Diagnosis of Alagille Syndrome-25 Years of Experience at King's College Hospital

P. Subramaniam; A. Knisely; B. Portmann; S. A. Qureshi; W. A. Aclimandos; J. B. Karani; A. J. Baker

doi:10.1097/MPG.0b013e3181f1572d

Diagnosis of Alagille Syndrome-25 Years of Experience at King's College Hospital

P. Subramaniam, A. Knisely, B. Portmann, S. A. Qureshi, W. A. Aclimandos, J. B. Karani, A. J. Baker^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

89 Citations (Scopus)

Abstract

Objective: The aim of the study was to study the clinical and histological features of Alagille syndrome (AGS) at presentation comparing the value of the various modalities before the implementation of genetic diagnosis.

Patients and Methods: We performed a retrospective analysis of the records of 117 children diagnosed as having AGS after referral to King's College Hospital between 1980 and 2005.

Results: Cholestasis was seen in 104 of 117 (89%), characteristic facies in 91 of 117 (77%), posterior embryotoxon in 72 of 117 (61%), butterfly vertebrae in 44 of 117 (39%), heart disease (most often peripheral pulmonary stenosis) in 107 of 117 (91%), and renal disease in 27 of 117 (23%). Serum cholesterol levels of > 5 mmol/L were seen in 52 of 86 (60.4%). Liver biopsy showed characteristic features of paucity of interlobular bile ducts in 59 of 77 (76.6%) children younger than 16 weeks of age, in 10 of 14 (71.4%) between 16 weeks and 1 year of age, and in 8 of 12 (66.66%) older than 1 year of age. Other biopsy findings were those of nonspecific hepatitis and biliary features. Iminodiacetic acid scans showed no excretion of isotope into the bowel after 24 hours in 21 of 35 (60%), and small/no gallbladder on ultrasound was seen in 29 of 104 (27.8%). Eleven of 117 (9.4%) had a diagnostic laparotomy and operative cholangiography, 2 proceeding to Kasai portoenterostomy before referral to our unit.

Conclusions: Clinical features of AGS are not as consistently informative as suggested in the literature. Hypercholesterolaemia is nonspecific but may be a helpful pointer. Histology is not characteristic in 25%; hepatobiliary iminodiacetic acid scan and ultrasound may suggest a false diagnosis of biliary atresia in 60% and 28%, respectively, supporting the concept that infants with liver disease warrant early referral to a specialist centre. The advent of genetic diagnosis will redefine the syndrome with likely effects on the prognosis of the defined group.

Original language	English
Pages (from-to)	84-89
Number of pages	6
Journal	Journal of Pediatric Gastroenterology and Nutrition
Volume	52
Issue number	1
DOIs	https://doi.org/10.1097/MPG.0b013e3181f1572d
Publication status	Published - Jan 2011

Keywords

Alagille syndrome
cholestasis
diagnosis
paucity
ARTERIOHEPATIC DYSPLASIA
LIVER-TRANSPLANTATION
JAGGED1 GENE
BILE-DUCTS
BILIARY ATRESIA
MUTATIONS
CHOLESTASIS
FREQUENCY
MORBIDITY
CHILDREN

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1097/MPG.0b013e3181f1572d

Cite this

@article{ac1a4678ef204cf4be55b314d16db06a,

title = "Diagnosis of Alagille Syndrome-25 Years of Experience at King's College Hospital",

abstract = "Objective: The aim of the study was to study the clinical and histological features of Alagille syndrome (AGS) at presentation comparing the value of the various modalities before the implementation of genetic diagnosis.Patients and Methods: We performed a retrospective analysis of the records of 117 children diagnosed as having AGS after referral to King's College Hospital between 1980 and 2005.Results: Cholestasis was seen in 104 of 117 (89%), characteristic facies in 91 of 117 (77%), posterior embryotoxon in 72 of 117 (61%), butterfly vertebrae in 44 of 117 (39%), heart disease (most often peripheral pulmonary stenosis) in 107 of 117 (91%), and renal disease in 27 of 117 (23%). Serum cholesterol levels of > 5 mmol/L were seen in 52 of 86 (60.4%). Liver biopsy showed characteristic features of paucity of interlobular bile ducts in 59 of 77 (76.6%) children younger than 16 weeks of age, in 10 of 14 (71.4%) between 16 weeks and 1 year of age, and in 8 of 12 (66.66%) older than 1 year of age. Other biopsy findings were those of nonspecific hepatitis and biliary features. Iminodiacetic acid scans showed no excretion of isotope into the bowel after 24 hours in 21 of 35 (60%), and small/no gallbladder on ultrasound was seen in 29 of 104 (27.8%). Eleven of 117 (9.4%) had a diagnostic laparotomy and operative cholangiography, 2 proceeding to Kasai portoenterostomy before referral to our unit.Conclusions: Clinical features of AGS are not as consistently informative as suggested in the literature. Hypercholesterolaemia is nonspecific but may be a helpful pointer. Histology is not characteristic in 25%; hepatobiliary iminodiacetic acid scan and ultrasound may suggest a false diagnosis of biliary atresia in 60% and 28%, respectively, supporting the concept that infants with liver disease warrant early referral to a specialist centre. The advent of genetic diagnosis will redefine the syndrome with likely effects on the prognosis of the defined group.",

keywords = "Alagille syndrome, cholestasis, diagnosis, paucity, ARTERIOHEPATIC DYSPLASIA, LIVER-TRANSPLANTATION, JAGGED1 GENE, BILE-DUCTS, BILIARY ATRESIA, MUTATIONS, CHOLESTASIS, FREQUENCY, MORBIDITY, CHILDREN",

author = "P. Subramaniam and A. Knisely and B. Portmann and Qureshi, {S. A.} and Aclimandos, {W. A.} and Karani, {J. B.} and Baker, {A. J.}",

year = "2011",

month = jan,

doi = "10.1097/MPG.0b013e3181f1572d",

language = "English",

volume = "52",

pages = "84--89",

journal = "Journal of Pediatric Gastroenterology and Nutrition",

issn = "0277-2116",

publisher = "Lippincott Williams and Wilkins",

number = "1",

}

TY - JOUR

T1 - Diagnosis of Alagille Syndrome-25 Years of Experience at King's College Hospital

AU - Subramaniam, P.

