Biochemical category | Disease name | OMIM# | Gene(s) | Treatment | Effect | Level of evidence | CP symptoms |
---|---|---|---|---|---|---|---|
Amino acids | Hartnup disease | 234500 | SLC6A19 (AR) | High protein diet | Stabilizing/preventative treatment | 4-5 | Dystonia |
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome | 238970 | SLC25A15 (AR) | Dietary protein restriction, ornithine supplement, sodium benzoate, phenylacetate | Stabilizing/preventative treatment | 4 | Spasticity | |
Late onset non-ketotic hyperglycinemia | 605899 | AMT/GLDC/GCSH (AR) | Glycine restriction, +/− sodium benzoate, NMDA receptor antagonists, other neuromodulating agents | Stabilizing/preventative treatment | 4-5 | Spastic diplegia | |
Phenylketonuria (PKU) | 261600 | PAH (AR) | Dietary phenylalanine restriction +/− amino acid supplements (BH(4) supplement) | Stabilizing/preventative treatment | 2a (4) | Spastic diplegia | |
PHGDH deficiency (Serine deficiency) | 601815 | PHGDH (AR) | L-serine & +/−glycine supplements | Primary/targeting underlying pathophysiology | 4 | Spastic diplegia/tetraparesis | |
Cerebral glucose transport | Blood brain-barrier glucose-transporter (GLUT1) defect | 606777 | SLC2A1 (AR) | Ketogenic diet | Primary/targeting underlying pathophysiology | 4 | Spasticity, dystonia, ataxia |
Creatine | GAMT deficiency | 612736 | GAMT (AR) | Arginine restriction, creatine & ornithine supplements | Primary/targeting underlying pathophysiology | 4 | Movement disorder: extrapyramidal signs, athetosis, & ataxia |
Fatty acid oxidation | Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency | 201450 | ACADM (AR) | Emergency regimen, L-carnitine, avoid fasting | Stabilizing/preventative treatment | 2a | CP symptoms |
Short-chain acyl-CoA dehydrogenase (SCAD) deficiency | 201470 | ACADS (AR) | Emergency regimen, L-carnitine | Stabilizing/preventative treatment | 2c | Spastic diplegia | |
Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency | 201475 | ACADVL (AR) | Avoidance of fasting, low-fat diet, Medium Chain Triglyceride oild | Stabilizing/preventative treatment | 4 | Neonatal asphyxia | |
Hyperhomo-cysteinemia | Homocystinuria due to Cystathionine β-synthase deficiency | 236200 | CBS (AR) | Methionine restriction, +/− pyridoxine, +/− betaine | Stabilizing/preventative treatment | 2c | Dystonia |
MTHFR deficiency | 236250 | MTHFR (AR) | Betaine supplements, +/− folate, carnitine, methionine supplements | Stabilizing/preventative treatment | 4 | Ataxic gait, hypotonia, extrapyramidal movements, upper motor neuron signs | |
Lipids | Abetalipoproteinemia | 200100 | MTTP (AR) | Low long-chain fatty acid diet with fat-soluble vitamin (i.e., A, D, E, K) supplementation | Primary/targeting underlying pathophysiology | 4 | Ataxia, abnormal gait |
Lysosomal | Fucosidosis | 230000 | FUCA1 (AR) | Haematopoietic stem cell transplant | Stabilizing/preventative treatment | 5 | Severe spasticity; spastic paresis, generalized dystonia |
Krabbe disease | 245200 | GALC (AR) | Haematopoietic stem cell transplant | Stabilizing/preventative treatment | 2c | Progressive spasticity | |
Metachromatic leucodystrophy (MLD) | 250100 | ARSA (AR) | Haematopoietic stem cell transplant | Stabilizing/preventative treatment | 4-5 | Loss of all gross motor function measured by CP scale; ataxia | |
Neimann-Pick, type C | 257220 | NPC1, NPC2 | Miglustat | Stabilizing/preventative treatment | 1b | Axial hypotonia, spastic diparesis, dystonic posturing of the hands | |
Metals | Menkes Disease | 309400 | ATP7A | Copper histidine | Stabilizing/preventative treatment | 4 | Progressive spasticity, hypotonia |
