | D | [120] | |
Other | Hemodialysis, peritoneal dialysis | 4 | D | [120] | |
Solid organ transplant | Liver transplantation and/or kidney transplantation | 4 | C, D, G | [120] | |
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency | Nutritional therapy | Avoid Fasting, sick day management, dietary precursor restriction ± | 5 | C | [121] |
Mitochondrial acetoacetyl-CoA thiolase deficiency | Nutritional therapy | Avoid fasting, sick day management, protein restriction, isoleucine restriction | 5 | C | [122] |
Mitochondrial aspartate aminotransferase deficiency | Nutritional therapy | L-serine | 4 | A | [123] |
Vitamin & trace element | Pyridoxine | 4 | A, F | [123] | |
Mitochondrial aspartate-glutamate carrier isoform 1 deficiency (synonym: aralar deficiency) | Nutritional therapy | Ketogenic diet | 4 | A, E, F | [124] |
Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MT-ND1/MT-ND4/MT-ND5/MT-ND6/MT-CO1/MT-CPO2/MT-CO3/ MT-TQ/MT-TH/MT-TL1/MT-TF/MT-TS1/MT-TS2/MT-TW) | Nutritional therapy | Arginine, citrulline, taurine | 4 to 5, 2b for Taurine | C, D, E, F | |
Mitochondrial ornithine transporter deficiency (synonym: hyperornithinemia-hyperammonemia-homocitrullinuria syndrome) | Nutritional therapy | Protein defined diet, arginine or citrulline | 2b, effect on growth 4 | B, C, D, E, G | [72] |
Pharmacological therapy | Sodium phenylbutyrate, glycerol phenylbutyrate, sodium benzoate | 2b | B, C, D, E | [72] | |
Other | Hemodialysis, peritoneal dialysis | 4 | D | [72] | |
Solid organ transplant | Liver transplantation | 4 to 5 | A, B, D, E, systemic phenotype persists | [72] | |
Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency | Nutritional therapy | Valine restriction | 4 | A, E, G | [58] |
Mitochondrial sulfur dioxygenase deficiency (synonym: ethylmalonic encephalopathy) | Pharmacological therapy | N-acetylcysteine, antibiotics | 4 | E, G | [127] |
Solid organ transplant | Liver transplantation | 4 | A | [127] | |
Mitochondrial thiamine pyrophosphate transporter deficiency | Vitamin & trace element | Thiamine | 4 | C, D | [128] |
N-acetylglutamate synthase deficiency | Nutritional therapy | Protein defined diet, arginine or citrulline | 2b, effect on growth 4 | B, C, D, E, G | [72] |
Pharmacological therapy | Sodium phenylbutyrate, glycerol phenylbutyrate, sodium benzoate, N-carbamyl-L-glutamate (carglumic acid) | 2b, 4 for carglumic acid | B, C, D, E, D for carglumic acid | [72] | |
Other | Hemodialysis, peritoneal dialysis | 4 | D | [72] | |
Solid organ transplant | Liver transplantation | 4 | A, B, D, E | [72] | |
NAD(P)HX epimerase deficiency | Vitamin & trace element | Niacin, CoQ10 | 4 to 5 | A, G | [129] |
Niemann-Pick disease type C1 (NPC1)/C2 (NPC2) | Pharmacological therapy | Miglustat, intrathecal 2-hydroxypropyl-β-cyclodextrin | 1b, 2b for 2-hydroxypropyl-β-cyclodextrin | D, E | |
NRF2 superactivity (synonym: immunodeficiency, developmental delay, and hypohomocysteinemia) | Vitamin & trace element | Ascorbic acid | 4 to 5 | A | [132] |
Pharmacological therapy | Luteolin | 4 to 5 | A | [132] | |
Ornithine transcarbamylase deficiency | Nutritional therapy | Protein defined diet, arginine or citrulline | 2b, effect on growth 4 | B, C, D, E, G | [72] |
Pharmacological therapy | Sodium phenylbutyrate, glycerol phenylbutyrate, sodium benzoate | 2b | B, C, D, E | [72] | |
Other | Hemodialysis, peritoneal dialysis | 4 | D | [72] | |
Solid organ transplant | Liver transplantation | 4 | A, B, D, E | [72] | |
Phenylalanine hydroxylase deficiency (synonym: phenylketonuria) | Nutritional therapy | Protein defined diet, phenylalanine-free L-amino acid suppletion/Glycomacropeptide (GMP), large neutral amino acid (LNAA), fatty acids | 2a, GMP 4 | B, D, E | [43] |
Pharmacological therapy | Sapropterin dihydrochloride (synthetic BH4) co-factor therapy | 1b | B, D, E | [43] | |
Enzyme replacement therapy | Pegvaliase | 1b | B, D, E | [43] | |
Phenylalanyl-tRNA synthetase subunit beta deficiency | Nutritional therapy | L-phenylalanine | 4 to 5 | A, G | [115] |
