Background: A one-month girl was referred to our unit for hypocalcemia. She was the first child of healthy non-consanguineous parents. Her family history was unremarkable except a miscarriage in the mother and oligoasthenospermia in the father that justified a medically assisted reproduction. She was born eutrophic at term after a pregnancy marked by a moderate gestational diabetes. On day 3, a routine neonatal screening revealed a severe asymptomatic hypocalcemia (total calcium: 1.6 mmol/l). According to neonatal unit protocol, an oral treatment with calcium gluconate 200 mg/d and calcitriol 10 drops/d was started.
Laboratory investigations: On day 7 showed persistent hypocalcemia (total calcium: 1.89 mmol/l), phosphatemia at lower limit (1.4 mmol/l), normal alkaline phosphatase levels (223 UI/l), and low urinary calcium/creatinine ratio. Serum PTH levels were high (429 pg/ml), consistent with secondary hyperparathyroidism, and were associated with normal 25-hydroxyvitamin D (25OHD) level (30 ng/ml), and high 1,25-dihydroxyvitamin D (1,25(OH)2D) level (342 pg/ml).
Skeletal survey: Revealed the association of rickets with metaphyseal impairment and focused osteocondensation lesions on skull basis, limbs, and vertebrae, suggestive of osteopetrosis.
Genetic analysis: Found combined heterozygous mutation in the TCIRG1 gene, confirming a malignant neonatal osteopetrosis.
Evolution and management: Given the high levels of 1,25(OH)2D, calcitriol treatment was stopped and substituted by colecalciferol. On day 45, asthenia, pallor, and purpuric lesions were noted and CBC confirmed bicytopenia with anemia (9.2 g/dl) and thrombocytopenia (17 G/l). Moreover, because of eye tracking defect, investigations are underway to rule out an optic nerve compression. As TCIRG1 encodes a proton pump and cause osteoclast dysfunction, stem cell transplantation has been shown to be an effective treatment and was performed in our patient at 3 months of age.
Conclusion: Malignant osteopetrosis is a rare disease (estimated incidence of 1/200,000 live births) due to defective resorption of immature bone by osteoclasts. Paradoxal hypocalcemia can be the first sign of the disease as osteoclasts are unable to release calcium from bone. Without stem cell transplantation, the evolution can be fatal. Early diagnosis is required to perform stem cell transplant before neurosensorial impairment.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology