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Table 2 Patients’ characteristics of subjects with HNF1β mutations presenting with neonatal cholestasis

From: Not only Alagille syndrome. Syndromic paucity of interlobular bile ducts secondary to HNF1β deficiency: a case report and literature review

Sex/origin GW/BW g (DS)

Liver involvement

Liver biopsy

Renal function and ultrasound

Pancreatic involvement

Growth

Urogenital malformations/cognitive impairement

HNF1β mutation

Follow-up duration

Reference

♂/Japan

39/2390 (−2.26)

- neonatal cholestasis, acholic stools

- no abnormality of extrahepatic bile ducts at explorative surgery

- cholestasis resolution at 9-month follow-up with a persistent mild transaminases alteration

- transient hypercholesterolemia

PILBD, marked cholestasis

- multiple bilateral cysts (right, four 1–2 cm diameter cysts, left, one 1 cm diameter cyst)

- mild chronic renal insufficiency

diabetes requiring insulin therapy at 13 years of age (polyuria and polydipsia, mild metabolic acidosis)

NA

absent/ mild

c.457C > A, p.H135N (missense mutation in exon 2, de novo or paternal: history of liver dysfunction and renal insufficiency in his paternal family)

13 years

Kitanaka S 2004 [9]

♂/Belgium (Sardinian origin)

37/1520 (−3.46)

- neonatal cholestasis, slightly enlarged liver

- cholestasis resolution at 1- year follow-up with a persistent mild transaminases alteration

- 3 episodes of cholangitis

- high triglyceridemia (300 mg/dL)

PILBD, severe biliary stasis, slight periportal fibrosis

- left kidney agenesis, enlarged and hyperechogenic right kidney, multiple cortical cysts

- progressive chronic renal insufficiency from 19 months

- diabetes requiring insulin therapy at 5 years of age without ketoacidosis

- pancreatic atrophy with progressive exocrine pancreatic deficiency requiring enzyme substitution from the age of 16 years

final height of 162.1 cm (− 1.86 SD), BMI 19.0 Kg/m2

(− 0.62 SD)

absent/NA

499_504

delGCTCTG

insCCCCT, A167FS

(combination of a deletion and insertion in exon 2, de novo)

18 years

Beckers D 2007 [8]

♂/Germany

35/1780 (− 1.69)

- neonatal cholestasis, acholic stools

- cholestasis resolution at 1 year follow-up with a persistent mild transaminases alteration

- hypercholesterolemia (292 mg/dL) and hypertriglyceridemia (307 mg/dL)

PILBD

- severe malformations of both kidneys (cystic kidney dysplasia and hydronephrosis due to urethral stenosis)

- chronic renal insufficiency

- diabetes requiring insulin therapy at 13 years of age

- pancreatic hypoplasia with progressive exocrine pancreatic deficiency

final height of 133.9 cm (− 6.7 SD), BMI 17.3 Kg/m2 (− 2.1 SD)

inguinal hernia, abdominal testis/delayed psychomotor development

HNF1β deletion exons 1–9, de novo

18 years

Raile K 2009 [6]

♀/Czech Republic

38/2360 (− 1.60)

- neonatal cholestasis, acholic stools

- Kasai portoenterostomy at 32 days of age as extrahepatic bile ducts were not visualized at explorative surgery

- progressive increase in liver function tests, mainly cholestatic

- multiple cysts in the left hepatic lobe (diameter from 2 to 7 mm)

PILBD, cholestasis without signs of bile duct proliferation

- multiple bilateral cortical cysts (maximal diameter 5 mm), prenatally hyperechogenic kidneys

- normal renal function by 2-year follow-up

- mild hypomagnesemia

- pancreatic hypoplasia (absent body and tail) without exocrine pancreatic deficiency

- normoglycaemia by 2-year follow-up

growth along the 3rd centile

absent/absent

1698 kb deletion including HNF1β, de novo

2 years

Kotalova R 2015 [7]

♂/France

35/NA

- neonatal cholestasis without acholic stools

- hepatocellular carcinoma with elevated alpha-fetoprotein levels at 16 months of age requiring liver transplant

- no relapse at 1-year follow-up

- multinodular hepatic tumor and micronodular cirrhosis at the explant

- no information available on PILBD

- renal hyperechogenicity

- transient renal failure

NA

NA

NA/NA

1.5 Mb deletion including HNF1β

2 years

de Leusse C [10]

♂/Italy

38/2600 (− 1.27)

- neonatal cholestasis, hypocholic stools

- persistent cholestasis and pruritus at 18-month follow-up

- hypercholesterolemia (256 mg/dL) and hypertriglyceridemia (120 mg/dL)

PILBD, biliary stasis

- hyperechogenic kidneys, with multiple bilateral cortical cysts (maximum size 2 mm)

- chronic renal insufficiency

initial pancreatic exocrine dysfunction without

pancreatic hypoplasia at US

growth along the 10th centile

absent/absent

c.827G > A, p.R276Q (missense mutation in exon 4, de novo)

18 months

Present report

  1. NA: Information not available, GW: Gestation weeks, BW: Birth weight, PILBD: Paucity of interlobular bile ducts, BMI: Body mass index, US: Ultrasound