Severe Parathyroid Hormone (PTH)-Independent Hypercalcemia Revealing Precursor B-cell Acute Lymphoblastic Leukemia in...

Hypercalcemia is an uncommon metabolic disorder in children and a rare complication of pediatric malignancies. Acute lymphoblastic leukemia (ALL) presenting with severe hypercalcemia and osteolytic bone lesions is rare in pediatric patients. We report the case of a previously healthy two-year-old male who presented with a one-month history of progressive lower limb weakness, fatigue, and altered responsiveness. Guillain-Barré syndrome was initially suspected but became less likely following normal electromyography (EMG) and spinal MRI findings. Initial investigations revealed severe hypercalcemia (212 mg/L; 5.3 mmol/L), hypophosphatemia, hyperuricemia, elevated lactate dehydrogenase (LDH) levels, and mildly impaired renal function. A shortened QT interval on ECG prompted pediatric ICU (PICU) admission, where the patient received hyperhydration and bisphosphonates, resulting in partial biochemical improvement. Endocrine evaluation showed suppressed parathyroid hormone (PTH) (4 pg/mL), normal 25-OH vitamin D (23 ng/mL), and normal thyroid function tests, supporting a PTH-independent etiology of hypercalcemia. Persistent hypercalcemia combined with microcytic anemia, elevated uric acid, and LDH levels raised suspicion of an underlying malignancy. Skeletal radiographs demonstrated multiple bilateral osteolytic lesions involving the femurs, tibias, and fibulas. Bone marrow aspiration revealed 27% blasts, and flow cytometry demonstrated a CD34-positive and CD45-dim blast population consistent with precursor B-cell ALL. Serum calcium normalized progressively before chemotherapy initiation after initial aggressive hyperhydration followed by repeated zoledronic acid administration, and the patient was subsequently transferred to the oncology department for treatment according to the ALL IC-BFM 2009 protocol. Clinical and neurological improvement followed progressively. This report highlights the diagnostic challenge of malignant hypercalcemia in children, particularly in the absence of circulating blasts or organomegaly. Severe PTH-independent hypercalcemia associated with osteolytic lesions should raise suspicion for ALL, even in very young children. Skeletal radiography provided the pivotal diagnostic clue after a one-month delay in diagnosis, ultimately leading to bone marrow evaluation and diagnosis.