GENETIC SULFATE WASTING, A MONOGENIC CAUSE OF SEVERE INTERVERTEBRAL DISC HEIGHT LOSS

Abstract

INTRODUCTION

Loss of function SLC13A1 variants cause failure to reabsorb sulfate in proximal tubule, reduced serum sulfate, and intervertebral disc disease via glycosaminoglycan abnormalities. A rheumatology patient was found to be homozygous for SCL13A1, explaining an extraordinary spinal disc loss phenotype.

OBJECTIVE

To define intervertebral disc heights and measure sulfate levels and excretion.

METHODS

The homozygote is a 45-year-old female who was only 14 when her already severe degenerative disc disease necessitated her first lumbar laminectomy, with a second performed 4 years later. Her lumbar and thoracic range of motion is greatly reduced. She suffers from severe back pain. Whole genome sequencing identified a stop-gain variant on chromosome 7 at ex.2 c.34C>T p. (Arg12Ter). We measured her radiographic intervertebral disc heights to compare with matched reference values from other studies and older controls from previous Cambridge studies, with 3D reconstructions given the extraordinary disc loss phenotype. The homozygote has a decreased plasma sulfate compared to reference values (149 vs225-494μmol/l). Her urine sulfate is high at 2086umol/l for plasma level. Sulfate excretion rate is excessive 1605mmol/mol creatinine (ref. 444-5431mmol/mol)

RESULTS

Radiographic measurements showed widespread loss of disc height. The proband's brother is also under our care for multiple musculoskeletal (MSK) problems; he is heterozygous for SLC13A1 but has normal disc heights.

CONCLUSIONS

How renal sulphate wasting results in intervertebral disc degeneration in SLC13A1 homozygotes is unclear. Studying such patients might provide an avenue for therapeutic intervention to target widespread disc disease.