Phenotypic and genotypic characterization of inflammatory bowel disease in children under six years of age in China

Table 1 Clinical features of dead very-early-onset inflammatory bowel disease patients

Patient	Sex	Age of disease onset	Chief complaints	Perianal diseases	EIMs	Colonoscopy features	Disease cause death	Genetic diagnosis
1	M	Neonate	Diarrhea	Perianal abscess and fistula	Arthritis, oral ulcers	Pancolitis, ulcers and hyperplasia	Lymphoma	NA
2	M	2 mo	Diarrhea, bloody stools	None	None	Proctitis, linear and aphthous ulcers	Suspension of treatment	NA
3	M	1 yr 5 mo	Diarrhea, bloody stools	Perianal abscess	None	Pancolitis and terminal ilium ulcers and hyperplasia	Suspension of treatment	NA
4	F	3 yr 10 mo	Abdominal pain	None	None	Pancolitis, ulcers and cobble stone appearance of colon	Sepsis, multiple organ failure	NA
5	M	4 yr 11 mo	Diarrhea, bloody stools, fever, malnutrition	None	Rash, oral erosion	Pancolitis, erosion, ulcers and multiple hyperplasia lesions	Intestinal bleeding	NA
6	M	2 mo 13 d	Diarrhea, fever	Perianal abscess	None	Proctitis, longitudinal ulcer	Sepsis and shock	CGD

EIMs: Extraintestinal manifestations.

Table 2 General data of very-early-onset inflammatory bowel disease patients

	Monogenic IBD	Nonmonogenic IBD	P value
Patients	9	45
Sex, M/F	8/1	28/17
Median age of disease onset, in mo	1 (0, 72)	19.5 (0, 72)	0.008a
Median age of disease diagnosis, in mo	18 (4, 78)	43.5 (3, 173)	0.021a
Duration before diagnosis, in mo	6 (2, 29)	9 (0, 104)	0.668

^aP < 0.05. IBD: Inflammatory bowel disease.

Table 3 Comparison of clinical features of monogenic and nonmonogenic inflammatory bowel disease groups

	Nonmonogenic IBD	Monogenic IBD	P value
Diagnosis
CD, %	75.0	50.0
IBD-U, %	18.2	40.0
UC, %	6.8	10.0
Abdominal pain, n	25	2	0.142
Diarrhea, n	36	8	1.000
Bloody stools, n	26	8	0.131
Malnutrition, n	19	5	0.489
Growth failure, n	14	4	0.461
Oral ulcers, n	3	1	0.529
Persistent fever, n	3	0	1.000
Perianal diseases, n	9	7	0.001a
Body weight Z-score	-1.54 (-4.69, 2.20)	-2.04 (-3.66, 0.96)	0.303
Height Z-score	-1.38 (-6.43, 2.51)	-1.76 (-4.92, 0.46)	0.597
WBC, as a109	15.04 ± 1.72	12.53 ± 1.72	0.382
HGB, in g/L	103.02 ± 2.57	106.67 ± 5.00	0.496
PLT, as a1012	454.60 ± 28.40	421.89 ± 54.97	0.632
CRP, in mg/L	51.16 ± 8.43	20.22 ± 2.43	0.668
ESR, in mm/h	29.22 ± 4.70	21.00 ± 4.56	0.923
ALB, in g/L	33.80 ± 1.10	36.60 ± 1.77	0.283
Steroid, n	36	6	0.399
Antibiotics, n	29	7	0.484
Mesalazine, n	32	2	0.009a
Immunosuppressants, n	25	8	0.075
Nutrition, n	33	5	0.425
Infliximab, n	14	4	0.461
Surgery, n	6	4	0.050
Death, n	5	1	0.000a

^aP < 0.05. IBD: Inflammatory bowel disease.

Table 4 Clinical characteristics of monogenic very-early-onset inflammatory bowel disease patients

