Identification and Management of Familial Hypocalciuric Hypercalcemia Type 3 in a District General Hospital
J Chui Hom Lap1, S Zac-Varghese2, 1UCL medical student, 2Lister Hospital - East and North Hertfordshire NHS Trust
We present a 29-year-old Caucasian lady, referred to Endocrinology with an asymptomatic, elevated adjusted calcium of 2.84 mmol/L.
Of interest, her mother had previously been investigated for apparent recurrent hyperparathyroidism and diagnosed with FHH type 3. Her mother had previously been discharged from the endocrine service.
Initial biochemistry, revealed a low urinary calcium creatinine clearance ratio of 0.002, an elevated PTH 10.92 pmol/ L, phosphate 0.97 mmol/L and ALP 81 U/L. Genetic testing confirmed a heterozygous AP2S1 mutation consistent with FHH
Familial hypocalciuric hypercalcaemia (FHH) is a rare, genetically heterogenous condition, characterised by raised serum calcium concentrations and low levels of urinary calcium excretion. The majority of FHH cases can be confirmed via genetic testing for a calcium sensing receptor (CASR) gene mutation. Loss of function mutations lead to FHH type 1 which is a benign condition. FHH3 is a much rarer genetic variant with normal CASR genes, accounting for 5-8 % of total FHH cases.
It is important to consider FHH in patients with hypercalcaemia and very low urinary calcium creatinine clearance ratio. However, differentiating FHH from primary hyperparathyroidism is in some cases difficult due to the similarity in clinical and biochemical features. Genetic confirmation of FHH may be required to avoid unnecessary surgical intervention. Specific genetic testing for CASR mutations will lead to a missed diagnosis of FHH3. Gene panel testing, including testing for AP2S1, is a more sensitive method to identify underlying genetic disorders.
People with FHH type 1 can be safely discharged from the endocrine service and need no further investigation or monitoring. FHH type 3, however, is not considered a benign condition and is associated with severe osteoporosis and some cognitive deficit. The patient and her mother will now be monitored life-long for symptoms of hypercalcaemia alongside investigation for osteoporosis including vitamin D and bone mineral density levels.