CONTEXT: Although AP2S1 has recently been shown to be a causative gene for familial hypocalciuric hypercalcemia type 3 (FHH3), knowledge about FHH3 remains poor. OBJECTIVE: Our objective was to report AP2S1 mutation and effects of low calcium formula in a patient with hypercalcemia and hypercalciuria. PATIENT: This Japanese female infant was found to have hypercalcemia by a routine laboratory test for poor weight gain on breast feeding. At 49 days of age, serum calcium (adjusted by Payne's formula) was 13.1 mg/dL, intact PTH 27 pg/mL, and urinary calcium-to-creatinine ratio 1.29 mg/mg. There was no evidence for hyperparathyroidism, PTHrP-producing neoplasm, and vitamin D excess. These data, except for hypercalciuria, appeared to be consistent with defective calcium-sensing receptor-mediated signaling. With use of low calcium formula containing 2.6 mg/dL of calcium, she showed catch-up growth, and serum calcium was decreased, as was urinary calcium-to-creatinine ratio. Furthermore, feeding with a mixture of low calcium formula and standard formula with a 2:1 ratio maintained serum calcium ∼12 mg/dL without markedly increasing serum PTH. RESULTS: Although no pathologic mutation was detected in CASR or GNA11, a presumably de novo heterozygous mutation (p.Arg15Leu), a previously reported causative mutation for FHH3, was identified in AP2S1 of this patient. CONCLUSIONS: The results imply that lack of hypocalciuria does not necessarily argue against the presence of AP2S1 mutations. The early infantile age of this patient would have played a certain role in the occurrence of hypercalciuria, and low calcium formula is worth attempting in infants with FHH.
CONTEXT: Although AP2S1 has recently been shown to be a causative gene for familial hypocalciuric hypercalcemia type 3 (FHH3), knowledge about FHH3 remains poor. OBJECTIVE: Our objective was to report AP2S1 mutation and effects of low calcium formula in a patient with hypercalcemia and hypercalciuria. PATIENT: This Japanese female infant was found to have hypercalcemia by a routine laboratory test for poor weight gain on breast feeding. At 49 days of age, serum calcium (adjusted by Payne's formula) was 13.1 mg/dL, intact PTH 27 pg/mL, and urinary calcium-to-creatinine ratio 1.29 mg/mg. There was no evidence for hyperparathyroidism, PTHrP-producing neoplasm, and vitamin D excess. These data, except for hypercalciuria, appeared to be consistent with defective calcium-sensing receptor-mediated signaling. With use of low calcium formula containing 2.6 mg/dL of calcium, she showed catch-up growth, and serum calcium was decreased, as was urinary calcium-to-creatinine ratio. Furthermore, feeding with a mixture of low calcium formula and standard formula with a 2:1 ratio maintained serum calcium ∼12 mg/dL without markedly increasing serum PTH. RESULTS: Although no pathologic mutation was detected in CASR or GNA11, a presumably de novo heterozygous mutation (p.Arg15Leu), a previously reported causative mutation for FHH3, was identified in AP2S1 of this patient. CONCLUSIONS: The results imply that lack of hypocalciuria does not necessarily argue against the presence of AP2S1 mutations. The early infantile age of this patient would have played a certain role in the occurrence of hypercalciuria, and low calcium formula is worth attempting in infants with FHH.
Authors: Katie Leach; Fadil M Hannan; Tracy M Josephs; Andrew N Keller; Thor C Møller; Donald T Ward; Enikö Kallay; Rebecca S Mason; Rajesh V Thakker; Daniela Riccardi; Arthur D Conigrave; Hans Bräuner-Osborne Journal: Pharmacol Rev Date: 2020-07 Impact factor: 25.468
Authors: Caroline M Gorvin; Treena Cranston; Fadil M Hannan; Nigel Rust; Asjid Qureshi; M Andrew Nesbit; Rajesh V Thakker Journal: J Bone Miner Res Date: 2016-02-06 Impact factor: 6.741
Authors: Silje Hovden; Marie Louise Jespersen; Peter H Nissen; Per Løgstrup Poulsen; Lars Rolighed; Søren A Ladefoged; Lars Rejnmark Journal: Clin Case Rep Date: 2016-08-18
Authors: Fadil M Hannan; Sarah A Howles; Angela Rogers; Treena Cranston; Caroline M Gorvin; Valerie N Babinsky; Anita A Reed; Clare E Thakker; Detlef Bockenhauer; Rosalind S Brown; John M Connell; Jacqueline Cook; Ken Darzy; Sarah Ehtisham; Una Graham; Tony Hulse; Steven J Hunter; Louise Izatt; Dhavendra Kumar; Malachi J McKenna; John A McKnight; Patrick J Morrison; M Zulf Mughal; Domhnall O'Halloran; Simon H Pearce; Mary E Porteous; Mushtaqur Rahman; Tristan Richardson; Robert Robinson; Isabelle Scheers; Haroon Siddique; William G Van't Hoff; Timothy Wang; Michael P Whyte; M Andrew Nesbit; Rajesh V Thakker Journal: Hum Mol Genet Date: 2015-06-16 Impact factor: 6.150