Table 5.
Therapeutic modalities for IEMs causing PIND.
| IEM name | Therapeutic modality (-ies) | Level of evidence | Treatment effect | References |
|---|---|---|---|---|
| α-mannosidosis | HSCT | 4/5 | Stabilizes clinical deterioration | Treatable ID |
| Aspartylglucosaminuria | HSCT | 4/5 | Stabilizes clinical deterioration | Treatable ID |
| Arginase 1 deficiency | Dietary protein restriction, arginine supplement, sodium benzoate, phenylbutyrate | 2b | Prevents metabolic decompensation; stabilizes clinical deterioration; improves behavior, seizure control, neurological and systemic manifestations | Treatable ID |
| Biotinidase deficiency | Biotin supplements | 2c | Improves psychomotor development/IQ, neurological and systemic manifestations | Treatable ID |
| CAD deficiency | Uridine supplements | 4 | Seizure control, stabilizes clinical deterioration, improves psychomotor development/IQ | Koch et al. (31) |
| Carbamoylphosphate synthetase I deficiency* | Dietary protein restriction, arginine supplement, sodium benzoate, phenylbutyrate | 2b | Prevents metabolic decompensation; stabilizes clinical deterioration; improves behavior, seizure control, neurological and systemic manifestations | Treatable ID |
| Cerebral folate receptor-α deficiency | Folinic Acid | 4 | Stabilizes clinical deterioration; improves psychomotor development/IQ; seizure control and neurological manifestations | Treatable ID |
| Cerebrotendinous xanthomatosis | Chenodeoxycholic Acid, HMG Reductase Inhibitor | 4 | Stabilizes clinical deterioration, improves behavior, neurological and systemic manifestations | Treatable ID |
| COQ2 deficiency | CoQ supplements | 4 | Improves neurological manfestation and seizure control | Treatable ID |
| Gaucher disease (type III) | HSCT | 4/5 | Stabilizes clinical deterioration, improves systemic manifestations | Treatable ID |
| Glucose transporter deficiency | Ketogenic or analog diets | 2b | Improves seizure control, improves neurological manifestations, improves psychomotor development/IQ | Daci et al. (32) |
| Guanidinoacetate methyltransferase (GAMT) deficiency | Arginine restriction, Creatine and Ornithine supplements | 4 | Stabilizes clinical deterioration; improves behavior, seizure control and neurological manifestations | Treatable ID |
| HSD10 deficiency | Avoid fasting, Sick day management, Isoleucine restricted diet | 5 | Prevents metabolic decompensation | Treatable ID |
| Hyperornithinemia-hyperammonemiahomocitrullinemia syndrome | Dietary protein restriction, Ornithine supplement, sodium benzoate, phenylacetate | 4 | Prevents metabolic decompensation; stabilizes clinical deterioration; improves behavior, seizure control, neurological and systemic manifestations | Treatable ID |
| Krabbe disease | HSCT | 2a | Stabilizes clinical deterioration | Escolar et al. (33) |
| l.o. Glutaric aciduria type 1 | Lysine Restriction, Carnitine supplements | 2c | Prevents metabolic decompensation; stabilizes clinical deterioration; improves neurological and systemic manifestations | Treatable ID |
| l.o. Metachromatic leucodystrophy | HSCT | 4/5 | Stabilizes clinical deterioration | Treatable ID |
| Maple syrup urine disease (variant) | Amino acids, Avoid fasting | 4 | Stabilizes clinical deterioration; prevents metabolic decompensation; improves behavior | Treatable ID |
| Menkes disease occipital horn syndrome | Copper Histidine | 4 | Stabilizes clinical deterioration | Treatable ID |
| Methylcobalamin deficiency, cblE type | Hydroxy-/Methylcobalamin, Betaine | 4 | Prevents metabolic decompensation, stabilizes clinical deterioration; improves systemic manifestations | Treatable ID |
| Methylenetetrahydrofolate reductase deficiency | Betaine supplements, +/– Folate, Carnitine, Methionine supplements | 4 | Prevents metabolic decompensation; stabilizes clinical deterioration; improves systemic manifestations | Treatable ID |
| Methylglutaconic aciduria type I | Carnitine supplements, Avoid fasting, Sick day management | 5 | Prevents metabolic decompensation | Treatable ID |
| Methylmalonic aciduria and homocystinuria, cblC type | Hydroxocobalamin | 4 | Prevents metabolic decompensation; stabilizes clinical deterioration; improves systemic manifestations | Treatable ID |
| Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-like episodes (MELAS) | Arginine supplements | 4/5 | Prevents metabolic decompensation, stabilizes clinical deterioration, improves seizure control & neurological manifestations | Treatable ID |
| Molybdenum cofactor deficiency | Cyclic pyranopterin monophosphate (cPMP) supplements | 2b | Stabilizes clinical deterioration; improves neurological manifestations | Schwahn et al. (34) |
| Mucopolysaccharidosis type 1 (MPS I) |
HSCT | 1c | Stabilizes clinical deterioration; improves systemic manifestations | Treatable ID |
| Mucopolysaccharidosis type 2 (MPS II) |
HSCT | 4/5 | Stabilizes clinical deterioration; improves systemic manifestations | Treatable ID |
| Mucopolysaccharidosis type 3A (MPS IIIA) |
HSCT | 4/5 | Stabilizes clinical deterioration | Treatable ID |
| Mucopolysaccharidosis type 3B (MPS IIIB) |
HSCT | 4/5 | Stabilizes clinical deterioration | Treatable ID |
| Mucopolysaccharidosis type 3C (MPS IIIC) |
HSCT | 4/5 | Stabilizes clinical deterioration | Treatable ID |
| Mucopolysaccharidosis type 3D (MPS IIID) |
HSCT | 4/5 | Stabilizes clinical deterioration | Treatable ID |
| Mucopolysaccharidosis type 7 (MPS VII) |
HSCT | 4/5 | Stabilizes clinical deterioration | Treatable ID |
| Neuronal ceroid lipofuscinosis type 2 | Enzyme replacement therapy | 1c | Stabilizes clinical deterioration | Geraets et al. (35) |
| Niemann-Pick disease type C1 | Miglustat | 1b | Stabilizes clinical deterioration; improves neurological manifestations | Treatable ID |
| Niemann-Pick disease type C2 | Miglustat | 1b | Stabilizes clinical deterioration; improves neurological manifestations | Treatable ID |
Legend: l.o., Late onset.
HSCT, Haematologic stem cell transplantation.
Levels of evidence (source www.cebm.net): 1a. Systematic review of randomized controlled trials (RCTs), 1b. Individual RCT, 1c. All or none. 2a. Systematic review of cohort studies, 2b. Individual cohort study, 2c. “Outcomes” research, 3. Systematic review of case-control studies, 4.Individual case-control study or case-series/report, 4/5. Single case report, 5. Expert opinion without critical appraisal.