AU - Knisely, A.

AU - Portmann, B.

AU - Qureshi, S. A.

AU - Aclimandos, W. A.

AU - Karani, J. B.

AU - Baker, A. J.

PY - 2011/1

Y1 - 2011/1

N2 - Objective: The aim of the study was to study the clinical and histological features of Alagille syndrome (AGS) at presentation comparing the value of the various modalities before the implementation of genetic diagnosis.Patients and Methods: We performed a retrospective analysis of the records of 117 children diagnosed as having AGS after referral to King's College Hospital between 1980 and 2005.Results: Cholestasis was seen in 104 of 117 (89%), characteristic facies in 91 of 117 (77%), posterior embryotoxon in 72 of 117 (61%), butterfly vertebrae in 44 of 117 (39%), heart disease (most often peripheral pulmonary stenosis) in 107 of 117 (91%), and renal disease in 27 of 117 (23%). Serum cholesterol levels of > 5 mmol/L were seen in 52 of 86 (60.4%). Liver biopsy showed characteristic features of paucity of interlobular bile ducts in 59 of 77 (76.6%) children younger than 16 weeks of age, in 10 of 14 (71.4%) between 16 weeks and 1 year of age, and in 8 of 12 (66.66%) older than 1 year of age. Other biopsy findings were those of nonspecific hepatitis and biliary features. Iminodiacetic acid scans showed no excretion of isotope into the bowel after 24 hours in 21 of 35 (60%), and small/no gallbladder on ultrasound was seen in 29 of 104 (27.8%). Eleven of 117 (9.4%) had a diagnostic laparotomy and operative cholangiography, 2 proceeding to Kasai portoenterostomy before referral to our unit.Conclusions: Clinical features of AGS are not as consistently informative as suggested in the literature. Hypercholesterolaemia is nonspecific but may be a helpful pointer. Histology is not characteristic in 25%; hepatobiliary iminodiacetic acid scan and ultrasound may suggest a false diagnosis of biliary atresia in 60% and 28%, respectively, supporting the concept that infants with liver disease warrant early referral to a specialist centre. The advent of genetic diagnosis will redefine the syndrome with likely effects on the prognosis of the defined group.

AB - Objective: The aim of the study was to study the clinical and histological features of Alagille syndrome (AGS) at presentation comparing the value of the various modalities before the implementation of genetic diagnosis.Patients and Methods: We performed a retrospective analysis of the records of 117 children diagnosed as having AGS after referral to King's College Hospital between 1980 and 2005.Results: Cholestasis was seen in 104 of 117 (89%), characteristic facies in 91 of 117 (77%), posterior embryotoxon in 72 of 117 (61%), butterfly vertebrae in 44 of 117 (39%), heart disease (most often peripheral pulmonary stenosis) in 107 of 117 (91%), and renal disease in 27 of 117 (23%). Serum cholesterol levels of > 5 mmol/L were seen in 52 of 86 (60.4%). Liver biopsy showed characteristic features of paucity of interlobular bile ducts in 59 of 77 (76.6%) children younger than 16 weeks of age, in 10 of 14 (71.4%) between 16 weeks and 1 year of age, and in 8 of 12 (66.66%) older than 1 year of age. Other biopsy findings were those of nonspecific hepatitis and biliary features. Iminodiacetic acid scans showed no excretion of isotope into the bowel after 24 hours in 21 of 35 (60%), and small/no gallbladder on ultrasound was seen in 29 of 104 (27.8%). Eleven of 117 (9.4%) had a diagnostic laparotomy and operative cholangiography, 2 proceeding to Kasai portoenterostomy before referral to our unit.Conclusions: Clinical features of AGS are not as consistently informative as suggested in the literature. Hypercholesterolaemia is nonspecific but may be a helpful pointer. Histology is not characteristic in 25%; hepatobiliary iminodiacetic acid scan and ultrasound may suggest a false diagnosis of biliary atresia in 60% and 28%, respectively, supporting the concept that infants with liver disease warrant early referral to a specialist centre. The advent of genetic diagnosis will redefine the syndrome with likely effects on the prognosis of the defined group.

KW - Alagille syndrome

KW - cholestasis

KW - diagnosis

KW - paucity

KW - ARTERIOHEPATIC DYSPLASIA

KW - LIVER-TRANSPLANTATION

KW - JAGGED1 GENE

KW - BILE-DUCTS

KW - BILIARY ATRESIA

KW - MUTATIONS

KW - CHOLESTASIS

KW - FREQUENCY

KW - MORBIDITY

KW - CHILDREN

U2 - 10.1097/MPG.0b013e3181f1572d

DO - 10.1097/MPG.0b013e3181f1572d

M3 - Article

SN - 0277-2116

VL - 52

SP - 84

EP - 89

JO - Journal of Pediatric Gastroenterology and Nutrition

JF - Journal of Pediatric Gastroenterology and Nutrition

IS - 1

ER -

Diagnosis of Alagille Syndrome-25 Years of Experience at King's College Hospital

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this