Wilson Disease | 277900 | ATP7B | Zinc & tetrathiomolybdate; oxcarbazepine | Stabilizing/preventative treatment | 1b | Neurological symptoms, dystonia | |
Mitochondria | Coenzyme Q10 deficiency | 607426 | COQ2, APTX, PDSS1, PDSS2, CABC1, COQ9 (most AR) | CoQ supplements | Primary/targeting underlying pathophysiology | 4 | Spastic paresis; progressive ataxia and dystonia |
MELAS | 540000 | mt.A3243G, mt.G13513A (mtDNA) | Arginine supplements | Stabilizing/preventative treatment | 4-5 | dx. CP | |
Pyruvate dehydrogenase deficiency | 312170, 245348 | PDHA1 (X-linked recessive), DLAT (AR), PDHX (AR) | Ketogenic diet & thiamine | Primary/targeting underlying pathophysiology | 4 | Spastic quadriplegia; dystonia | |
Neurotransmission | Aromatic-L-amino-acid decarboxylase deficiency | 608643 | DDC (AR) | MAO inhibitors, B6, anti-cholinergics, dopa agonists) | Primary/targeting underlying pathophysiology | 4 | Limb dystonia, athetoid movement |
DHPR deficiency (biopterin deficiency) | 261630 | QDPR (AR) | BH4, diet, amine replacement, folinic acid | Primary/targeting underlying pathophysiology | 4 | Ataxia, gait disorder, peripheral spasticity | |
Dopamine transporter deficiency syndrome | 126455 | SLC6A3 | Dopamine antagonist (Ropinirole) | Primary/targeting underlying pathophysiology | 4 | dx. CP | |
GTPCH1-deficient dopa-responsive dystonia (aka Segawa’s disease) | 233910 | GCH1 (AR) | BH4, amine replacement | Primary/targeting underlying pathophysiology | 4 | dx. CP; spastic diplegia | |
PTPS deficiency (biopterin deficiency) | 261640 | PTS (AR) | BH4, diet, amine replacement | Primary/targeting underlying pathophysiology | 4 | Dystonia; spastic extremities; generalized dystonia, choreoathetoid arm movements & axial hypotonia | |
Sepiapterin reductase deficiency | 612716 | SPR (AR) | Amine replacement | Primary/targeting underlying pathophysiology | 4 | Limb spasticity, dystonic signs; “hypotonic cerebral palsy”; dystonia, axial hypotonia; misdx. CP | |
Succinic semialdehyde dehydrogenase deficiency (SSADH) | 271980 | ALDH5A1 (AR) | Vigabatrin | Stabilizing/preventative treatment | 4 | Hypotonia, ataxia; gait clumsiness, dystonia | |
Tyrosine hydroxylase deficiency | 605407 | TH (AR) | L-dopa substitution | Primary/targeting underlying pathophysiology | 4 | Spastic paraplegia/tetraparesis | |
Vesicular monoamine transporter 2 (VMAT2) | 193001 | SLC18A2 | Dopamine aginist | Primary/targeting underlying pathophysiology | 4 | Dystonia | |
Organic acids | β-Ketothiolase deficiency | 203750 | ACAT1 (AR) | Avoid fasting, emergency regimen, protein restriction | Stabilizing/preventative treatment | 5 | Ataxia, diplegia, hypotonia |
2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency | 300438 | HSD17B10 (X-linked) | Avoid fasting, emergency regimen, isoleucine restricted diet | Stabilizing/preventative treatment | 5 | Ataxia, dystonia, choreoathetosis, spastic di-/tetra-plegia, hypotonia | |
3-Methylcrotonyl-CoA carboxylase (MCC) deficiency | 210200; 210210 | MCC1/MCC2 (AR) | Dietary protein restriction; carnitine, glycine, biotin supplements; avoid fasting; emergency regimen | Stabilizing/preventative treatment | 5 | dx. CP | |
3-Methylglutaconic aciduria type 1 | 250950 | AUH (AR) | Carnitine supplements, avoid fasting, emergency regimen | Stabilizing/preventative treatment | 5 | dx. CP | |
Ethylmalonic encephalopathy | 602473 | ETHE1 (AR) | N-acetylcysteine, oral metronidazol | Stabilizing/preventative treatment | 4 | CNS malformations, episodic ataxia; pyramidal tract signs | |
Glutaric aciduria type I (GA1) aka glutaryl-CoA dehydrogenase deficiency | 231670 | GCDH (AR) | Lysine restriction, carnitine supplements | Stabilizing/preventative treatment | 2a | Generalized spasticity, dystonia with athethosis; dx. CP; dyskinesia, dystonic tetraparesis | |
