A novel SLC44A gene variant in a patient with neonatal cholestasis and liver failure

SLC44A1 gene variants (MIM # 618868) are associated with a choline transporter deficiency with a rare autosomal recessive genetic disorder characterized by neurodegeneration, childhood-onset with ataxia, tremor, optic atrophy, and cognitive decline. Variants in the SLC44A1 gene are considered to be...

Full description

Saved in:
Bibliographic Details
Main Authors: Dogan Barut, Emine Burçe Dörtkardeşler, Miray Karakoyun, Ebru Canda, Huseyin Onay, Sema Aydogdu
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Molecular Genetics and Metabolism Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2214426925000199
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850218861523107840
author Dogan Barut
Emine Burçe Dörtkardeşler
Miray Karakoyun
Ebru Canda
Huseyin Onay
Sema Aydogdu
author_facet Dogan Barut
Emine Burçe Dörtkardeşler
Miray Karakoyun
Ebru Canda
Huseyin Onay
Sema Aydogdu
author_sort Dogan Barut
collection DOAJ
description SLC44A1 gene variants (MIM # 618868) are associated with a choline transporter deficiency with a rare autosomal recessive genetic disorder characterized by neurodegeneration, childhood-onset with ataxia, tremor, optic atrophy, and cognitive decline. Variants in the SLC44A1 gene are considered to be responsible for the syndrome. We reported a four-month-old baby with neonatal cholestasis and liver failure, but neurological development and examination were normal. During the patient's initial physical examination, height, weight, and head circumference were < −2 SDS. He was alert, with eye tracking and a smile present, appeared icteric, and exhibited hepatosplenomegaly, with a history of second-degree consanguinity between his parents. The patient showed signs of neonatal jaundice, elevated transaminases, and episodes of hypoglycemia. After excluding biliary atresia, tyrosinemia, and other metabolic diseases, mitochondrial hepatopathy, vascular pathologies, and congenital infectious diseases through all standard examinations for neonatal cholestasis, a genetic analysis test and whole exome analysis were conducted. Molecular analysis of the whole exome revealed a novel inherited mutation, one inherited from each parent. This novel variant in the SLC44A1 gene is c.1632 + 1G > A. A thorough physical examination and laboratory tests should be conducted for patients presenting with neonatal cholestasis. Subsequently, whole exome analysis from the parents identified the same mutation as heterozygous c.1632 + 1G > A in the SLC44A1 gene. Genetic examinations should be considered in patients whose cause remains undetermined, particularly when there is a family history. Conclusion: We describe a novel childhood-onset liver failure and metabolic disease caused by choline transporter deficiency with autosomal recessive inheritance.
format Article
id doaj-art-e6e401b9eb254a4b94d2a4e0e1c99acd
institution OA Journals
issn 2214-4269
language English
publishDate 2025-06-01
publisher Elsevier
record_format Article
series Molecular Genetics and Metabolism Reports
spelling doaj-art-e6e401b9eb254a4b94d2a4e0e1c99acd2025-08-20T02:07:34ZengElsevierMolecular Genetics and Metabolism Reports2214-42692025-06-014310120410.1016/j.ymgmr.2025.101204A novel SLC44A gene variant in a patient with neonatal cholestasis and liver failureDogan Barut0Emine Burçe Dörtkardeşler1Miray Karakoyun2Ebru Canda3Huseyin Onay4Sema Aydogdu5Medical School of Ege University, Division of Gastroenterology, Hepatology and Nutrition Disease, Department of Pediatrics, Izmir, TurkeyDepartment of General Pediatrics, Faculty of Medicine, Childrens' Hospital, Ege University, Bornova, Izmir, Turkey.Medical School of Ege University, Division of Gastroenterology, Hepatology and Nutrition Disease, Department of Pediatrics, Izmir, Turkey; Corresponding author at: Medical School of Ege University, Division of Gastroenterology, Hepatology and Nutrition Disease, Department of Pediatrics, Bornova, Izmir 35100, Turkey.Medical School of Ege University, Division of Pediatric Metabolism and Nutrition, Department of Pediatrics, Izmir, TurkeyMedical Genetics, Multigen Genetic Diseases Diagnosis Center, Izmir, TurkeyMedical