Table 1.

Clinical characteristics of all patients described in this study who carry the NDUFS6 c.309+5G>A variant in homozygosity

Clinical features	Family 1		Family 2	Family 3
	II-1	II-2	II-1	II-1	II-2
Origin	Spanish		Turkish	Greek
Consanguinity	No		Yes	No
Clinical diagnosis	Axonal CMT		Axonal CMT	Axonal CMT	Axonal CMT
Age at onset (y)	1.25	1.25	10	10	10
Age at last examination (y)	52	44	19	19	17
Initial symptoms	Late walking		Distal muscle weakness	Unsteady gait, ataxia	Unsteady gait, frequent falls
Main symptoms	Severe distal LL weakness and atrophy, foot deformities		Distal muscle weakness	Severe LL weakness, ataxia	Distal LL weakness
Disease course	Minimal progression	Minimal progression	Minimal progression	Minimal progression	Minimal progression
Gait	Steppage	Steppage	Steppage	Steppage, need bilateral assistance, ankle foot orthoses	Steppage
Muscle weakness (MRC)
UL proximal	5	5	5	5	5
UL distal	5	0-3	4	4	5-
LL proximal	5	5	5	4	5
LL distal	0	0	Dorsiflexion: 0, plantar flexion: 2	0	Dorsiflexion: 0, plantar flexion: 3
Muscle wasting	Severe dLL, minimal dUL	Severe dLL, dUL	dLL	dLL, minimal dUL	dLL
Tendon reflexes	Achilles: 0, other: 3	Achilles: 0, other: 1	Achilles: 0, knee: 1, other: 2	Achilles: 0, knee: 1, UL: 3	Achilles: 0, other: 2
Skeletal deformities	Pes cavus		Pes cavus	Pes cavus	Pes cavus
Sensory loss
Light touch	LL	LL	dLL	LL	No
Pain/temperature	LL	LL	dLL	LL	dLL
Proprioception	No	No	No	LL	No
Vibration	LL, dUL	LL, dUL	No	LL, dUL	dLL
Nystagmus	Yes	Yes	Yes	Yes	Yes
Involuntary movements	None	None	None	Tremor, chorea, athetosis	Chorea, myoclonus, left UL dystonia
Brain MRI	Normal	Normal	Normal	“Eye-of-the-tiger” sign in basal ganglia	Unknown
Biochemical assays
Serum lactateh	2.5 mmol/La	1.9 mmol/Lb	1.03 mmol/Lc	2.02 mmol/Ld	NA
Serum pyruvatei	84 μmol/Le	85 μmol/Lf	NA	120 μmol/Lg	NA
Lactate/pyruvatej	29.8	22.4	NA	16.83	NA
Additional features	NA	NA	Intellectual disability	NA	Rolandic epilepsy

Abnormal values are highlighted in bold. Muscle weakness scale (MRC): 0 = no contraction, 1 = flicker or trace of contraction, 2 = active movement, with gravity eliminated, 3 = active movement against gravity, 4 = active movement against gravity and resistance, 5 = normal power. Tendon reflexes scale: 0 = absent, 1 = reduced, 2 = normal, 3 = increased, 4 = clonus.

CMT, Charcot-Marie-Tooth disease; dLL, distal lower limb; dUL, distal upper limb; LL, lower limb; UL, upper limb.

^a22.52 mg/dL.

^b17.12 mg/dL.

^c9.28 mg/dL.

^d18.20 mg/dL.

^e0.74 mg/dL.

^f0.75 mg/dL.

^g1.06 mg/dL.

^hReference range 0.5-2.2 mmol/L (4.5-19.82 mg/dL).

ⁱReference range 40-130 μmol/L (0.35-1.14 mg/dL).

^jReference value <25.