Clinical spectrum and genotype-phenotype correlation of ABCB4 mutations in children: Insights from a North Indian cohort

Table 1 Comparison of clinical, laboratory and genetic parameters between bi-allelic and monoallelic ABCB4 mutations, median (interquartile range)

Parameters	Homozygous/compound HET mutation (n = 16)	HET mutation (n = 10)	P value
General characteristics
Male gender	62.5%	60%	1.00
Median age at symptom onset in months	54 (4, 168)	10.5 (5, 72)	0.40
Median age at presentation in months	60 (4, 172)	18 (11, 126)	0.42
Consanguinity	37.5%	10%	0.19
Positive family history	75%	30%	0.04
Sibling loss	43.8%	33.3%	0.69
Anthropometry
Weight Z-score at admission	-1.09 (-2.03, -0.21)	-1.39 (-2.61, 0.10)	0.97
Height Z-score at admission	-0.91 (-2.72, -0.52)	-2.1 (-3.33, 0.03)	0.57
Weight Z-score at last follow up	-0.42 (-1.29, -0.125)	-0.58 (-1.63, 1.31)	0.90
Height Z-score at last follow up	-0.37(-1.83, 0.33)	-0.76 (-2.23, 0.91)	0.86
Clinical parameters at admission
Jaundice	68.8%	90%	0.35
Pruritus	68.8%	80%	0.66
Ascites	43.2%	0%	0.02
Gastrointestinal bleed	12.5%	0%	0.5
Decompensation at admission	43.8%	0%	0.02
Esophageal varix			0.009
No varix	20%	87.5%
Small varix	40%	12.5%
Large varix	40%	0
Genetics
Missense variants	81.3%	80%	1.00
Recent American College of Medical Genetics class likely pathogenic or pathogenic	100%	30%	< 0.001
Laboratory parameters
First visit
Platelets (× 109/L)	162 (64, 230)	415 (167, 577)	0.007
TB (mg/dL)	2.58 (1.6, 6.7)	3.84 (1.59, 8.27)	0.56
DB (mg/dL)	1.3 (0.71, 4.1)	2.15 (1.08, 4.14)	0.59
AST (U/L)	198 (116, 287)	124.5 (90.75, 238)	0.29
ALT (U/L)	120 (64, 201)	64.5 (37.25, 118.25)	0.06
ALP (U/L)	318 (280, 550)	296 (205.25, 384)	0.15
GGT (U/L)	171 (94, 450)	38 (17, 148.5)	0.007
Prothrombin time	76 (57.5, 100)	100 (88, 100)	0.12
INR	1.27 (1, 1.58)	1.04 (0.97, 1.11)	0.10
Bile acids (µmol/L)	139.5 (33.4, 174.2)	206 (80, 335)	0.24
At last visit
TB (mg/dL)	3.84 (0.94, 15.09)	0.42 (0.28, 2.65)	0.003
DB (mg/dL)	1.87 (0.33, 8.36)	0.09 (0.09, 1.9)	0.007
AST (U/L)	247 (106.7, 462.2)	41 (35.2, 110.2)	0.004
ALT (U/L)	131 (53.5, 140.5)	33 (25.4, 55.5)	0.003
ALP (U/L)	329 (176, 719)	265 (169.5, 461)	0.61
GGT (U/L)	146 (95, 310)	11 (10.25, 13.5)	0.003
INR	1.20 (1.08, 1.69)	1.02 (1, 1.16)	0.01
Total duration of follow up in months	28.5 (3.7, 59)	23 (11.7, 60)	0.61
Outcomes	31.3%	20%	0.66
Progressive disease (death, decompensated disease, uncorrectable coagulopathy at last follow-up)	68.8%	20%	0.01
Mortality	31.3%	20%	0.34

Mann-Whitney U test was applied for non-parametric quantitative variables, and χ²/Fisher's exact test was applied for qualitative variables. ALP: Alkaline phosphatase; AST: Aspartate aminotransferse; ALT: Alanine aminotransferse; DB: Direct bilirubin; GGT: Gamma-glutamyltransferase; HET: Heterozygous; INR: International normalised ratio; TB: Total bilirubin.