School of Ege University, Division of Gastroenterology, Hepatology and Nutrition Disease, Department of Pediatrics, Izmir, TurkeySLC44A1 gene variants (MIM # 618868) are associated with a choline transporter deficiency with a rare autosomal recessive genetic disorder characterized by neurodegeneration, childhood-onset with ataxia, tremor, optic atrophy, and cognitive decline. Variants in the SLC44A1 gene are considered to be responsible for the syndrome. We reported a four-month-old baby with neonatal cholestasis and liver failure, but neurological development and examination were normal. During the patient's initial physical examination, height, weight, and head circumference were < −2 SDS. He was alert, with eye tracking and a smile present, appeared icteric, and exhibited hepatosplenomegaly, with a history of second-degree consanguinity between his parents. The patient showed signs of neonatal jaundice, elevated transaminases, and episodes of hypoglycemia. After excluding biliary atresia, tyrosinemia, and other metabolic diseases, mitochondrial hepatopathy, vascular pathologies, and congenital infectious diseases through all standard examinations for neonatal cholestasis, a genetic analysis test and whole exome analysis were conducted. Molecular analysis of the whole exome revealed a novel inherited mutation, one inherited from each parent. This novel variant in the SLC44A1 gene is c.1632 + 1G > A. A thorough physical examination and laboratory tests should be conducted for patients presenting with neonatal cholestasis. Subsequently, whole exome analysis from the parents identified the same mutation as heterozygous c.1632 + 1G > A in the SLC44A1 gene. Genetic examinations should be considered in patients whose cause remains undetermined, particularly when there is a family history. Conclusion: We describe a novel childhood-onset liver failure and metabolic disease caused by choline transporter deficiency with autosomal recessive inheritance.http://www.sciencedirect.com/science/article/pii/S2214426925000199Choline transporter deficiencyNeonatal cholestasisLiver failure
spellingShingle Dogan Barut
Emine Burçe Dörtkardeşler
Miray Karakoyun
Ebru Canda
Huseyin Onay
Sema Aydogdu
A novel SLC44A gene variant in a patient with neonatal cholestasis and liver failure
Molecular Genetics and Metabolism Reports
Choline transporter deficiency
Neonatal cholestasis
Liver failure
title A novel SLC44A gene variant in a patient with neonatal cholestasis and liver failure
title_full A novel SLC44A gene variant in a patient with neonatal cholestasis and liver failure
title_fullStr A novel SLC44A gene variant in a patient with neonatal cholestasis and liver failure
title_full_unstemmed A novel SLC44A gene variant in a patient with neonatal cholestasis and liver failure
title_short A novel SLC44A gene variant in a patient with neonatal cholestasis and liver failure
title_sort novel slc44a gene variant in a patient with neonatal cholestasis and liver failure
topic Choline transporter deficiency
Neonatal cholestasis
Liver failure
url http://www.sciencedirect.com/science/article/pii/S2214426925000199
work_keys_str_mv AT doganbarut anovelslc44agenevariantinapatientwithneonatalcholestasisandliverfailure
AT emineburcedortkardesler anovelslc44agenevariantinapatientwithneonatalcholestasisandliverfailure
AT miraykarakoyun anovelslc44agenevariantinapatientwithneonatalcholestasisandliverfailure
AT ebrucanda anovelslc44agenevariantinapatientwithneonatalcholestasisandliverfailure
AT huseyinonay anovelslc44agenevariantinapatientwithneonatalcholestasisandliverfailure
AT semaaydogdu anovelslc44agenevariantinapatientwithneonatalcholestasisandliverfailure
AT doganbarut novelslc44agenevariantinapatientwithneonatalcholestasisandliverfailure
AT emineburcedortkardesler novelslc44agenevariantinapatientwithneonatalcholestasisandliverfailure
AT miraykarakoyun novelslc44agenevariantinapatientwithneonatalcholestasisandliverfailure
AT ebrucanda novelslc44agenevariantinapatientwithneonatalcholestasisandliverfailure
AT huseyinonay novelslc44agenevariantinapatientwithneonatalcholestasisandliverfailure
AT semaaydogdu novelslc44agenevariantinapatientwithneonatalcholestasisandliverfailure