Background: Thymus transplantation is undertaken for conditions associated with severe immunodeficiency. These comprise a number of genetic and syndromic associations including 22q deletion syndrome, CHARGE association, diabetic embryopathy, and other rarer conditions. These conditions may also be associated with hypoparathyroidism and patients are therefore at risk of severe hypocalcaemia. There are no published guidelines for calcium replacement in these patients during the pre and post transplant period.
Case series: Twenty-nine patients (age 2 months-2 years, 20 male) from the UK and 13 European centres underwent thymus transplantation between 2009 and 2018. The underlying diagnoses included 22q11.2 (n=17, 1 with a phenotype only of 22q11.2), CHARGE association (n=8), diabetic embryopathy (n=2), FOXN1 mutation (n=1), and TBX1 mutation (n=1). 93% had hypoparathyroidism prior to transplant, treated with enteral calcium supplementation on admission. 79% had hypocalcaemia (defined in this cohort as corrected calcium (cCa)<2.0 mmol/l) during admission. The mean nadir in the entire cohort was cCa=1.7 mmol/l (1.22.4 mmol/l). This occurred from 45 days pre-transplant to 35 days post-transplant (mean=day+1 post-transplant). 55% of patients required intravenous calcium during admission, and 35% required continuous calcium infusions. A diagnosis of 22q11.2 was associated with a slight increase in likelihood of requiring intravenous calcium (Likelihood Ratio =1.4, 63% of patients with 22q11.2 compared to 46% with alternate diagnosis). The mean duration of intravenous treatment was 4.7 days (139 days) and calcium requirements varied from 0.7 to 2.4 mmol/kg per day (mean=0.7 mmol/kg per day.) Associated complications included prolonged length of stay [median=28 days (11255)], admission to intensive care (24%), hypocalcaemic seizures (14%), nephrocalcinosis (20% of those who underwent sonographic evaluation), infection (68%), mortality (10%).
Conclusion: This case series highlights the variability and unpredictability of severe hypocalcaemia in patients undergoing thymus transplantation. This vulnerable cohort is at significant risk of hypocalcaemia due to conditioning for transplant (including anti-thymocyte globulin (ATG)), hypoparathyroidism, the surgical procedure itself and post-operative reduced enteral absorption. Our practice has evolved over the past decade to include commencement of prophylactic intravenous calcium infusions in patients with borderline hypocalcaemia at the start of conditioning. Further studies are warranted to evaluate whether early pre-operative intravenous calcium therapy reduces post-operative complications related to hypocalcaemia and length of hospital stay. The lack of standardised evidence-based guidelines for the management of these patients has important implications for morbidity, mortality and healthcare cost.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology