Table 1

Familial intrahepatic cholestasis syndromes

Disorder	Chromosome	Gene	Phenotype
Bile acid synthesis disorders
CYP7A1 deficiency	8q21.13	CYP7A1	Hyperlipidaemia, premature coronary and peripheral vascular disease, and premature gallstone disease
CYP7B1 deficiency	8q21.3	CYP7B1	Neonatal cholestasis and cirrhosis
3β-Δ5-C27-Hydroxysteroid oxidoreductase	16p11.2–12	HSD3B7	Neonatal jaundice, fat-soluble vitamin deficiency, and
deficiency			steatorrhoea
Δ4-3-Oxosteroid-5β reductase deficiency	7q32–33	AKR1D1	Intrahepatic cholestasis, jaundice, pale stools, and dark urine
Cerebrotendinous xanthomatosis (CTX)	2q33-qter	CYP27A1	Xanthomatas and cardiovascular problems
2-Methylacyl CoA racemase deficiency	15p13.2–5q11.1	AMACR	Adult-onset sensory motor neuropathy, accumulation of pristanic acids and bile acid intermediates
D-bifunctional protein deficiency	5q2	HSD17B4	Hepatomegaly, developmental defects, hypotonia, and seizures

Bile acid synthesis/tight junction defect
Familial hypercholanaemia	9q12–13	TJP2	Fat malabsorption, vitamin K-deficiency, sometimes cholestasis
(FHCA)	9q22–23	BAAT	and chronic hepatitis

Canalicular transport defects
FIC1 disease	18q21–22	ATP8B1	PFIC1: progressive cholestasis, cirrhosis
			BRIC1: recurrent attacks of cholestasis
			GFC: as in PFIC1
BSEP disease	2q24	ABCB11	PFIC2: progressive cholestasis, cirrhosis
			BRIC2: recurrent attacks of cholestasis
MDR3 disease	7q21	MDR3	PFIC3: extensive bile duct proliferation and fibrosis
Intrahepatic cholestasis of pregnancy	18q21–22, 2q24, 7q21	ATP8B1	Pruritus during third trimester of pregnancy, resolves
(ICP)		ABCB11	after delivery
		MDR3

Other familial intrahepatic cholestasis syndromes
ARC syndrome	15q26.1	VSP33B	Arthrogryposis, renal tubular dysfunction, and cholestasis
Lymphoedema-cholestasis syndrome (LCS)/	15q	?	Neonatal intrahepatic cholestasis and lymphoedema
Aagenaes syndrome
North American Indian childhood	16q22	Cirhin	Neonatal jaundice, biliary cirrhosis
cirrhosis (NAICC)