Gastrointestinal side effects in children with Wilson's disease treated with zinc sulphate

Table 1 ATP7B mutations in patients with Wilson’s disease treated with zinc sulphate

Mutation analysis	n
p.H1069Q/p.H1069Q	22
Diagnosis not confirmed by mutation analysis	1
p.H1069Q/-	7
p.H1069Q/p.Q1351X	2
p.H1069Q/p.A1135fs	2
p.V845fs/-	2
p.H1069Q/p.E507fs	1
p.H1069Q/p.C985Y	1
p.H1069Q/p.L1325fs	1
p.H1969Q/p.W779X	1
p.H1069Q/p.R969Q	1
p.H1069Q/p.T737I	1
p.H1069Q/p.P1273L	1
p.H1069Q/p.V772_I774del	1
p.H1069Q/p.Arg969Gln	1
p.H1069Q/p.G1341R	1
p.A1135fs/p.A1135fs	1
p.A1135fs/p.R1319X	1
p.G1158fs/p.G1158fs	1
p.W779X/p.W779R	1
p.Q1351X/-	1
p.A1135fs/-	1
p.N1270S/-	1

Table 2 Characteristic of patients with side effects during zinc therapy

No.	Sex	Age of onset of symptoms (yr)	Age of diagnosis (yr)	Mutation analysis		Zinc sulphate therapy-dosagescheme (mg)	Treatment history	Cause of conversion to D-penicillamine	Cause of conversion to zinc acetate	Cause of additional intervention	Endoscopic examination
1	M	7	8	p.V845fs	-	2 × 45	ZS - P - ZA	Abdominal pain	Rash		No
2	F	Asymptomatic, positive family history	15	p.V845fs	-	3 × 45	ZS - P - ZA	Abdominal pain	Abdominal pain		No
3	M	Asymptomatic, positive family history	6	p.Q1351X	-	3 × 45	ZS - P	Abdominal pain			No
4	M	7	16	p.W779X	p.W779R	3 × 45	ZS - P	Abdominal pain, loss of appetite			No
5	F	7	9	p.H1069Q	p.H1069Q	3 × 45	ZS - P	Vomiting			No
6	M	Lack of data	12	p.H1069Q	p.P1273L	3 × 45	ZS + PPI			Abdominal pain, symptoms of GERD	No
7	M	11	12	-	-	3 × 45	ZS - ADS			Abdominal pain	No
8	F	11	11	p.N1270S	-	3 × 45	ZS - P	Nausea			No
9	M	12	13.5	p.G1158fs	p.G1158fs	5 × 45	ZS - P	Nausea, vomiting			No
10	F	13	14	p.H1069Q	p.Q1351X	3 × 45	ZS - ZA		Nausea		No
11	F	Lack of data	12	p.H1069Q	p.T737I	3 × 45	ZS - P	Nausea			No
12	M	8	13	p.H1069Q	p.V772_I774del	3 × 45	P - ZS - ADS			Nausea	No
13	F	7	7	p.H1069Q	p.G1341R	2 × 45	ZS - P	Abdominal pain			No
14	M	7	7	p.A1135fs	-	2 × 45	ZS - ZA - P	Elevated transaminases	Abdominal pain		No
15	F	Asymptomatic, positive family history	5	p.H1069Q	p.H1069Q	2 × 45	ZS + PPI - P	Abdominal pain			Yes
16	F	8	8	p.H1069Q	p.H1069Q	2 × 45	ZS +PPI - P	Abdominal pain			Yes
17	F	14	14	-	-	3 × 45	ZS + PPI			Abdominal pain	Yes
18	F	12	12	-	-	3 × 45	ZS +PPI - P	Abdominal pain			Yes
19	M	Asymptomatic, positive family history	Lack of data	-	-	2 × 45	ZS +PPI - P	Abdominal pain			Yes
20	F	10	10	p.H1069Q	-	3 × 45	ZS + PPI			Abdominal pain	Yes
21	F	9	9	-	-	1 × 45	ZS + PPI			Abdominal pain	Yes

ZS: Zinc sulphate therapy; P: D-penicillamine therapy; ZA: Zinc acetate therapy; PPI: Proton pump inhibitor therapy; ADS: Alternative dosage scheme; GERD: Gastroesophageal reflux disease; M: male; F: Female.

Table 3 Characteristic of patients with persistent abdominal pain

No.	Abdominal pain before zinc sulphate therapy	Duration of zinc sulphate therapy before abdominal pain occurred (wk)	EGD before intervention	Intervention	Abdominal pain after intervention	EDG after intervention	Additional intervention	Abdominal pain after additional intervention	EGD after additional intervention
1	Yes	Lack of data	Gastritis with mucosal ulceration	PPI	Yes	Ulcer scar	No	-	-
2	No	96	Gastritis with mucosal ulceration	PPI	No	No	No	-	-
3	No	28	Gastritis with mucosal ulceration	PPI	Yes	Gastritis with mucosal ulceration	Conversion to D-penicillamine	No	No
4	No	144	Gastritis with mucosal ulceration	PPI	Yes	Gastritis	Conversion to D-penicillamine	No	No
5	No	12	Gastritis with mucosal erosion	PPI	No	No	No	-	-
6	No	96	Gastritis with mucosal ulceration	PPI	Yes	No	Conversion to D-penicillamine	No	Normal findings
7	No	96	Gastritis with mucosal erosion	PPI	Yes	No	Conversion to D-penicillamine	No	Normal findings

EGD: Esophagogastroduodenoscopy; PPI: Proton pump inhibitor.

Table 4 Characteristic of mutation analysis in two groups of patients with Wilson’s disease: with and without side effects during zinc sulphate therapy

Mutation analysis	No. of patients during zinc sulphate therapy
	Without side effects	With side effects
Homozygous for p.H1069Q mutation	16	3
Compound heterozygous for p.H1069Q mutation	8	5
Carrier for p.H1069Q mutation	4	1
Carrier for a mutation other than p.H1069Q	0	5
Mutation other than p.H1069Q on two alleles	2	2
Lack of data	2	5