Persistent Neonatal Hypocalcemia as an Early Clue to TCIRG1-Related Infantile Osteopetrosis in an Infant of a Diabetic Mother: A Case Report.

Infantile malignant osteopetrosis is a rare autosomal recessive skeletal disorder caused by impaired osteoclast-mediated bone resorption, resulting in diffuse osteosclerosis, bone marrow failure, neurologic complications, and metabolic disturbances. Early diagnosis remains challenging, particularly when initial manifestations overlap with common neonatal conditions. Persistent neonatal hypocalcemia may be an early but underrecognized clue. We report a Saudi male infant with genetically confirmed TCIRG1-associated osteopetrosis who presented with persistent neonatal hypocalcemia and secondary hyperparathyroidism. Born at 36 weeks to a mother with insulin-dependent diabetes, he required neonatal intensive care for respiratory distress, hypoglycemia, and a right clavicular fracture following shoulder dystocia. Despite calcium supplementation, hypocalcemia persisted, prompting endocrinology evaluation. Laboratory investigations demonstrated recurrent hypocalcemia, elevated parathyroid hormone levels, and normal magnesium levels. Skeletal survey at three months of age revealed diffuse osteosclerosis with medullary cavity obliteration. Whole-exome sequencing identified a homozygous likely pathogenic TCIRG1 variant (c.1549G>A; p.Asp517Asn), confirming the diagnosis at three months of age. The disease subsequently progressed to pancytopenia, and the patient underwent hematopoietic stem cell transplantation at one year of age. At the most recent follow-up, 18 months post-transplant, the patient demonstrates adequate hematological recovery with stable blood counts and no significant neurological deficits. This case underscores the diagnostic challenge of infantile osteopetrosis when initial findings mimic common neonatal complications, particularly in infants of diabetic mothers. Persistent hypocalcemia with elevated parathyroid hormone, fractures, or unexpectedly increased skeletal density should prompt early skeletal evaluation and genetic testing to facilitate timely diagnosis and definitive treatment.