Heterozygous mutations of ATP8B1, ABCB11 and ABCB4 cause mild forms of Progressive Familial Intrahepatic Cholestasis in a pediatric cohort
Por:
Beatriz Mínguez Rodríguez, Molera C, Martorell-Sampol L, Romero RG, Rivero GC and Martín-de-Carpi J
Publicada:
1 oct 2022
Ahead of Print:
1 oct 2022
Resumen:
Introduction: Heterozygous defects in genes implicated in Progressive Familial Intrahepatic Cholestasis have been described in milder forms of cholestatic diseases. Our aim is to describe clinical, laboratory and imaging characteristics as well as treatment and outcome of a cohort of pediatric patients with heterozygous mutations in ATP8B1, ABCB11 or ABCB4.
Patients and methods: We present a retrospective descriptive study including pediatric patients with at least one heterozygosis defect in ATP8B1, ABCB11 or ABCB4 diagnosed after a cholestatic episode. Clinical, diagnostic and outcome data were collected including gene analysis (panel of PFIC NextGeneDx (R)).
Results: 7 patients showed a heterozygous mutation: 3 patients in ABCB4, 1 in ABCB11, 2 in ABCB4 and ABCB11 and 1 in ATP8B1. The median onset age was 5.5 years with a median time of follow-up of 6 years. The initial presentation was pruritus followed by asymptomatic hypertransaminasemia and persistent cholestasis. Two patients had family history of gallbladder stones and mild hepatitis. All showed elevated transaminases and bile acids, high gamma glutamyl-transferase (GGT) in 3 and conjugated bilirubin in 2 patients. Liver biopsy showed inflammatory infiltrate or mild fibrosis with normal immunohistochemistry. All patients were treated with ursodeoxycholic acid, two patients requiring the addition of resincholestyramine. During follow-up, 3 patients suffered limited relapses of pruritus. No disease progression was observed.
Conclusion: Heterozygous mutations in genes coding proteins of the hepatocellular transport system can cause cholestatic diseases with great phenotypic variability. The presenceof repeated episodes of hypertransaminasemia or cholestasis after a trigger should force us torule out the presence of these heterozygous mutations in genes involved in CIFP.
Filiaciones:
Beatriz Mínguez Rodríguez:
Department of Gastroenterology, Hepatology and Nutrition. Sant Joan de Déu Hospital, Barcelona, Spain
Molera C:
Department of Gastroenterology, Hepatology and Nutrition. Sant Joan de Déu Hospital, Barcelona, Spain
Martorell-Sampol L:
Department of Genetics. Sant Joan de Déu Hospita, Barcelona, Spain. Electronic address:
Romero RG:
Unit of Paediatric Gastroenterology, Hepatology and Nutrition. Miguel Servet Hospital, Zaragoza, Spain
Rivero GC:
Department of Paediatric Gastroenterology. Nens Hospital of Barcelona, Barcelona, Spain
Martín-de-Carpi J:
Department of Gastroenterology, Hepatology and Nutrition. Sant Joan de Déu Hospital, Barcelona, Spain
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