Table 2.

Calculation of patients’ severity score¹

Family ID	H		G		B		A		E		D		C
Substitution	p.L138R		p.T142I		p.G249D		p.R257Q		p.P333L		p.E335D		p.R340C
Age at Diagnosis	Age	Score	Age	Score	Age	Score	Age	Score	Age	Score	Age	Score	Age	Score
Optic atrophy	15 yrs	(0.8)	<1 yrs	(1)	8 yrs	(1)	<1 yrs	(1)	<1 yrs	(1)	1.5 yrs	(1)	2 yrs	(1)
Cerebellar atrophy	15 yrs	(0.8)	<1 yrs	(1)	N/A	(0)	N/A	(0)	<1 yrs	(1)	1.5 yrs	(1)	28 yrs	(0.6)
Neuropathy	15 yrs	(0.8)	<1 yrs	(1)	43 yrs	(0.2)	6 yrs	(1)	<1 yrs	(1)	5 yrs	(1)	14 yrs	(0.8)
Wheel chair bound	15 yrs	(0.8)	N/A	(1)	N/A	(0)	N/A	(0)	N/A	(1)	15 yrs)	(0.8)	N/A	(0)
Early lethality	N/A	(0)	1.1 yrs	(1)	N/A	(0)	N/A	(0)	<1 yrs	(1)	N/A	(0)	N/A	(0)
Severity score	3.2		5		1.2		2		5		3.8		2.4
Average protein stability	0.4		0.15		0.85		0.78		0.33		0.38		0.50

¹The presence of each clinical feature counts for 1 point if reported within the first decade of life, while 0.2 points were subtracted for each subsequent decade. For example, our patient developed optic atrophy and neuropathy within the first decade of life [1 optic atrophy + 1 neuropathy = 2.0 points], while the proband possessing the G249D variant developed optic atrophy in the first decade of life [1 point] and neuropathy/spasticity four decades later [1 - (0.2 × 4 decades) = 0.2 point] for a cumulative score [1 optic atrophy + 0.2 neuropathy = 1.2 points]. Early lethality (death before 2 years of age), counted for the maximum 5 points regardless of whether or not the patient presented with all of the above criteria, the rationale being that the lethal cases are always the most severe.