Endocrine Abstracts

We present a diagnostically challenging case of a 22-year old female with short stature and recurrent admissions with severe hypokalaemia, hypocalcaemia and hypomagnesaemia since infancy.

Case: Our patient was born at 38 weeks gestation following a pregnancy complicated by intrauterine growth restriction since 28 weeks. She had low birthweight of 2.4 kg and significantly shorter length and lower head circumference than expected. Mild dysmorphic features of frontal bossing, microphthalmia and mid-facial hypoplasia were evident. Both parents were unrelated, healthy Caucasians of average height.

Her childhood was complicated by growth failure despite normal stimulated GH and IGF-1 levels. Baseline IGF-1 was low at 24 ng/ml. Skeletal surveys showed gracile bones, oligodontia with hypoplastic mandibular condyles and a j-shaped sella. MRI pituitary was normal. She had three trials of GH therapy in childhood which complicated high hypermetropia with macular oedema and visual worsening.

Since infancy, the patient has suffered recurrent and resistant hypocalcaemia, hypomagnesaemia and hypokalaemia requiring frequent hospitalisation. Biochemistry confirms persistent hypoparathyroidism and renal magnesium and potassium loss. Calcium: creatinine ratio, renin and aldosterone were normal. She is treated with alfacalcidol 1 microgram daily and varying doses of calcium carbonate, magnesium and potassium replacement.

An encompassing diagnosis was difficult to achieve, until at the age of 21 years, genomic sequencing confirmed a de-novo heterozygous c.1706G>A transition in the FAM111A gene diagnostic of Kenny-Caffey Syndrome 2.

Kenny- Caffey Syndrome 2 (KCS2): KCS2 is extremely rare with less than 60 cases reported in the English literature. The function of the associated FAM111A gene product isn’t fully known but seems to have a fundamental role in bone growth and parathyroid hormone regulation. There is consensus that hypoparathyroidism drives hypocalcaemia but this does not explain the recurrent hypomagnesaemia and hypokalaemia seen in our patient. Further research of the FAM111A gene is needed to better understand this disease presentation.