ESPE Abstracts (2022) 95 P1-137

1Amsterdam UMC, Amsterdam, Netherlands; 2Justus Liebig University, Giessen, Germany; 3University of Pavia, Pavia, Italy

Introduction: Sulfation is required for the metabolism of numerous compounds, including proteoglycans, steroid hormones, neurotransmitters, toxic chemicals, and drugs like acetaminophen. The sulfate transporter SLC13A1 is responsible for the intestinal absorption and the renal reabsorption of inorganic sulfate, but loss-of-function mutations in this gene have never been described in man. Here, we describe a male with a biallelic loss-of-function variant, i.e., R12X, in the SLC13A1 gene who was followed up until age 14 years.

Methods: Our patient underwent assessment of circulating sulfate level, renal sulfate excretion, sulfate loading (using intravenous N-acetylcysteine), and the degree of sulfation of various compounds.

Results: Our patient presented at age 7 months with prominent knees. Skeletal radiographs revealed remarkable generalized widespread skeletal abnormalities, characterized by a spiky widening of all metaphyses, ovoid-shaped vertebral bodies, slightly delayed epiphyseal ossification, irregular tarsal bones, and flared ribs, which gradually improved with age. Neurodevelopment was normal, except for the presence of autistic traits. Linear growth did not deviate from the population reference or from the target height range, although his trunk was relatively short compared to his legs (with a sitting height/height ratio of -2.0 SD score). Pubertal onset was age appropriate. On evaluation, our patient’s plasma sulfate level was low at 44 to 65 (normal range: 322-454) µmol/l, and his fractional sulfate excretion was around 100% (normal range: 13-34%). For comparison, his heterozygous mother had a fractional sulfate excretion of 45%. After the infusion of N-acetylcysteine, our patient’s plasma sulfate level normalized, and 16 hrs later it was returned to baseline. In our patient the proportion of chondroitin sulfate disaccharides in urine was no different from his parents or from controls (92.6% vs. 90.8-96.1% vs. 92.5-94.5%). His serum cholesterol sulfate level was reduced at 443 (normal range: 500-1,236) ng/ml, and his serum steroid sulfate levels were all within the normal range.

Discussion: The homozygous variant R12X of SLC13A1 is characterized by a predominantly skeletal phenotype, which should prompt genetic testing.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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