Endocrine Abstracts

Introduction: Autosomal Dominant Hypocalcemia (ADH) presents with low calcium and high phosphorus levels due to hypoparathyroidism. It is categorized into type 1, resulting from gain-of-function mutations in the calcium-sensing receptor (CASR), and type 2, caused by activating mutations in GNA11, a key mediator in CASR signaling. Our contribution involves reporting a rare case of pediatric ADH 2.

Case presentation: We present the case of a 9-year-old boy who first addressed the Department of Endocrinology Iasi to investigate short stature and low Body Mass Index (BMI) (Height at -2.89SD and BMI at - 4.46SD) and persistently low levels of calcium and PTH. In his medical background, we highlight the diagnosis of gut dysbiosis at the age of 6. It is important to mention that the older brother and the father experience chronic hypocalcemia, the father suffering from clinical manifestations of hypocalcemia. Hormonal and biochemical assessment eliminated the possibility of adrenal and thyroid dysfunction. Regarding somatotropic axis, the baseline values of GH and IGF1 were low with no adequate stimulation of GH when stimulated with arginine. Low IGF1 may be in the context of malnutrition, but this does not explain GH deficiency. HrGH treatment was initiated with height improving to -1.93SD in 18 months. Because of the alteration in phosphate-calcium balance, genetic testing was done. It was identified a heterozygous mutation of the GNA11 gene, c.178c>t (p.arg60cys), responsible for the development of ADH2. Treatment with calcitriol was underwent for 18 months. Calciuria begun to rise, and together with the elevated phosphates and the absence of symptoms lead to the therapeutic decision to stop calcitriol considering the risk of renal lithiasis and calcification of basal nuclei.

Discussion: The protein produced of GNA11 gene is the alfa subunit of G11 protein that functions alongside CASR in calcium regulation. The activating mutation of GNA11 is accountable of developing ADH2. Data from literature show that ADH2 is associated with a milder phenotype in terms of hypocalcemia and it is rarely associated with hypomagnesemia or hypercalciuria, possibly because CASR couples with proteins other than G11 in the kidney. ADH2 patients present more often short stature, implying that GNA11 plays a role in skeletal growth, and calcifications of the basal ganglia. The treatment is not recommended in asymptomatic patients.

Conclusion: Although genetic disorders are not a common cause of hypoparathyroidism, accurate diagnosis of the underlying genetic etiology is essential, affecting treatment goals, comorbidity screening, and family planning.