ESPN 53rd Annual Meeting

ESPN 2021


 
First description of a case of hyposulfatemic hypersulfaturia caused by a homozygous variant in the SLC13A1 gene
AREND BOKENKAMP 1 MARTIJN FINKEN 1 JIDDEKE VAN DER KAMP 2

1- EMMA CHILDRENS HOSPITAL, AMSTERDAM UMC
2- DEPARTMENT OF CLINICAL GENETICS, AMSTERDAM UMC
 
Abstract:

Background:

Sulfate is an important mineral for cartilage metabolism and hepatic detoxification. Like other ions, sulfate is absorbed via dedicated transporters in the gut and in the proximal tubule. As sulfate is not commonly measured in clinical medicine, sulfate deficiency is not recognized and little is known on the phenotype of sulfate deficiency. This is the first report describing hyposulfatemic hypersulfaturia caused by a homozygous nonsense variant in the SLC13A1 gene, encoding the sodium-sulfate cotransporter, which is responsible for intestinal and renal sulfate (re)absorption.

Case description:

The boy presented at 4 months with enlargement of the knees. X-ray revealed spiky widening of all metaphyses, ovoid-shaped vertebral bodies, slightly delayed epiphyseal ossification, irregular tarsal bones and flared ribs, which improved over the years. At the age of 11 years, he has broad knees and elbows, winged scapulae, a relatively shorter trunk with reduced movement of the lumbar spine and knees.  He has a normal cognitive development, and no kidney or liver dysfunction. 

Trio-based Whole Exome Sequencing showed a homozygous g.122839967G>A (Chr7(GRCh37)), c.34C>T, p.(Arg12*) variant in SLC13A1

Plasma sulfate concentrations were consistently diminished (27-70 µmol/l; N 166-383), fractional excretion of sulfate was elevated to 89% (N 13-34). The heterozygous parents had an intermediate phenotype (sulfate concentrations 58 and 93 µmol/l, fractional excretions 28 and 49%, respectively). As sulfate is critical for paracetamol elimination, we performed an 8-hour iv sulfate loading test with 225 mg/kg acetylcysteine in analogy to the treatment of paracetamol intoxication. This led to a transient normalization of sulfate (max 349 µmol/l), which returned to baseline after 24 hours. 

Conclusion:

Hyposulfatemic hypersulfaturia due to a homozygous variant in the SLC13A1 gene manifests with a distinct skeletal phenotype probably due to abnormal cartilage metabolism that improves with age. Drugs metabolized by sulfation should be avoided, in case of intoxication plasma sulfate can be normalized transiently with high-dose acetylcysteine.