Congenital disorder of glycosylation caused by mutation of ATP6AP1 gene (c.1036G>A) in a Chinese infant: A case report

Table 1 Laboratory test results of the patient

Panel	Index/reference range	Result
Liver function	ALT (9-60 U/L)	213
	AST (15-45 U/L)	242
	TBIL (3.40-20.50 μmol/L)	1.60
	IBIL (3.10-14.30 μmol/L)	0.60
	TBA (0.00-10.00 μmol/L)	21.46
	TP (65.0-85.0 g/L)	62.2
	GLO (20.0-40.0 g/L)	11.3
	ALB (40.0-55.0 g/L)	50.9
	GGT (0.0-50.0 U/L)	64.0
	ALP (40-500 U/L)	557
Liver genetic metabolic index	24h-Cu (0.24-0.48 μmol/24 h)	0.03
	CER (180-450 mg/L)	133
	LACT (0.63-2.44 mmol/L)	2.79
	Blood ammonia (18-72 μg/dL)	181
Immunoglobulin	IgG (8.0-18.0 g/L)	4.20
	IgA (0.90-4.50 g/L)	1.30
	IgM (0.84-1.32 g/L)	0.54
Routine blood test	PLT (125-350 × 109/L)	138
Blood lipids	HDL-C (1.03-2.07 mmoL/L)	0.09
	LDL-C (1.0-4.4 mmol/L)	1.74
Cardiac enzymes	CK (10-174 U/L)	94
	CK-MB (0.0-25.0 U/L)	56.0
	LD (109-245 U/L)	331

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TBIL: Total bilirubin; IBIL: Indirect bilirubin; TBA: Total bile acids; TP: Total protein; GLO: Globulin; ALB: Albumin; GGT: Gamma-glutamyl transpeptidase; ALP: Alkaline phosphatase; 24h-Cu: 24-hour urine copper; CER: Ceruloplasmin; LACT: Lactic acid; PLT: Platelets; HDL-C: High-density lipoprotein; LDL-C: Low-density lipoprotein; CK: Creatine kinase; CK-MB: Creatine kinase myocardial band; LD: Lactate dehydrogenase.

Table 2 Results of several follow-up examinations and medications for the child

Age	ALT	AST	IgG	IgA	IgM	Blood ammonia	Medication
8 mo	213	242	4.2	1.3	0.54	181	Glutathione, ursodeoxycholic acid, ornithine monohydrate
9 mo	202	332	3.5	0.1	0.16	74	Glutathione, ​compound glycyrrhizin
11 mo	388	515	-	-	-	-	Glutathione, ​compound glycyrrhizin
12 mo	167	111	3.12	0.37	0.36	142	Glutathione, ​compound glycyrrhizin, ornithine monohydrate
19 mo	128	196	2.16	0.32	0.09	95	Bicyclol, compound glycyrrhizin

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; Ig: Immunoglobulin.

Table 3 Comparison of reported clinical presentations of patients with ATP6AP1-congenital disorders of glycosylation

Family	Case	Initial diagnosis/death age	cDNA mutation	Connective tissue abnormalities	Infections	Neurological symptoms	Hepatosplenomegaly
1[4]	1.1	20 yr	c.1284G>A	Bilateral inguinal hernias	+	-	Hepatomegaly
	1.2	12 yr		Bilateral inguinal hernias	+	+/-	-
	1.3	34 yr		Bilateral inguinal hernias	+	-	-
2[4]	2	14 yr	c.431T>C	NA	+	-	-
3[4]	3.1	8 yr	c.1036G>A	NA	+	+	+
	3.2	Died 4 yr		NA	+	+	+
4[4]	4.1	23 yr	c.1036G>A	NA	+	+	+
	4.2	18 yr		NA	+	+	+
5[4]	5.1	Died 12 mo	c.1036G>A	NA	+	+	+
	5.2	3 yr		NA	+	+	Hepatomegaly
6[4]	6	4 yr	c.938A>G	NA	+	-	Hepatomegaly
7[15]	7	5 mo	c.649T>A	CL, aortic root dilation, diaphragmatic hernia	+	-	+
8[12]	8	10 yr	c.542T>G	CL, joint hypermobility	+	+/-	+
9[13]	9.1	Died 3 mo	c.221T>C	CL	-	-	+
	9.2	Died 11 mo		CL	-	-	+
10[14]	10.1	NA	c.923T>A	Ascending aorta dilation	-	-	+
	10.2	Died 4 mo		Ascending aorta dilation, atrial septal defect	-	-	Hepatomegaly
11[21]	11	1.5 yr	NA	Joint hypermobility	+	-	+
12	12	8 mo	c.1036G>A	-	+	+	+

+: Abnormal; -: Normal; NA: Not available.

Table 4 Comparison of reported ancillary tests in patients with ATP6AP1-congenital disorders of glycosylation

Family	Case	Abnormal liver function	Hypogammaglobulinemia	Low serum copper/ ceruloplasmin	Liver biopsy
1[4]	1.1	+/-	+	+	NA
	1.2	+/-	+	+	NA
	1.3	+/-	+	NA	-
2[4]	2	+/-	+	+	Slight steatosis
3[4]	3.1	+/-	+	+	Fibrosis, steatosis, cirrhosis
	3.2	+/-	+	+	Steatosis, cirrhosis
4[4]	4.1	+	+	+	Micronodular cirrhosis
	4.2	+	+	+	Micronodular cirrhosis
5[4]	5.1	+	+	+	Fibrosis, cirrhosis, steatosis, cholestasis
	5.2	+	+	+	NA
6[4]	6	+	+	+/-	Fibrosis, cirrhosis, steatosis
7[15]	7	+	-	+	Micronodular cirrhosis, steatosis
8[12]	8	+	+	+	NA
9[13]	9.1	+	-	+	Fibrosis, steatosis, cholestasis
	9.2	+	-	+	Fibrosis, steatosis, cholestasis
10[14]	10.1	+	+	+	Fibrosis, steatosis, micronodular cirrhosis
	10.2	+	-	+	Fibrosis, steatosis, micronodular cirrhosis
11[21]	11	+	+	+	Steatosis, cirrhosis
12	12	+	+	+	Chronic hepatitis, nodular cirrhosis

+: Abnormal; -: Normal; NA: Not available.