Acute liver failure with hemolytic anemia in children with Wilson’s disease: Genotype-phenotype correlations?

Table 1 Clinical and laboratory characteristics in Wilson’s disease children with acute liver failure and hemolytic anemia

Parameter		All (n = 51)	ALF and hemolytic anemia(8 pts)	Other clinical forms(43 pts)	P value
Females, n (%)		26 (50.98)	8 (100)	18 (41.86)	0.00252
Mean age (yr)		12.36 ± 3.74	14.59 ± 2.21	11.59 ± 3.79	0.03598
ALT (IU/L)		131.54 ± 119.69	87.38 ±154.07	142.24 ± 110. 04	0.24969
AST (IU/L)		125.05 ± 88.73	78.62 ± 47.44	136.30 ± 93.16	0.09950
TB (mg/dL)		5.41 ± 12.93	22.55 ± 21.95	0.99 ± 0.95	0.000002
DB (mg/dL)		4.20 ± 11.56	18.84 ± 20.40	0.42 ± 0.51	0.000007
GGT (IU/L)		83.54 ± 43.44	97.71 ± 57.14	80.44 ± 40.33	0.34731
WBC (mm3)		8568 ± 7360	14838 ± 14185	6666 ± 1799	0.00415
Hb (g/dL)		12.15 ±2.96	7.4 ± 2.39	13.51 ± 1.22	0.000000
PLT (mm3)		253306 ±125421	164875 ± 74043	278571 ± 126455	0.02142
INR		2.94 ± 6.37	7.53 ± 11.34	1.18 ± 0.27	0.01359
KF ring, n (%)		9 (17.65)	3 (37.50)	6 (13.95)	0.10868
Ceruloplasmin (mg/dL)		9.81 ± 6.118	7.98 ± 5.77	10.11 ± 6.19	0.39976
Urinary copper (μg/24 h)		648.94 ± 1093.90	2 236.33 ± 2 174.46	384.38 ± 455.04	0.000006
Outcome, n (%)					0.00121
	Survivors	47 (92.16)	5 (62.50)	42 (97.67)
	Transplanted	2 (3.92)	2 (25.00)	0
	Deceased	2 (3.92)	1 (12.50)	1 (2.33)

ALF: Acute liver failure; ALT: Alanine-aminotransferase; AST: Aspartate-aminotransferase; TB: Total bilirubin; DB: Direct bilirubin; GGT: Gamma-glutamyl transferase; WBC: White blood cells; Hb: Hemoglobin; PLT: Platelets; INR: International normalized ratio; KF ring: Kayser-Fleisher ring.

Table 2 Variants of ATP7B gene in children with hemolytic anemia and acute liver failure

Variants		Hemolytic Anemia + ALF (8 patients)	Other clinical forms (44 patients)	P value
p.Trp939Cys (c.2817G>T)	5 homozygotes	6 (42.86%)	4 (4.55%)	0.0000
p.Lys844Ter (c.2530A>T)	1 homozygotes	4 (28.57%)	1 (1.14%)	0.0000
	3 heterozygotes
p.Gly1341Asp (c.4021G>A)	10 homozygotes	4 (28.57%)	23 (26.14%)	0.8482
	7 heterozygotes
p.His1069Gln (c.3207A>G)	12 homozygotes	0	39 (44.32%)	0.0015
	15 heterozygotes
Other variants	1 homozygotes	2 (14.29%)	19 (21.59%)	0.5304
	19 heterozygotes
Total alleles		14 (100%)	88 (100%)

ALF: Acute liver failure.

Table 3 Data regarding the patients evaluated for the HSD17B13:TA variant

	All	HSD17B13 genotype
		T/T	TA/T	TA/TA
n (%)	33	19 (57.58)	12 (36.36)	2 (6.06)
Females, n (%)	16	11	5	0
Mean age (yr)	11.67 ± 3.12	11.09 ± 3.45	12.14 ± 2.25	14.70 ± 3.24
Clinical presentation, n (%)
ALF and/or hemolytic anemia	7 (21.21)	5 (71.43)	2 (28.57)	0
Less severe hepatic forms	26 (78.79)	14 (53.85)	10 (38.46)	2 (7.69)
ATP7B variant
p.His1069Gln (c.3206A>G)/p.His1069Gln (c.3206A>G)	5	2	3	0
p.His1069Gln (c.3206A>G)/p.Gly1341Asp (c.4021G>A)	6	3	3	0
p.His1069Gln (c.3206A>G)/other	7	4	3	0
p.Gly1341Asp (c.4021G>A)/p.Gly1341Asp (c.4021G>A)	7	3	2	2
p.Trp939Cys (c.2817G>T)/p.Trp939Cys (c.2817G>T)	4	4	0	0
p.Trp939Cys (c.2817G>T)/other	1	1	0	0
p.Lys844Ter (c.2530A>T)/p.Lys844Ter (c.2530A>T)	1	1	0	0
p.Lys844Ter (c.2530A>T)/ other	2	1	1	0

ALF: Acute liver failure.