Vitamin D dependent rickets type II with myelofibrosis and immune dysfunction

Area of Science:

• Pediatrics
• Endocrinology
• Genetics

Background:

• Vitamin D-dependent rickets type II (VDDR-II) is a rare genetic disorder characterized by resistance to 1,25-dihydroxyvitamin D3.
• VDDR-II results from mutations in the vitamin D receptor (VDR) gene, leading to impaired vitamin D signaling.
• This case highlights the complex clinical manifestations and management challenges of VDDR-II.

Observation:

• A 20-month-old boy with consanguineous parents presented with severe rickets, myelofibrosis, and recurrent infections.
• The patient exhibited absent specific binding for 1,25-dihydroxyvitamin D3 and failed to induce 25-hydroxyvitamin D3-24-hydroxylase activity.
• Despite resistance to 1,25-dihydroxyvitamin D3, skeletal and hematological abnormalities improved with calcium infusions.

Findings:

• Treatment with high-dose calcium infusions normalized serum parathyroid hormone levels and improved skeletal and hematological abnormalities.
• The patient demonstrated impaired antibody production (lack of IgG) after Gram-negative septicemias and reduced neutrophil chemotaxis.
• These findings suggest a potential pathogenetic link between myelofibrosis, hyperparathyroidism, and immune dysfunction in VDDR-II.

Implications:

• This case underscores the critical role of calcium and parathyroid hormone regulation in managing severe VDDR-II.
• The observed immune deficits contribute to the increased susceptibility to infections in patients with rickets.
• Further research into VDR function and its impact on hematopoiesis and immunity is warranted.