Patient	Sex	Disease onset	Z-score of height	Z-score of body weight	Chief complaints	Others	Disease locations and behavior	Clinical and genetic diagnosis	Intestinal surgery	Treatment	Prognosis
1	M	< 1 mo	0.22	-1.18	Diarrhea, bloody stools	Pyoderma	L2, P, B2B3	CD, IL10RB mutation	Colostomy	Steroid, IFX, thalidomide, 6-MP/MTX/AZA	Remission
2	F	4 mo	-1.76	-0.96	Diarrhea, bloody stools	Pyoderma	L2,L4b, P, B2B3	CD, IL10RA mutation	Intestinal perforation repair, colostomy and J-POUCH	Steroid, mesalazine, IFX, MTX/CsA	Remission
3	M	1 mo+	-0.79	-2.21	Diarrhea, bloody stools	Elevation of ALT	L2, P, B2	CD, IL10RA mutation	None	None	Waiting HSCT
4	M	1 mo+	-3.11	-3.66	Diarrhea, bloody stools	None	L2, P, B1	IBDU, IL10RA mutation	None	Antibiotics	Give up
5	M	11 d	-4.92	-3.38	Diarrhea, bloody stools	NEC	L2,L4b, P, B1	CD, IL10RA mutation	None	Steroids, AZA	Give up
6	M	< 1 mo	0.46	-1.08	Diarrhea, bloody stools	Epilepsy	L2, P, B1	IBDU, CGD	None	None	Remission
7	M	< 1 mo	-0.84	-2.04	Persistent fever	Intestinal malrotation, elevation of ALT	L2, P, B1	IBDU, CGD	None	None	Dead
8	M	9 mo	-4.63	-2.95	Diarrhea, bloody stools	Hepatosplenomegaly	L2, B1	CD, CVID	Intestinal resection and anastomosis	Steroid, 6MP, mesalazine, thalidomide	Partial remission
9	M	5 yr 11 mo	-2.2	-1.57	Abdominal pain, diarrhea, bloody stools	None	L2, L4b	CD, XIAP deficiency	None	DXM, IFX, 6MP/AZA	Remission

6-MP: 6-mercaptopurine; ALT: Alanine aminotransferase; AZA: Azathioprine; CGD: Chronic granulomatous disease; CsA: Cyclosporin A; CVID: Common variable immunodeficiency; HSCT: Hematopoietic stem cell transplantation; IFX: Infliximab; IL10R: Interleukin 10 receptor; MTX: Methotrexate; XIAP: X-linked inhibitor of apoptosis protein.

Table 5 Genetic testing of very-early-onset inflammatory bowel disease patients

Patient	Sex	Age of disease onset	WES/TGPS	Genetic mutation	Location of mutation	Mutation of parents	Homo/Heterozygote	SIFT score/ prediction	Polyphen2 score/ prediction	MutationTaster score/ prediction
1	M	Neonate	Both	IL10RB	Chr21:34660499 c.737G>A p.W246X	Heterozygotic mutation of parents c.737G>A	Homozygote	-	-	6/D
2	F	4 mo	TGPS	IL10RA	Chr11:117860269 c.301C>T p.R101W Chr11:117864125 c.537G>A p.T179T	Heterozygotic mutation of father c.301C>T	Compound heterozygote	0/D	1/D	101/D
						mother c.537G>A		1/T	-	-
3	M	1 mo+	TGPS	IL10RA	Chr11:117860269 c.301C>T p.R101W	Heterozygotic mutation of father c.301C>T	Compound heterozygote	0/D	1/D	101/D
					Chr11:117864058 c.470A>G p.Y157C (rs1027503096)	mother c.470A>G		0.001/D	1/D	194/N
4	M	1 mo+	TGPS	IL10RA	Chr11:117860269 c.301C>T p.R101W	Heterozygotic mutation of parents c.301C>T	Homozygote	0/D	1/D	101/D
5	M	Neonate	TGPS	IL10RA	Chr11:117860269 c.301C>T p.R101W	Heterozygotic mutation of father c.301C>T	Compound heterozygote	0/D	1/D	101/D
					c.350G>A p.R117H (rs199989396)	mother c.350G>A		0.011/D	1/D	29/D
6	M	Neonate	TGPS	CYBB	ChrX:37658209 c.676C>T p.R226X (rs137854592)	Heterozygotic mutation of mother c.676C>T	Hemizygotic mutation	-	-	6/D
7	M	Neonate	TGPS	CYBB	ChrX:37642741 c.142-2A>G splicing	Heterozygotic mutation of mother c.142-2A>G	Hemizygotic mutation	-	-	-
8	M	9 mo	Both	TNFRSF13B	Chr17:16843819 c.452C>T p.P151L (rs200037919)	Heterozygotic mutation of father c.452C>T	Compound heterozygote	0.568/T	0.005/B	98/N
					Chr17:16852132 c.365G>A p.R122Q (rs755343222)	mother c.365G>A		0.485/T	0.136/B	43/N
9	M	5 yr 11 mo	TGPS	XIAP	ChrX:123022501 c.910G>T p.G304X	No mutation in parents	Hemizygotic mutation	-	-	6/D
10	F	5 yr 9 mo	TGPS	IL10RB	Chr21:34652146 c.421G>A p.E141K (rs387907326)	Heterozygotic mutation in father c.421G>A	Heterozygote	0.026/D	0.946/D	56/D
11	F	4 mo	WES	-
12	M	8 mo	WES	-
13	F	3 yr 3 mo	TGPS	-
14	F	4 yr	TGPS	-
15	M	1 yr 10 mo	WES	-
16	F	4 yr 8 mo	WES	-

TGPS: Targeted gene panel sequencing; WES: Whole exome sequencing.