1
Supplementary Table 1 Proposed treatments in adult neurometabolic diseases.1
Treatments
Vitamins
B1 (thiamine)
B6
Diseases
Recommended dose
Route
Adverse effects
Pyruvate dehydrogenase deficiency
Cystathionine  synthase deficiency
500–1000 mg/day
250–500 mg/day
Oral
Oral
B9 (folinic acid)
Intracerebral folate deficiency, MTHFR
deficiency, dyhydropteridine reductase
deficiency
CblC disease, MTHFR deficiency
0.5–1 mg/kg/day (intracerebral folate
deficiency), 25 mg/day (MTHFR and
dyhydropteridine reductase deficiencies)
Oral: 1 mg/day, intramuscular: 1 mg/day
initially, then 1 mg/week or 1 mg/month.
Oral
Not reported
Polyneuropathy
with doses >1000
mg/d
Epilepsy with
doses
>1mg/kg/day
Not reported
B12 (cobalamin)
H (biotin)
Vitamin E
Vitamin cocktail
Cofactors
BH4
Betaine
Carbaglu
Neurotransmitters
Intramuscular
(CblC disease)
or oral
Oral
Not reported
Biotinidase deficiency, biotin-responsive 10–20 mg/day (biotinidase deficiency and
encephalopathy, biotin responsive basal biotin responsive encephalopathy); 0.5
ganglia disease
mg/kg/day (biotin responsive basal ganglia
disease)
Tocopherol binding protein deficiency,
10–100 mg/kg/day
Oral
abetalipoproteinemia,
hypobetalipoproteinemia
Can be tried in an unexplained
Doses per day: biotin 10 mg, thiamine 500 Oral
neurological disease (3-month trial)
mg, riboflavin 300 mg, vitamin B6 500
mg, folinic acid 25 mg
PTP synthase deficiency
CblC disease, MTHFR deficiency,
cystathionine  synthase deficiency
N-acetylglutamate synthetase deficiency
Not reported
Not reported
1–3 mg/kg/day
6–9 g/day
Oral
Oral
Not reported
Not reported
50 mg/kg/day in four divided doses
Oral or
intravenous
Not reported
2
Levodopa
5-hydroxytryptophan
Amino acids
L-serine
L-arginine
L-citrulline
Specific diets
Low phytanic acid
GTP cyclohydrolase 1 deficiency,
tyrosine hydroxylase deficiency, PTP
synthase deficiency, sepiapterin
reductase deficiency, dyhydropteridine
reductase deficiency
PTP synthase deficiency, sepiapterin
reductase deficiency, dyhydropteridine
reductase deficiency
150–600 mg/day in three or four divided
doses
Oral
Dyskinesias
300–600 mg/day in three divided doses
Oral
Nausea, diarrhoea,
tachycardia,
anorexia
Serine deficiency
200–400 mg/kg/day
Urea cycle disorders, Triple H syndrome 100 mg/kg/day (OTC and CPS
deficiencies), up to 700mg/kg/day in ASS
deficiency
Triple H syndrome, OTC deficiency,
3.8 g/m2/day
CPS deficiency
Oral
Oral or
intravenous
Not reported
Not reported
Oral
Not reported
Refsum disease
NA
Not reported
NA
Not reported
Calories intake subdivided into: lipids 70–
80%, glucose 5–10%, proteins 15–20%
Proteins <1.5 g/kg/day
NA
Not reported
NA
Not reported
300–900 mg/day (increase progressively)
Oral
Long chain fatty acids Trifunctional protein deficiency
restriction
Ketogenic
Pyruvate dehydrogenase deficiency,
Glut1 deficiency
Protein restriction
Phenylketonuria, urea cycle disorders,
organic acidurias, triple H syndrome,
leucinosis
Chelators
D-penicillamine
Wilson disease
Phytanate intake between 10 and 20
mg/day
Triethylene tetramine
(trientine)
Zinc sulphate
Wilson disease
600–2.4 g/day
Oral
Initial worsening
of symptoms,
lupus, nephropathy
Not reported
Wilson disease
Oral
Not reported
Sodium benzoate
Nonketotic hyperglycinemia, urea cycle
600 mg/day initially, then 300 mg/day
(maintenance dose)
250 mg/kg/day in divided doses
Oral or
Not reported
3
disorders
Sodium
Urea cycle disorders
phenylbutyrate
Bioenergetic molecules
Ubiquinone
Coenzyme Q10 deficiency
L-carnitine
Organic acidurias
Enzymes
Imiglucerase
Gaucher disease
Agalsidase alpha
Fabry disease
(Replagal)
Agalsidase beta
Fabry disease
(Fabrazyme)
Inhibitors of synthesis of toxic molecules
Chenodeoxycholic
Cerebrotendinous xanthomatosis
acid
Miglustat
Gaucher disease
Heme arginate
Neuroprotective
Dextrometorphan
Ketamine
1
250 mg/kg/day
intravenous
Oral or
intravenous
Not reported
10 mg/kg/day
50 mg/kg/day
Oral
Oral
Not reported
Not reported
Usually 60 U/kg per 2 weeks
0.2 mg/kg per 2 weeks
Intravenous
Intravenous
Not reported
Not reported
1 mg/kg per 2 weeks
Intravenous
Not reported
750 mg/day in three divided doses
Oral
Not reported
300 mg/day in three divided doses
Oral
Porphyrias
3 mg/kg/day for 4 days
Intravenous
Diarrhea, weight
loss, tremor
Not reported
Nonketotic hyperglycinemia
Nonketotic hyperglycinemia
5 mg/kg/day
1–30 mg/kg/day in four divided doses
Oral
Oral
Not reported
Not reported
Adapted from Walter JH and Wraith JE (2006) Treatment: present status and new trends. In Inborn Metabolic Diseases: Diagnosis and Treatment,
81–100 (Eds Saudubray JM et al.) Berlin: Springer-Verlag. Abbreviations: ASS, argininosuccinate synthetase; CBlC, cobalamin C; CPS, carbamoyl
phosphate synthase; MTHFR=methylene tetrahydrofolate reductase; NA, not applicable; OTC=ornithine transcarbamylase; PTP, pyruvoyl
tetrahydrobiopterin synthase.