Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency.
Gastroenterology
; 144(5): 945-955.e6; quiz e14-5, 2013 May.
Article
en En
| MEDLINE
| ID: mdl-23415802
ABSTRACT
BACKGROUND & AIMS:
The final step in bile acid synthesis involves conjugation with glycine and taurine, which promotes a high intraluminal micellar concentration to facilitate lipid absorption. We investigated the clinical, biochemical, molecular, and morphologic features of a genetic defect in bile acid conjugation in 10 pediatric patients with fat-soluble vitamin deficiency, some with growth failure or transient neonatal cholestatic hepatitis.METHODS:
We identified the genetic defect that causes this disorder using mass spectrometry analysis of urine, bile, and serum samples and sequence analysis of the genes encoding bile acid-CoAamino acid N-acyltransferase (BAAT) and bile acid-CoA ligase (SLC27A5).RESULTS:
Levels of urinary bile acids were increased (432 ± 248 µmol/L) and predominantly excreted in unconjugated forms (79.4% ± 3.9%) and as sulfates and glucuronides. Glycine or taurine conjugates were absent in the urine, bile, and serum. Unconjugated bile acids accounted for 95.7% ± 5.8% of the bile acids in duodenal bile, with cholic acid accounting for 82.4% ± 5.5% of the total. Duodenal bile acid concentrations were 12.1 ± 5.9 mmol/L, which is too low for efficient lipid absorption. The biochemical profile was consistent with defective bile acid amidation. Molecular analysis of BAAT confirmed 4 different homozygous mutations in 8 patients tested.CONCLUSIONS:
Based on a study of 10 pediatric patients, genetic defects that disrupt bile acid amidation cause fat-soluble vitamin deficiency and growth failure, indicating the importance of bile acid conjugation in lipid absorption. Some patients developed liver disease with features of a cholangiopathy. These findings indicate that patients with idiopathic neonatal cholestasis or later onset of unexplained fat-soluble vitamin deficiency should be screened for defects in bile acid conjugation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Avitaminosis
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ADN
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Ácidos y Sales Biliares
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Coenzima A Ligasas
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Predisposición Genética a la Enfermedad
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Mutación Missense
Tipo de estudio:
Prognostic_studies
Límite:
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Gastroenterology
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos