Table 1.

Summary of mutations/sequence variants found in PNPO that have an effect on PNPO enzyme activity

Group	Patient	Current age	Mutation/sequence variant	Presumed effect	Age of seizure onset	References
(i)	1	4 y	c.[284G>A] (M) + c.[148G> A];c.[364-1G>A]a (P)	p.R95H (M) + p.E50K;Splice errors a (P)	30 min	Mills et al., 2005; Khayat et al., 2008
	2	5 y 2 m	c.[98A>T] + c.[98A>T]	p.D33V + p.D33V	6 h	Hoffmann et al., 2007
	3	2 y 7 m	c.[637C>T] + c.[637C>T]	p.P213S + p.P213S	90 min	Novel
	4*	4 m	c.[637C>T] + c.[637C>T]	p.P213S + p.P213S	None*	Novel
	5	1 y	c.[283C>T] (M) + c.[283C>T] (P)	p.R95C (M) + p.R95C (P)	2 h	Khayat et al., 2008
	6	4 y	c.[641dupA] +?**	p.Q214fs +? **	5 h	Novel
(ii)	7	6 y 5 m	c.[347G>A] (M) + c.[347G>A] (P)	p.R116Q (M) + p.R116Q (P)	5 m	Novel
(iii)	8	9 y	c.[347G>A] + c.[347G>A]	p.R116Q + p.R116Q	3 h	Novel
	9	2 y	c.[98A>T] + c.[998A>T]	p.D33V + p.D33V	3 w	Hoffmann et al., 2007
	10	23 y	c.[98A>T] + c.[358G>A]	p.D33V + p.E120K	2 m	Hoffmann et al., 2007 + novel
	11	21 y	c.[98A>T] (P) + c.264-21_ 264-1delinsC (M)	p.D33V (P) + Splice errors (M)	3 h	Hoffmann et al., 2007 + novel
	12	41 y	c.[98A>T] + c.[347G>A] + c. [673C>T]	p.D33V + p.R116Q + p.R225Cb	14 d	Hoffmann et al., 2007 + novel + Veerapandiyan et al., 2011
	13	9 y	c.[674G>A] + c.[674G>A]	p.R225H + p.R225H	24 h	Novel
	14	3 y	c.[347G>A];c.[674G>A] + c.[347G >A];c.[674G>A]	p.R116Q;p.R225H + p.R116Q;p.R225H c	30 min	Novel
	15	9 y	c.[347G>A];c.[674G>A] + c.[347G >A];c.[674G>A]	p.R116Q;p.R225H + p.R116Q;p.R225H c	10 h	Novel

(i) Neonatal onset seizures responding to pyridoxal 5’-phosphate;

(ii) Infantile spasms (onset 5 months) responsive to pyridoxal 5’-phosphate;

(iii) Seizures starting under 3 months of age responding to pyridoxine.

Where parent DNA available inheritance was investigated and the allele carrying the mutation is indicated as P (paternal) or M (maternal).

*Sibling of Patient 3, no seizures as treated prophylactically;

**Second mutation not found, complementary DNA and genomic DNA sequenced;

^ac.[148G>A] and c.[364-1G>A] were inherited in cis, this was confirmed by analysing parental DNA;

^b No parental DNA was available to ascertain which muation R116Q was in cis with;

^cAssume that R116Q has been inherited in cis with R225H, no parental DNA was available to confirm this.