Fat Malabsorption and Ursodeoxycholic Acid Treatment in Children With Reduced Organic Solute Transporter-α ( SLC51A ) Expression.

Autor: Tronstad RR; Department of Pediatrics and Adolescent Medicine, Haukeland University Hospital, Bergen, Norway., Berland S; Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway., Tjora E; Department of Pediatrics and Adolescent Medicine, Haukeland University Hospital, Bergen, Norway.; Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway., El Jellas K; Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.; Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway., Aukrust I; Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.; Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway., Kristensen K; Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark., Tveitnes D; Department of Pediatrics and Adolescent Medicine, Stavanger University Hospital, Stavanger, Norway., Molven A; Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.; Department of Pathology, Haukeland University Hospital, Bergen, Norway., Marschall HU; Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Rao A; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA., Dawson PA; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA.
Jazyk: angličtina
Zdroj: JPGN reports [JPGN Rep] 2022 Aug; Vol. 3 (3). Date of Electronic Publication: 2022 Jul 25.
DOI: 10.1097/pg9.0000000000000229
Abstrakt: Objectives: A bile acid homeostasis disorder was suspected in 2 siblings and their second cousin who presented in infancy with fat malabsorption, severe fat-soluble vitamin deficiency, rickets, and mild liver involvement. Our aims were to identify the genetic cause, describe the disease, and evaluate the response to ursodeoxycholic acid (UDCA) treatment.
Methods: Whole exome sequencing, immunohistochemistry of duodenal biopsies and candidate variant testing in a cell-based model was performed. Fecal fat excretion, serum bile acids, 7α-hydroxy-4-cholesten-3-one (C4), and fibroblast growth factor 19 (FGF19) were quantified in both siblings on and off UDCA treatment.
Results: A novel homozygous variant of SLC51A , which encodes the bile acid carrier organic solute transporter (OST)-α, was identified in all affected children. OSTα protein expression was readily detected by immunohistochemistry in duodenum of pediatric control subjects but not in the affected siblings. The siblings had low serum levels of bile acids and C4 and high serum levels of FGF19 consistent with repression of hepatic bile acid synthesis. On treatment with UDCA, fecal fat excretion was reduced and serum levels of C4, FGF19, and liver enzymes normalized.
Conclusions: We report an apparent deficiency of OSTα associated with early onset fat malabsorption and mild liver involvement. The clinical presentation partially overlaps previous reports for 3 patients with OSTα or OSTβ deficiency and extends the clinical spectrum associated with loss of SLC51A expression. Our data suggest that repression of hepatic bile acid synthesis contributes to fat malabsorption in OSTα-OSTβ deficiency but can be partly reversed with UDCA treatment.
Databáze: MEDLINE
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