Biallelic variants in the SLC13A1 sulfate transporter gene cause hyposulfatemia with a mild spondylo‐epi‐metaphyseal dysplasia. Issue 1 (3rd October 2022)

• Record Type: Journal Article
• Authors: van de Kamp, Jiddeke M.; Bökenkamp, Arend; Smith, Desiree E. C.; Wamelink, Mirjam M. C.; Jansen, Erwin E. W.; Struys, Eduard A.; Waisfisz, Quinten; Verkleij, Marieke; Hartmann, Michaela F.; Wang, Rong; Wudy, Stefan A.; Paganini, Chiara; Rossi, Antonio; Finken, Martijn J. J.
• Is Part Of: Clinical genetics. Volume 103:Issue 1(2023)
• Page Start: 45
• Page End: 52
• Publication Date: 2022-10-03
• Subjects: acetylcysteine -- autistic disorder -- cholesterol -- chondroitin -- joint diseases -- proteoglycans -- skeletal dysplasia -- sulfation; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.14239
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract: Sulfate is the fourth most abundant anion in human plasma but is not measured in clinical practice and little is known about the consequences of sulfate deficiency. Nevertheless, sulfation plays an essential role in the modulation of numerous compounds, including proteoglycans and steroids. We report the first patient with a homozygous loss‐of‐function variant in the SLC13A1 gene, encoding a renal and intestinal sulfate transporter, which is essential for maintaining plasma sulfate levels. The homozygous (Arg12Ter) variant in SLC13A1 was found by exome sequencing performed in a patient with unexplained skeletal dysplasia. The main clinical features were enlargement of joints and spondylo‐epi‐metaphyseal radiological abnormalities in early childhood, which improved with age. In addition, autistic features were noted. We found profound hyposulfatemia due to complete loss of renal sulfate reabsorption. Cholesterol sulfate was reduced. Intravenous N‐acetylcysteine administration temporarily restored plasma sulfate levels. We conclude that loss of the SLC13A1 gene leads to profound hypersulfaturia and hyposulfatemia, which is mainly associated with abnormal skeletal development, possibly predisposing to degenerative bone and joint disease. The diagnosis might be easily missed and more frequent. Abstract : We describe the first patient with biallelic loss‐of‐function variants in the SLC13A1 gene, encoding a renal and intestinal sulfate transporter. The consequential loss of renal sulfate reabsorption leads to hypersulfaturia and hyposulfatemia which is associated with a mild Spondylo‐Epi‐Metaphyseal skeletal Dysplasia.