Case Report: Novel Mutation Associated With Hypophosphatemic Kidney Stones and Osteoporosis

Researcher examining genetic test results
Researcher viewing results of a genetic test on a digital tablet.
In this case report, the researchers identified a novel mutation associated with a diagnosis of hypophosphatemic kidney stones and osteoporosis.

Researchers identified a novel autosomal dominant mutation in the solute carrier family 34 member 1 (SCL34A1) gene associated with hypophosphatemic kidney stones and osteoporosis, according to a case report published in Journal of International Medical Research.

A 38-year-old Chinese woman presented with progressive weakness and pain in her lower limbs. Physical examination identified bilateral rib pain and reduced muscle strength in both legs. The woman had no history of any chronic disease or long-term use of any medications. Her mother had a femoral neck fracture associated with a fall when she was aged 45 years and a necrotic femoral head when she was aged 58 years, for which she had surgery.

Blood phosphorus levels were significantly reduced in both the patient (range, 4.86-16.2 mg/dL) and her mother (range, 0.64-14.22 mg/dL); normal range was 17.46 to 28.8 mg/dL. Urinary phosphorous levels were also reduced in both the patient and her mother (ranges, 177.48-347.4 mg/dL/24 hours and 156.6-329.4 mg/dL/24 hours, respectively; normal range, 174.6-756.0 mg/dL/24 hours). Blood, routine urine tests, and urinary calcium levels were normal in both women.

Color ultrasound indicated stones in the left kidney of both the patient and her mother. A whole body computed tomography scan of the patient revealed abnormally active bone mineral metabolism in the joints of the knee, hip, shoulder, and elbow, which resulted in a diagnosis of systemic metabolic bone disease. Magnetic resonance imaging identified a decreased bone signal in the lumbar spine, and digital radiography revealed cervical bone and lumbar vertebrae hyperplasia and osteoporosis in the hands and feet, which was confirmed by dual-energy x-ray absorption.

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Whole exon sequencing identified a mutation in the 13th exon of SLC34A1, which was suspected to be causative of disease. The c.1753 T>C substitution resulted in a serine-to-proline amino acid substation in the protein at position 585, which was predicted to decrease phosphate uptake. This mutation had not been previously reported in the Exome Aggregation Consortium browser from the Broad Institute. The patient’s mother, but not father, also encoded the same mutation.

Based on these findings, the patient was diagnosed with hypophosphatemic kidney stones with osteoporosis. She was given 4 mL of 253 g of disodium hydrogen phosphate and 126 g of potassium dihydrogen phosphate dissolved in 1 L of water every 5 hours and calcitriol (0.5 µg/d). At 1 month, the patient experienced bone pain relief and normalization of blood calcium levels. After 2 months, blood phosphorous levels increased to 16.2 mg/dL and the patient was able to walk slowly and independently. Blood phosphorous levels normalized after 4 months.

“[H]ypophosphatemic kidney stones and osteoporosis can be diagnosed by genetic analysis, which would reduce the rate of misdiagnosis,” the investigators concluded. They also noted that, “in cases of systemic bone pain, fractures, and other symptoms and when the examination suggests hypophosphatemia and SLC34A1 mutation, hypophosphatemic kidney stones and osteoporosis should be considered when there is no notable improvement in symptoms following calcium supplementation.”


Ma Y, Lv H, Wang J, Tan J. Heterozygous mutation of SLC34A1 in patients with hypophosphatemic kidney stones and osteoporosis: a case report. J Int Med Res. 2020;48(3):300060519896146.

This article originally appeared on Rheumatology Advisor