Background: Hyperphosphataemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive condition in which increased renal phosphate reabsorption is associated with elevated serum phosphate, inappropriately normal or raised PTH and extraosseous calcification. It is caused by mutations in genes related to phosphate metabolism: fibroblast growth factor 23 (FGF23), UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) and Klotho (KL). We present a patient with HFTC and a heterozygous mutation in GALNT3.
Presenting problem: A 9-year Afro Caribbean old girl presented with a hot, swollen, tender mass of her right hip and buttock associated with several months of fatigue and pain. She was previously well and from a non consanguineous union with no family history of renal or skeletal disorders. Examination revealed a 78 cm mass in her right buttock and X-ray and CT imaging demonstrated a large calcified mass in the muscle and subcutaneous fat in the region of the right greater trochanter. Serum phosphate was elevated at 1.83 mmol/l, the fractional excretion of phosphate (FEPO4) was 4.09% with an elevated theoretical tubular maximum of phosphate reabsorption of >2.0 mmol/l (NR 0.81.35 mmol/l). Serum creatinine and calcium were within the normal range and serum PTH was inappropriately normal (4.5 pmol/l).
Clinical management: Treatment with sevelamer and acetazolamide resulted in a serum phosphate of 1.6 mmol/l, reduction in pain and increased mobility.
DNA analysis showed no mutations in FGF23 or KL. The patient was heterozygous for a novel missense variant, p.Val267Phe (c.799G>T) in exon 3 of GALNT3. Familial studies revealed that the non affected father also had the same mutation in heterozygous form.
Discussion: HFTC has been described to result from homozygous or compound heterozygous mutations in FGF23, GALNT3 and KL. In this case, it is unclear if the heterozygous GALNT3 missense mutation detected is related to HFTC. Her unaffected father also carries this mutation as do 3.4% of individuals from Sub-Saharan Africa and 3.31% of African Americans. HFTC in this child may be as a result of an autosomal recessive compound heterozygous mutation in which the maternal mutation in GALNT3 remains undetected or due to mutations in a gene related to phosphate metabolism which is as yet unidentified.
22 - 25 Jun 2013