Isovaleric acidemia | 243500 | IVD (AR) | Dietary protein restriction, carnitine supplements, avoid fasting, emergency regimen | Stabilizing/preventative treatment | 2c | Hypotonia, paresis | |
Multiple acyl-CoA-dehydrogenase deficiency (MADD) (aka Glutaric aciduria type II) | 231680 | ETFA, ETFB, ETFDH (AR) | Carnitine, riboflavin, β-hydroxybutyrate supplements; emergency regimen | Primary/targeting underlying pathophysiology | 5 | Encephalopathy | |
Maple syrup urine disease | 248600 | DBT, BCKDHB, BCKDHA (AR) | Dietary restriction, branched amino-acids, avoid fasting, (liver transplantation) | Stabilizing/preventative treatment (liver tx = primary treatment) | 4 (4) | Spastic diplegic CP; paroxysmal dystonia; ataxia | |
Methylmalonic acidemia (mutase deficiency) | 251000 | MUT (AR) | Dietary protein restriction, carnitine supplements, avoid fasting, emergency regimen | Stabilizing/preventative treatment | 2c | Total body dystonia | |
Lesch-Nyhan syndrome | 300322 | HPRT1 (X-linked) | Haematopoietic stem cell transplant | Primary/targeting underlying pathophysiology | 4-5 | dx. Athetotic/dyskinetic CP; dystonia | |
Propionic acidemia | 606054 | PCCA, PCCB (AR) | Dietary protein restriction, carnitine supplements, avoid fasting, emergency regimen | Stabilizing/preventative treatment | 2c | Dystonia, hypotonia | |
Urea cycle | Argininemia | 207800 | ARG1 (AR) | Dietary protein restriction, arginine supplement, sodium benzoate, phenylbutyrate (Liver transplantation) | Stabilizing/preventative treatment (liver tx = primary treatment) | 2b (4) | Spastic diplegia, ataxia, dx. CP |
Argininosuccinic aciduria | 207900 | ASL (AR) | Low protein diet, arginine-supplements, sodium benzoate, phenylbutyrate (liver transplantation) | Stabilizing/preventative treatment (liver tx = primary treatment) | 2b (4) | Cerebellar ataxia | |
Citrullinemia, type II | 605814 | SLC25A13 (AR) | Dietary protein restriction, arginine supplement, sodium benzoate, phenylbutyrate (Liver transplantation) | Stabilizing/preventative treatment (liver tx = primary treatment) | 2b (4) | dx. CP; spastic quadriplegia | |
Ornithine transcarbamylase deficiency | 311250 | OTC (X-linked) | Dietary protein restriction, citrulline supplements, sodium benzoate/phenylbutyrate (Liver transplantation) | Stabilizing/preventative treatment (liver tx = primary treatment) | 2b (4) | Hemiplegia; ataxia; gait disturbance | |
Vitamins/Co-factors | Biotinidase deficiency | 2532760 | BTD (AR) | Biotin supplement | Primary/targeting underlying pathophysiology | 2c | Spastic tetraparesis |
Biotin-thiamine-responsive basal ganglia disease | 607483 | SLC19A3 (AR) | Biotin supplement | Primary/targeting underlying pathophysiology | 4 | Ataxia, dystonia | |
Cerebral folate deficiency syndrome | 613068 | FOLR1 (AR) | Folinic acid | Primary/targeting underlying pathophysiology | 4 | spastic paraplegia; perinatal asphyxia | |
Holocarboxylase synthetase deficiency | 253270 | HLCS (AR) | Biotin supplement | Primary/targeting underlying pathophysiology | 4 | dx. CP | |
Hypermanganesemia with dystonia, polycythemia, and cirrhosis (HMDPC) | 613280 | SLC30A10 (AR) | Chelation therapy | Primary/targeting underlying pathophysiology | 4 | Dystonia | |
Molybdenum cofactor deficiency | 252150 | MOCS1, MOCS2, (AR) | Precursor Z/cPMP | Primary/targeting underlying pathophysiology | 4 | Spastic quadriplegia dx. CP | |
Pyridoxamine 5’-phosphate oxidase deficiency | 610090 | PNPO (AR) | Pyridoxal 5’-phosphate | Stabilizing/preventative treatment | 4 | Spastic quadriplegia |