Introduction: Osteopetrosis (OP) is a rare genetic disorder that is characterized by abnormal osteoclast function resulting in dense bones and marrow failure. The only definitive cure for OP is stem cell transplantation (SCT). Hypercalcemia is a well described complication in children with OP undergoing SCT. This study describes the calcium profile and treatment modalities used to maintain normocalcemia in children with OP undergoing SCT.
Aim: To study the calcium profile of all patients with OP who underwent SCT from 2012 till date at our institution.
Results: Five children (all males) with OP underwent SCT at a median age of 10 months (9-22months). Baseline median serum calcium was 8.3 mg/dl (7.3-8.9mg/dl). Source of graft was peripheral blood in 1 child and bone marrow in 4 children. Hypercalcemia (serum calcium >11mg/dl) developed in 2/5 at a mean of +12 days post SCT.Of the two, one child aged 12 months with negative genetic studies developed hypercalcemia for 8 days (peak S.calcium 15.62 mg/dl). The second child aged 22 months with positive TNFRSF11A gene mutation has ongoing hypercalcemia at +270days post SCT (peak S.calcium 16.8 mg/dl). Hypercalcemia was managed with forced diuresis, corticosteroids, calcitonin and Pamidronate with the second child receiving Cinacalcet in addition. A third child aged 9 months maintained normocalcemia with forced diuresis for an increasing trend of serum calcium level (from7.3 to 10.7 mg/dl). Of the three children who maintained normal calcium level post SCT, 2 were positive for TCIRG1 and CLCN7 mutation respectively, and 1 had negative genetic studies. 1 of these 3 children expired of sepsis and multiorgain failure on day +33 post SCT.
Discussion: Despite a low/normal baseline serum calcium level and lower age, hypercalcemia occurred in 40% children with OP undergoing SCT in our centre as compared to other studies(1). The duration of hypercalcemia was variable. The efficacy of Cinacalcet and long term effects of bisphosphonate therapy in this setting remains unclear.
Conclusion: Hypercalcemia is an expected complication in children with Osteopetrosis undergoing SCT. Both the absolute serum calcium level and its rising trend must be monitored closely in these children. The onset, duration and severity of hypercalcemia is variable and may require multiple pharmacological agents to maintain normocalcemia. Further studies are needed to assess predictors for hypercalcemia and establish genotype-phenotype correlation to understand risk factors for life-threatening hypercalcemia.
References: 1.Gerritsen et al.Bone marrow transplantion for autosomal recessive osteopetrosis J Pediatr.1994Dec;125:896902
19 - 21 Sep 2019
European Society for Paediatric Endocrinology