Table 3.
Summary of results in other CMT subtypes and metabolic neuropathies
| Gene, Mutation | Descriptive | First Author, | Phenotype | Study type | Drug | Target effect | Clinical effect | JADAD | OCEBM | ||
| (Ref Seq) (*see | name | Journal | target HPO | (number of | name | (+/– / =) & | (+/– / =) & | score | score | ||
| Supplement 3 | (Year) | term(s) | patients) | description | description | (1– 5) | (1– 5) | ||||
| for other | |||||||||||
| mutations) | |||||||||||
| ELP1, c.2204 + 6T>C, splice site mutation (NM_003640.5) | HSAN3 | Norcliffe-Kaufmann, Neurology (2013) [46] | Nausea &vomiting | RCT (12) | Carbidopa | Not described | + | Decreased nausea &retching | 5 | 2 | |
| ELP1, c.2204 + 6T>C, splice site mutation (NM_003640.5) | HSAN3 | Bar-Aluma, Lung (2018) [47] | Functional respiratory abnormality | RCT (14) | Albuterol sulfate, Ipratropium bromide | Not described | + | Increase in FEV1 &FVC, decrease in airway resistance, decrease in airway obstruction | 5 | 4 | |
| MT-ATP6, m.9185T>C, p.Leu220Pro (NC_012920.1) | CMT2 | Panosyan, Muscle Nerve (2017) [48] | Episodic flaccid weakness | Case series (2) | Acetazolamide | Not described | + | Decreased frequency &severity of episodic weakness | 0 | 4 | |
| PHYH, c.830 C>A, p.Ala277Glu (NM_001037537.1) | Refsum disease | Kohlschutter, J Child Neurol (2012) [30] | Muscle weakness, Distal sensory impairment, Visual impairment | Case study (1) | Phytanic acid-poor diet + extracorporeal lipid apharesis | + | Decrease in blood phytanic acid levels | + | Decrease in neurological &ophthalmological disease progression | 0 | 4 |
| PHYH, c.135-2A>G, splice site mutation (NM_006214.4) | Refsum disease | Finsterer, J Neurol Sci (2008) [29] | Not described (Peripheral neuropathy?) | Case study (1) | Phytanic acid-poor diet (Chelsea diet) | + | Slight decrease in blood phytanic acid levels | + | Decrease in symptoms (subjective) | 0 | 4 |
| SCN9A, c.2428 G>A, p.Val810Met (NM_002977.3) | Painful peripheral neuropathy | Adi, Mol Pain (2018) [49] | Distal sensory impairment, Pain insensitivity | Case study (1) | Carbamazepine | + | Use-dependent channel inhibition | + | Decrease in burning pain | 0 | 4 |
| SLC52A3, c.639 G>C, p.Tyr213Ter + c.374 C>A, p.Thr125Asn (NM_001370085.1) | BVVL | Chaya, Semin Pediatr Neurol (2018) [31] | Muscle weakness | Case study (1) | Riboflavin | + | Increased EGRAC &riboflavin levels | +/= | Slight increase in motor function | 0 | 4 |
| SLC52A2, c.916 G>A, p.Gly306Arg (NM_001253815.2) +*7 other mutations | BVVL | Foley, Brain (2014) [28] | Patient I1: Muscle weakness, Functional respiratory abnormality; Patient E1: Same as I1 + Visual impairment, Hearing impairment | Case series (2) | Riboflavin | + | Decreased (normalised) acylcarnitine levels | + | Patient I1: Increased motor &respiratory function in patient I1; Patient E1: Same as I1 + decreased visual &hearing impairment in patient | 1 | 4 |
| SPTLC1, N/A | HSAN1 | Fridman, Neurology (2019) [50] | Muscle weakness, Distal sensory impairment | RCT (18) | L-serine | + | Significant decrease in deoxysphinganine levels | + | Significant decrease in CMTNS compared with placebo | 5 | 2 |
| SPTLC2, c.547 C>T, p.Arg183Trp (NM_004863.3) | HSAN1C | Auranen, Cold Spring Harb Mol Case Stud (2017) [51] | Muscle weakness, Distal sensory impairment | Case study (1) | L-serine | + | Decreased deoxysphinganine levels | = | Slight increase in CMTNS score | 0 | 4 |
| PMP22, c.215 C>T, p.Ser72Leu (NM_000304.4) | CMT3 | Burns, Pediatr Neurol (2009) [52] | Muscle weakness, Functional respiratory abnormality | Case study (1) | Curcumin | Not described | = | No change in neurophysiology, muscle strength, respiratory function, disability or QoL | 0 | 4 | |
Summary of results in other CMT subtypes and metabolic neuropathies. Key: HSAN3 Hereditary sensory and autonomic neuropathy type 3, CMT2 Charcot-Marie-Tooth type 2, CMT2 Charcot-Marie-Tooth type 3, MTHFR Methylenetetrahydrofolate reductase deficiency, HNPP Hereditary neuropathy with liability to pressure palsies, BVVL Brown-Violetto-Van-Laare syndrome, HSAN1 Hereditary Sensory and Autonomic Neuropathy type 1, HSAN1 C Hereditary Sensory and Autonomic Neuropathy type 1 C, DHA Docosahexaenoic acid, + positive change, - negative change, = no change, NCV nerve conduction velocity, CMAP compound muscle action potential, RCT randomised controlled trial, V50M p.Val50Met mutation, NIS-LL Neuropathy Impairment Score in the Lower Limbs, QoL Quality of Life, FEV1 forced expiratory volume in 1 second, FVC forced vital capacity, eGFR estimated glomerular filtration rate, EGRAC erythrocyte glutathione reductase activity coefficient, mNIS+7 modified Neuropathy Impairment Score (+7 neurophysiologic tests), *Licensed for other indications.