Alteration of bone microarchitecture in hereditary distal RTA patients with SLC4A1 gene mutation: assessed by HR-pQCT

Context Hereditary distal renal tubular acidosis caused by SLC4A1 gene mutation (SLC4A1-dRTA) is a rare hereditary form of renal tubular acidosis. Rickets or osteomalacia is a common complication of SLC4A1-dRTA and seriously affects patients’ daily lives. However, studies on the bone microstructure in SLC4A1-dRTA are limited. Objective This work aimed to evaluate the bone microstructure of SLC4A1-dRTA patients, compared to age- and sex-matched healthy controls and X-linked hypophosphatemic rickets (XLH) patients. Methods This was a retrospective study of 11 SLC4A1-dRTA patients. Clinical manifestations and biochemical and radiographical examinations were characterized. Bone microstructure was examined in 7 SLC4A1-dRTA patients, 7 healthy controls, and 21 XLH patients using high-resolution peripheral quantitative computed tomography. Results Skeletal symptoms, including fracture, bone pain, and lower limb deformity, were present in 72.7% of SLC4A1-dRTA patients. Short stature was present in 63.6% of the patients. SLC4A1-dRTA patients had significantly lower volumetric bone mineral density in the distal tibia and more severe deteriorated trabecular bone in the distal radius and tibia than healthy controls. SLC4A1-dRTA patients had significantly more severely deteriorated trabecular bone in the distal radius and distal tibia compared to XLH patients. With long-term alkaline therapy, SLC4A1-dRTA patients had alleviated bone pain and increased height. Conclusion Skeletal lesions were common clinical manifestations in SLC4A1-dRTA patients. Compared with XLH, another common type of rickets, SLC4A1-dRTA patients had more severe trabecular bone microstructure damage, further supporting the necessity of early diagnosis and timely treatment of the disease.