Biallelic CYP24A1 variants presenting during pregnancy: clinical and biochemical phenotypes
Introduction: Inactivating mutations in CYP24A1, encoding vitamin D-24-hydroxylase, can lead to an accumulation of active vitamin D metabolites and consequent hypercalcaemia. Patient (infantile and adult) presentation is varied and includes mild-severe hypercalcaemia, hypercalciuria, nephrocalcinosi...
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| Format: | Article |
| Language: | English |
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Bioscientifica
2020-06-01
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| Series: | Endocrine Connections |
| Subjects: | |
| Online Access: | https://ec.bioscientifica.com/view/journals/ec/9/6/EC-20-0150.xml |
| _version_ | 1818751599947808768 |
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| author | Tomás P Griffin Caroline M Joyce Sumaya Alkanderi Liam M Blake Derek T O’Keeffe Delia Bogdanet Md Nahidul Islam Michael C Dennedy John E Gillan John J Morrison Timothy O’Brien John A Sayer Marcia Bell Paula M O’Shea |
| author_facet | Tomás P Griffin Caroline M Joyce Sumaya Alkanderi Liam M Blake Derek T O’Keeffe Delia Bogdanet Md Nahidul Islam Michael C Dennedy John E Gillan John J Morrison Timothy O’Brien John A Sayer Marcia Bell Paula M O’Shea |
| author_sort | Tomás P Griffin |
| collection | DOAJ |
| description | Introduction: Inactivating mutations in CYP24A1, encoding vitamin D-24-hydroxylase, can lead to an accumulation of active vitamin D metabolites and consequent hypercalcaemia. Patient (infantile and adult) presentation is varied and includes mild-severe hypercalcaemia, hypercalciuria, nephrocalcinosis and nephrolithiasis. This study aimed to characterize the clinical and biochemical phenotypes of a family with two CYP24A1 missense variants.
Methods: The proband and seven family members underwent detailed clinical and biochemical evaluation. Laboratory measurements included serum calcium, intact parathyroid hormone (iPTH), vitamin D metabolites and urine calcium and creatinine.
Results: The proband presented during the second trimester of a planned pregnancy with flu-like symptoms. Laboratory tests showed elevated adjusted cal cium of 3.27 (upper reference limit (URL: 2.30) mmol/L), suppressed iPTH (<6 ng/L), elevated 25(OH)D (264 (URL: 55) nmol/L) and elevated 1,25(OH)D (293 (URL: <280) pmol/L). Ionized calcium was 1.55 (URL: 1.28) mmol/L. Sanger sequencing revealed two heterozygous missense variants in the CYP24A1: p.(Arg439Cys), R439C and p.(Trp275Arg), W275R. The proband’s brother and sister had the same genotype. The brother had intermittent hypercalcaemia and hypervitaminosis D. Only the sister had a history of nephrolithiasis. The proband’s daughter and two nephews were heterozygous for the R439C variant. The proband and her brother frequently had elevated 25(OH)D:24,25(OH)2D ratios (>50) during follow-up.
Conclusions: W275R is a new pathogenic CYP24A1 mutation in compound heterozygotic form with R439C in this family. |
| first_indexed | 2024-12-18T04:38:08Z |
| format | Article |
| id | doaj.art-fffa229a24554561a6d9666239b8bf10 |
| institution | Directory Open Access Journal |
| issn | 2049-3614 2049-3614 |
| language | English |
| last_indexed | 2024-12-18T04:38:08Z |
| publishDate | 2020-06-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-fffa229a24554561a6d9666239b8bf102022-12-21T21:20:48ZengBioscientificaEndocrine Connections2049-36142049-36142020-06-0196530541https://doi.org/10.1530/EC-20-0150Biallelic CYP24A1 variants presenting during pregnancy: clinical and biochemical phenotypesTomás P Griffin0Caroline M Joyce1Sumaya Alkanderi2Liam M Blake3Derek T O’Keeffe4Delia Bogdanet5Md Nahidul Islam6Michael C Dennedy7John E Gillan8John J Morrison9Timothy O’Brien10John A Sayer11Marcia Bell12Paula M O’Shea13Centre for Endocrinology, Diabetes and Metabolism, Saolta University Health Care Group (SUHCG), Galway University Hospitals (GUH), Galway, Ireland; Regenerative Medicine Institute at CÚRAM SFI Research Centre, School of Medicine, National University of Ireland Galway (NUIG), Galway, IrelandDepartment of Clinical Biochemistry, Cork University Hospital, Cork, IrelandTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UKDepartment of Clinical Biochemistry, SUHCG, GUH, Galway, IrelandCentre for Endocrinology, Diabetes and Metabolism, Saolta University Health Care Group (SUHCG), Galway University Hospitals (GUH), Galway, IrelandCentre for Endocrinology, Diabetes