Table 1.

Summary of all reported NAXE variants and associated cases of PEBEL1. Molecularly confirmed probands and their siblings (confirmed or unconfirmed), grouped under the pathogenic NAXE variants, are shown. Reported clinical findings, treatments, and outcomes are shown. Bolded are patients that were alive at assessment 1 year or more after diagnosis.

Case	Genetics of NAXE transcript: NM_144772.2, protein: NP_658985.2				SexA	Age	Outcome	Neurologic phenotype
	Variant 1	Δ product	Variant 2	Δ product				Hypotonia	Loss of motor milestones	Ataxia	Movement d/o	Bulbar	Seizures
1	c.281C>A	p.Ala94Asp	c.281C>A	p.Ala94Asp	♀	6–12	Death at 1-3y	+	+
2					♀	m		+	+
3					♀			+	+
4					♂			+	+
5					♂		Death at 10 yC	+	+
6	c.177C>AD	p.Tyr59*	c.177C>AD	p.Tyr59*	♂	20 m	Death at 21 m	+		+	Quadriparesis, torticollis
7					♀	19 m	Death at 24 m	+		+	Quadriparesis
8	c.196C>TD	p.Gln66	c.516 + 1G>AD		♀	15 m	Death at 24 m	+			Tremor
9	c.804_807 delinsAD	p.Lys270del	c.804_807 delinsAD	p.Lys270del	♂	16 m	Death at 18 m			+
10	c.804_807 delinsAD	p.Lys270del	c.368A>T	p.Asp123Val	1 ♂	2 y	Alive at 3 y with residual ataxia E	+	+	+	Torticollis
11	c.653A>T	p.Asp218Val	c.743delC	p.Ala248Glufs*26	♂	16 m	Death at 29 m	+		+		Dysarthria	+
12					?	8 m	Death at 24 m
13	c.653A>T	p.Asp218Val	c.743_744delCA	p.Ala248Thrfs	♂F	8 m	Death at 24 m		+				+
14					♂F	?	?		+				+
15	c.757G>AD	p.Gly253Ser	c.665-1G>AD		♂	3 y	Death at 6 y			+	Recurrent falls	Dysarthria, dysphagia
16	c.757G>AD	p.Gly253Ser	c.665-1G>AD,G		♀	20 y	Death at 22 y			+	Myoclonus
17	c.757G>AD	p.Gly253Ser	c.665-1G>AD		♀	22 y	Alive at 29 y, nonambulatory E				Myoclonus, perioral dyskinesia, spasticity	Dysarthria	+
18	c.733A>C	p.Lys245Gln	c.733A>C	p.Lys245Gln	♀	20 m	Alive at 5.5 y with unsteady gateH1,I	+	+	+	Quadriparesis, tremor	Dysarthria	+
19	c.733A>C	p.Lys245Gln	c.733A>C	p.Lys245Gln	♀F	4 y	Death at 4 y	+	+
20	c.652G>A	p.Asp218Asn	c.652G>A	p.Asp218Asn	♂	3 d	Death at 4–6 m	+	+
21					?	?		+	+
22					?	?		+	+
23	c.640A>G	p.Ile214Val	c.640A>G	p.Ile214Val	♂	7y	Not reported
24					♀	?	diseased, age not reported
25	c.386G>C	p.Arg129Pro	c.641 T>G	p.Ile214Ser	♂	2 y	Death at 3 y	+	+	+	Quadriparesis, torticollis	Dysarthria	+
26	c.255A>T	p.Glu85Asp	c.361G>A	p.Gly121Arg	♂	2 y	Death at 3 y	+		+
27	c.255A>T	p.Glu85Asp	c.361G>A	p.Gly121Arg	♂	2y	Alive at 4 y with mild myopathy H2	Mild		+
28	c.565G>A	p.Gly189Ser	c.565G>A	p.Gly189Ser	♂	1 y	Death by 3 y	+	+	+	UE hyperkinesia
29					♂	1 y	Death by 20 m	+	+				+
30	c.368A>T	p.Asp123Val	c.733A>C	p.Lys245Gln	♀F	2.5 y	Alive at 21 y, ventilatordependent and bedridden		+

Abbreviations: ND = not determined; m = month(s); y = year(s); Nl = normal; R = regression; T2HI = T2 hyperintensities; DR = diffusion restriction on diffusion weighted imaging; Abn = Abnormal; PR = pigmentary retinopathy; GDD = global developmental delays; HTN = hypertension; skin = Pellagra-like erythematous desquamating rash involving the neck face and torso also described as Lyell-like (toxic epidermal necrolysis) in some reports; WM = white matter; FTT = failure to thrive; UE = upper extremities; FSGS = focal segmental glomerulosclerosis; CK = creatine kinase.

^ANumber includes family members presenting with a similar phenotype even in the absence of molecular confirmation.

^BIncreased lactate in cerebrospinal fluid (CSF) or an abnormal lactate peak on MR spectroscopy.

^CPatient was bedridden and ventilator-dependent since diagnosis.

^DNo protein expression in fibroblasts.

^ETreated with niacin (80–200 mg/day).

^FInformation obtained from a retrospective whole exome sequencing study; phenotypic characterization is limited to the human phenotype ontology's (HPO) standardized annotation.

^GSuspected to be triggered by alcohol and tetrahydrocannabinol consumption.

^H1Treated with nicotinamide, 30 mg/day; along with thiamine 60 mg/day, riboflavin 3 mg/day, pyridoxine 3 mg/day, and coenzyme Q10.

^H2Treated with nicotinamide; and coenzyme Q10, thiamine and riboflavin (doses not reported).

^ISuffered two crises, recovered from the first one after 2 months of rehabilitation with residual ataxia and hypotonia.

^JThe patient is a product of consanguineous union. Brain malformations in this case, not seen in others, may be related to other genetic variations.