Phosphoribosylpyrophosphate synthetase deficiency | Pharmacological therapy | S-adenosylmethionine | 4 | D, G | [133] |
Phosphoserine aminotransferase deficiency | Nutritional therapy | L-Serine, glycine | 4 | D, E, F | [59] |
Phosphoserine phosphatase deficiency | Nutritional therapy | L-Serine, glycine | 4 | D, E, F | [59] |
PIGA-CDG | Nutritional therapy | Ketogenic diet | 4 | A, F | [134] |
PIGM-CDG | Pharmacological therapy | Sodium phenylbutyrate | 4 | A, F | [134] |
PIGO-CDG | Vitamin & trace element | Pyridoxine | 4 to 5 | F | [134] |
PMM2-CDG | Pharmacological therapy | Acetazolamide | 1b | E, G | [135] |
Propionic acidemia due to propionyl-CoA carboxylase subunit alpha (PCCA)/beta (PCCB) deficiency | Nutritional therapy | Protein defined diet, carnitine, avoid fasting, sick day management | 2c | C, D, G | [120] |
Pharmacological therapy | N-carbamyl-L-glutamate (carglumic acid), sodium benzoate, antibiotics | 4 | C, D, G | [120] | |
Other | Hemodialysis, peritoneal dialysis | 4 | D | [120] | |
Solid organ transplant | Liver and/or kidney transplantation | 4 | C, D, G | [120] | |
Proton-coupled folate transporter deficiency (synonym: hereditary folate malabsorption) | Vitamin & trace element | (Levo-)folinic acid | 4 | A, E, F, G | [136] |
Pyridoxamine 5′-phosphate oxidase deficiency | Vitamin & trace element | Pyridoxal phosphate | 4 | D, E, F | [137] |
Pyruvate dehydrogenase E1 alpha (PDHA1)/beta (PDHB)/E2 (DLAT)/E3 (DLD)/E3BP (PDHX) deficiency | Nutritional therapy | Ketogenic diet | 4 for PDHA1 and PDHX, 5 for other genes | A, D, E, F | |
Vitamin & trace element | Thiamine | 4 for some mutations | D, E, F | ||
Pyruvate dehydrogenase phosphatase deficiency | Nutritional therapy | Ketogenic diet, thiamine ± | 4 | A, D, E | [140] |
S-adenosylhomocysteine hydrolase deficiency | Nutritional therapy | Methionine restriction, creatinine, phosphatidylcholine | 4 | A, E, G | [141] |
Solid organ transplant | Liver transplantation | 4 to 5 | A, E, G | [141] | |
Sepiapterin reductase deficiency | Pharmacological therapy | L-dopa + carbidopa, 5-Hydroxytryptophan | 4 | A, B, E, F, G | [62] |
Vitamin & trace element | Folinic acid ± | 5 | A, E, F | [62] | |
Seryl-tRNA synthetase 1 deficiency | Nutritional therapy | L-serine | 4 to 5 | A, B, G | |
SLC35A2-CDG | Nutritional therapy | Galactose | 4 | E, F, G | [142] |
SLC35C1-CDG | Nutritional therapy | Fucose | 4 | A, G | [134] |
SLC39A8 deficiency | Nutritional therapy | Galactose, manganese, uridine | 4 | F | [134] |
Sodium-dependent multivitamin transporter deficiency | Vitamin & trace element | Biotin, alpha-lipoic acid, pantothenic acid | 4 | A, D, G | [143] |
Sterol 27-hydroxylase deficiency (synonym: cerebrotendinous xanthomatosis) | Pharmacological therapy | Chenodeoxycholic Acid | 3a | B, D, E, G | [144] |
Succinic semialdehyde dehydrogenase deficiency | Pharmacological therapy | Vigabatrin | 4 | B, F | [145] |
Thiamine pyrophosphokinase deficiency | Vitamin & trace element | Thiamine | 4 | D | [146] |
Thiamine transporter 2 deficiency (synonym: biotin-thiamine-responsive basal ganglia disease) | Vitamin & trace element | Thiamine, biotin | 2c for thiamine, 4 for biotin | D | [147] |
Transcobalamin II deficiency | Vitamin & trace element | Cyanocobalamin, hydroxycobalamin | 4 | D, E, G | [148] |
Tripeptidyl-peptidase 1 deficiency (synonym: CLN2 disease) | Enzyme replacement therapy | Cerliponase alfa | 2b | D | [149] |
Tyrosine aminotransferase deficiency (synonyms: tyrosinemia type 2; Richner-Hanhart syndrome) | Nutritional therapy | Protein defined diet, phenylalanine and tyrosine restriction | 4 G, 5 for D | D, G | [150] |
Tyrosine hydroxylase deficiency | Pharmacological therapy | L-dopa + carbidopa | 4 | A, E | [151] |
Vesicular monoamine transporter 2 deficiency | Pharmacological therapy | Pramipexol (dopamine agonist) | 4 | A, E | [152] |
X-linked adrenoleukodystrophy | Gene-based therapy | Gene therapy | 5 | D, E | [153] |
Stem cell therapy | Hematopoietic stem cell transplantation | 1c | D, E | [154] |