TABLE 1.

Genetic and clinical findings in 7 patients with USP53 deficiency

Patient	1	2	3	4	5	6	7
USP53 variant	Deletion of first coding exon	Deletion of first coding exon	Deletion of first coding exon	c.145-11_167del	c.145-11_167del	c.725C>T	c.510delA
Predicted effect	Deletion	Deletion	Deletion	Deletion	Deletion	p.(Pro242Leu)	p.(Ser171ArgfsTer62)
Zygosity	Homozygous	Homozygous	Homozygous	Homozygous	Homozygous	Homozygous	Homozygous
Sex	Female	Male	Female	Female	Male	Male	Male
Ethnicity	Turkish	Turkish	Turkish	Middle Eastern	Middle Eastern	North African	South Asian
Onset of cholestasis	3 months, recurred at 11 months and 6 years	2 months	5 months, approximately 18 and 21 months	7 years, plus gallstones	Neonatal then at 2, 3, and 13 years	15, 16, and 18 years	Approximately 4 years
Earliest available biochemistry documenting cholestasis
Age	3 months	2 months	7 months	N/A	13 years	15 years	21 years
TB/DB, mg/dL	6.6/6.1	5.2/3.8	18.4/14.6	NK	3.9/1.9	3.4/-	6.3/2.8
ALT/AST, U/L	−/163	169/222	61/103	NK	22/38	78/74	84/46
GGT, U/L	41	62	46	“Normal”	35	25	34
TBA, μmol/L	219	ND	ND	NK	37	ND	15
Audiometry								Normal	Normal	Normal	NK	NK	ND	NK
Liver and spleen USS								Liver normal Spleen 12.5 cm @11.5 years (enlarged)	Liver normal Spleen 10.2 cm @8.5 years ULN	Liver normal Spleen 9.8 cm @2 years (enlarged)	Both normal @ 10 years	Liver normal Spleen 10.5 cm @14 years (enlarged for weight)	Liver normal Spleen 15.5 cm @16 years (enlarged)	Liver normal, GB wall thickened, contains sludge Spleen normal @ 20 years
Last follow-up
Age	11 years	8 years	2 years	10 years	13 years	18 years	21 years
Medication	None	None	Rifampicin, UDCA. Relapses off Rifampicin	UDCA	Rifampicin	None	Rifampicin, UDCA and cholestyramine
TB, mg/dL	0.3	0.1	0.1	0.6	1.2	6.4	As above
ALT, U/L	40	48	40	47	17	50
TBA, μmol/L	7	6	ND	ND	35	ND

ALT = alanine aminotransferase; AST = aspartate aminotransferase; DB = direct bilirubin; GB = gall bladder; GGT = gamma-glutamyl transpeptidase; ND = not done; NK = not known; TB = total bilirubin; TBA = total bile acids; UDCA = ursodeoxycholic acid; ULN = upper limit of normal; USS = ultrasound scan. All USP53 variant positions are annotated on transcript: NM_019050.2.