FH, a 36-year-old female of Afghan origin, resident in the UK for 4 years, was referred to the medical services by her obstetrician 9 days postpartum with symptomatic hypocalcaemia. Biochemical investigations confirmed a low corrected calcium (1.43 mmol/l, 2.12.6 mmol/l), elevated phosphate (1.76, 0.81.45 mmol/l) and alkaline phosphatase (156, 30130 U/l). Twenty-five hydroxy vitamin D was 16 nmol/l (15100) with elevated PTH (21.76 pmol/l, 1.056.83). She was commenced on 2 μg alfacalcidol and calcichew, made a rapid recovery and was discharged on day 10. Six weeks post discharge, corrected calcium was 2.13 mmol/l with a marginally elevated phosphate, 1.96 mmol/l. PTH (3.98 pmol/l) and 25 hydroxy vitamin D (21 nmol/l) were now normal. 24 h urinary calcium excretion was 1.88 mmol/day (2.57.5) and 24 h urinary phosphate excretion was 86.0 mmol/day (1648). Lumbar spine BMD proved osteopenia (T and Z score −1.2). In view of evidence of end organ resistance to PTH, a diagnosis of pseudohypoparathyroidism type 1b (PHP 1b) was made.
PHP 1b is a genetic condition characterised by hypocalcaemia, hyperphosphataemia, hyperparathyroidism and lacking the phenotype of Albright Hereditary Osteodystrophy (PHP 1a). PHP 1b arises from GNAS imprinting defects in which methylation regions are lost resulting in a lack of expression of the G-protein subunit, Gsα, in the renal proximal tubules and renal PTH resistance. As synthetic PTH is unavailable in the UK, the EllsworthHoward test was not performed. Genetic analysis failed to detect the methylation defect typically observed in GNAS-1 although this does not exclude other genetic causes of PHP1b.
FH has several daughters with a history of hyperparathyroidism, hypocalcaemia and hyperphosphataemia with normal vitamin D levels. Despite not identifying a genetic defect in FH, the family history strengthens the argument for an inherited disorder.