and Metabolism, Saolta University Health Care Group (SUHCG), Galway University Hospitals (GUH), Galway, IrelandRegenerative Medicine Institute at CÚRAM SFI Research Centre, School of Medicine, National University of Ireland Galway (NUIG), Galway, Ireland; Department of Clinical Biochemistry, SUHCG, GUH, Galway, IrelandCentre for Endocrinology, Diabetes and Metabolism, Saolta University Health Care Group (SUHCG), Galway University Hospitals (GUH), Galway, Ireland; Lambe Institute for Translational Research, School of Medicine, NUIG, Galway, IrelandDepartment of Histopathology, SUHCG, GUH, Galway, IrelandDepartment of Obstetrics and Gynaecology, SUHCG, GUH, Galway, IrelandCentre for Endocrinology, Diabetes and Metabolism, Saolta University Health Care Group (SUHCG), Galway University Hospitals (GUH), Galway, Ireland; Regenerative Medicine Institute at CÚRAM SFI Research Centre, School of Medicine, National University of Ireland Galway (NUIG), Galway, IrelandTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Newcastle upon Tyne NHS Hospitals Foundation Trust, Newcastle upon Tyne, UK; NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne, UKCentre for Endocrinology, Diabetes and Metabolism, Saolta University Health Care Group (SUHCG), Galway University Hospitals (GUH), Galway, IrelandDepartment of Clinical Biochemistry, SUHCG, GUH, Galway, IrelandIntroduction: Inactivating mutations in CYP24A1, encoding vitamin D-24-hydroxylase, can lead to an accumulation of active vitamin D metabolites and consequent hypercalcaemia. Patient (infantile and adult) presentation is varied and includes mild-severe hypercalcaemia, hypercalciuria, nephrocalcinosis and nephrolithiasis. This study aimed to characterize the clinical and biochemical phenotypes of a family with two CYP24A1 missense variants. Methods: The proband and seven family members underwent detailed clinical and biochemical evaluation. Laboratory measurements included serum calcium, intact parathyroid hormone (iPTH), vitamin D metabolites and urine calcium and creatinine. Results: The proband presented during the second trimester of a planned pregnancy with flu-like symptoms. Laboratory tests showed elevated adjusted cal cium of 3.27 (upper reference limit (URL: 2.30) mmol/L), suppressed iPTH (<6 ng/L), elevated 25(OH)D (264 (URL: 55) nmol/L) and elevated 1,25(OH)D (293 (URL: <280) pmol/L). Ionized calcium was 1.55 (URL: 1.28) mmol/L. Sanger sequencing revealed two heterozygous missense variants in the CYP24A1: p.(Arg439Cys), R439C and p.(Trp275Arg), W275R. The proband’s brother and sister had the same genotype. The brother had intermittent hypercalcaemia and hypervitaminosis D. Only the sister had a history of nephrolithiasis. The proband’s daughter and two nephews were heterozygous for the R439C variant. The proband and her brother frequently had elevated 25(OH)D:24,25(OH)2D ratios (>50) during follow-up. Conclusions: W275R is a new pathogenic CYP24A1 mutation in compound heterozygotic form with R439C in this family.https://ec.bioscientifica.com/view/journals/ec/9/6/EC-20-0150.xmlvitamin dcyp24a1 mutationhypercalcaemiahypervitaminosis dgenetic mutationphenotype |
| spellingShingle | Tomás P Griffin Caroline M Joyce Sumaya Alkanderi Liam M Blake Derek T O’Keeffe Delia Bogdanet Md Nahidul Islam Michael C Dennedy John E Gillan John J Morrison Timothy O’Brien John A Sayer Marcia Bell Paula M O’Shea Biallelic CYP24A1 variants presenting during pregnancy: clinical and biochemical phenotypes Endocrine Connections vitamin d cyp24a1 mutation hypercalcaemia hypervitaminosis d genetic mutation phenotype |
| title | Biallelic CYP24A1 variants presenting during pregnancy: clinical and biochemical phenotypes |
| title_full | Biallelic CYP24A1 variants presenting during pregnancy: clinical and biochemical phenotypes |
| title_fullStr | Biallelic CYP24A1 variants presenting during pregnancy: clinical and biochemical phenotypes |
| title_full_unstemmed | Biallelic CYP24A1 variants presenting during pregnancy: clinical and biochemical phenotypes |
| title_short | Biallelic CYP24A1 variants presenting during pregnancy: clinical and biochemical phenotypes |
| title_sort | biallelic cyp24a1 variants presenting during pregnancy clinical and biochemical phenotypes |
| topic | vitamin d cyp24a1 mutation hypercalcaemia hypervitaminosis d genetic mutation phenotype |
| url | https://ec.bioscientifica.com/view/journals/ec/9/6/EC-20-0150.xml |
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