Table 1.

Demography, genotype and clinical characteristics of the 28 studied patients with WRS

Patient	Country of origin	Gender	Age at diagnosis and presenting features	EIF2AK3 mutation	Acute hepatitis – age at 1st episode and frequency	Acute hepatic failure –age at onset, number, and outcomes	Other features	Prognosis/comments
1.1	KSA	Male	Hyperglycaemia at 8 weeks	p.W430X (c.1290G>A)	1 episode at 8 months	No	No	Alive at 18 months old
2.1 [17]	KSA	Male	DKA at 21 weeks	p.V349Sfs*3 (c.l044_1057del)	20 months; 8 episodes (first after reporting)	1 fatal episode at 6 years	SD, SS, FTT and impaired RF during hepatitis	Died at 6 years
3.1 [4, 17]	KSA	Female	DKA and hepatitis at 8 weeks	p.V349Sfs*3 (c.l044_1057del)	8 weeks; 20 episodes	2 episodes at 3 years and 1 fatal at 7.5 years	No	Died at 7.5 years (after initial reporting)
3.2 [17]	KSA	Female	DKA and hepatitis at 10 weeks	p.V349Sfs*3 (c.l044_1057del)	10 weeks; 8 episodes	1 fatal episode at 2 years	SD, SS and impaired RF during hepatitis	Died at 2 years
3.3 [17]	KSA	Male	Hyperglycaemia at 6 weeks	p.V349Sfs*3 (c.l044_1057del)	2 years; once proceeded to acute hepatic failure	1 fatal episode at 2 years	No	Died at 2 years
4.1 [17]	KSA	Male	DKA at 8 weeks	p.V349Sfs*3 (c.l044_1057del)	18 months; 4 episodes (first after reporting)	1 episode (after first reporting)	No	Alive at 6 years
5.1a	KSA	Male	Hyperglycaemia at 2 years	P.W163X (c.491G>A)	2.4 years; once proceeded to acute hepatic failure	1 treated conservatively	Impaired RF during hepatitis episode	Alive at 5 years
6.1a	KSA	Male	Hyperglycaemia at 1.5 years	p.N420Tfs*14 (c.l259del)	2.5 years; once proceeded to hepatic failure	1 fatal episode at 7 years	SD, SS and impaired RF during hepatitis	Died at 7 years
7.1	Jordan	Male	DKA and hepatitis at 6 weeks	p.G1010D (c.3029G>A)	6 weeks; 4 episodes	1 fatal episode at 3.5 years	SD, SS, PH, ASD, DD and epilepsy	Died at 3.5 years
8.1a	Kuwait	Male	Hyperglycaemia at 15 days	FS 523STOP (delGAAA1639-42)	10 months; once proceeded to acute hepatic failure	1 fatal episode at 10.5 months	Impaired RF during hepatitis episode	Died at 10.5 months
9.1	Iraq	Male	Hyperglycaemia at 7 weeks	p.W520X (c.1560G>A)	No	No	No	Alive at 14 months; siblings died of WRS
10.1	Lebanon	Female	DKA at 11 weeks	p.R1064X (c.3190C>T)	11 months; 1 episode recovered spontaneously	No	Impaired RF during hepatitis and deafness	Alive at 15 months; siblings died of WRS
11.1	Oman	Male	Hyperglycaemia at 4 weeks	P.Y588X (c.1764T>G)	10 months; 6 episodes	2 episodes, 1 led to death	Neutropenia, SD, SS, FTT, DD and ADHD	Died at 6.5 years; had liver biopsy for persistent hepatomegaly
11.2	Oman	Female	DKA and hepatitis at 6 weeks	P.Y588X (c.1764T>G)	6 weeks; 5 episodes	1 treated conservatively	Neutropenia and FTT	Alive at 5 years
12.1	UAE	Female	DKA at 6 weeks	p.W430X (c.!290G>A)	8 weeks; 9 episodes	1 treated conservatively	Anaemia and RH	Alive at 10 months; had liver biopsy
12.2	UAE	Female	DKA at 10 weeks	p.W430X (c.1290G>A)	11 weeks; 7 episodes	4 episodes treated conservatively	SD, SS anaemia, neutropenia, squint and RH	Alive at 2.5 years; had liver biopsy
12.3 [4]	UAE	Male	DKA and hepatitis at 7 weeks	p.W430X (c.1290G>A)	7 weeks; 7 further episodes	1 fatal episode	SD, SS, anaemia, neutropenia and RH	Died at 7 years
12.4 [4]	UAE	Male	DKA and hepatitis at 6 weeks	p.W430X (c.1290G>A)	6 weeks; >8 episodes	3 episodes, 1 resulted in death	SD, SS, anaemia, neutropenia and RH	Died at 4 years
12.5 [4]	UAE	Male	DKA at 6 weeks	p.W430X (c.1290G>A)	8 weeks; once/3 months	6 episodes, 1 resulted in death	SD, SS, anaemia, neutropenia and RH	Died at 5 years
12.6	UAE	Female	Hyperglycaemia and hepatitis at 7 weeks	p.W430X (c.1290G>A)	7 weeks; 6 episodes	4 episodes treated conservatively	Pancytopenia, FTT and RH	Alive at 2.4 years; had liver biopsy
13.1 [4]	UAE	Male	Hyperglycaemia at 14 months	P.I650T (c.1949T>C)	1 episode at 2 years; none since transplant	1 episode led to transplant	Anaemia, SD and SS	Alive at 8 years
14.1 [4]	UAE	Male	DKA at 8 weeks	P.G956E (c.2867G>A)	10 weeks; >15 episodes	1 fatal episode (after reporting)	SD, SS and anaemia	Died at 15 years (after initial reporting)
15.1	UAE	Male	Hyperglycaemia at 8 weeks	P.E524X (c.l567_1570del)	9 months; 3 episodes	1 episode treated conservatively	SD and anaemia	Alive at 18 months
16.1	UAE	Female	DKA at 6 weeks	p.? (c.1427-?_2490+?del)	8 months; 2 episodes	1 fatal episode	No	Died at 2.9 years
17.1	Kuwait	Male	Hyperglycaemia at 2 months	P.S991N (c.2972G>A)	14 months; 2 episodes	2 episodes treated conservatively	DD, SD, SS and PH	Alive at 17.5 years
18.1	Sudan	Male	Hyperglycaemia, at 2 months	p.P269fs (c.802_803dup)	No	No	DD and SD	Alive at 3.5 years
19.1	Sudan	Female	Hyperglycaemia at 2 months	P.Y989X (c.2967T>A)	No	No	No	Alive at 3 years; twin brother healthy
20.1	Sudan	Male	Hyperglycaemia at 2 months	p.? (c.1647+2T>A)	No	No	FTT	Alive at 2 years

All mutations listed are homozygous. KSA = Kingdom of Saudi Arabia; UAE = United Arab Emirates; DKA = diabetic ketoacidosis; FTT = failure to thrive; SS = short stature; RF = renal function; ADHD = attention deficit hyperactivity disorder; ASD = atrial septal defect; RH = recurrent hypoglycaemia; DD = developmental delay. All nucleotide and amino acid numbering refers to transcript AF110146.1, which contains 7 leucine residues in the microsatellite region of exon one. The c.l427-?_2490+?del and c.1647+2T>A mutations have been listed at the protein level as p.?, which denotes that the protein has not been analyzed, although an effect is expected.

^aThese samples were tested outside Exeter.