Familial Hypocalcuric Hypercalcaemia (FHH) is an autosomal dominant condition associated with inactivating mutations of the human calcium sensing receptor (CaSR) gene (heterozygotes). Neonatal Severe Primary Hyperparathyroidism (NSHPT) affects infants who inherit two such inactivating copies (homozygotes). NSHPT is frequently fatal without parathyroidectomy (PTx).
Between 1984 and 2003 we have diagnosed and treated seven children (4M, 3F) with NSHPT. All children presented with a hypercalcaemic crisis with mean corrected calcium of 5.2 mmol (3.03-8.01) and elevated PTH of 175 (15-361). All children had features of severe bone demineralisation and a combination of vomiting, dehydration, poor feeding, and failure to thrive. One child had multiorgan failure, rib fractures with flail chest necessitating ventilation on ITU. None of the children had renal calcification or stones. Five children had CaSR gene mutations identified.
Initial treatment was re-hydration, low calcium diet, Frusemide, steroids, Calcitonin, and Bisphosphonates. Five children had surgery, 4 total and 1 subtotal PTx. The delay between diagnosis and surgery varied from 21 to 1063 days. Children who had total PTx had undetectable levels of PTH on discharge, tolerated treatment with alfacalcidol and calcium well, had no further re-admissions, caught up with development and show reversal of bone disease. One child had a 3.5 gland parathyroidectomy and remained mildly hypercalcaemic with high PTH levels. There were no post-operative complications.
Two children who had no surgery are now 18 and 12 years old and required medication to combat hypercalcaemia and multiple hospital admissions until late teens. Both patients biochemical profile now resembles FHH but they developed mild cognitive deficit and musculoskeletal problems.
Total PTx for NSHPT is safe, saves lives and reverses bone disease. Lack of clear indications for surgery results in long delays in treatment. Long term survival is possible without surgery but is associated with developmental and musculoskeletal problems.
22 - 24 Mar 2004
British Endocrine Societies