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Vitamin D dependent rickets type II with myelofibrosis and immune dysfunction
M M Walka1, S Däumling, H B Hadorn
1Dr. von Haunersches Kinderspital, Universität München, Federal Republic of Germany.
Insights
This study details a patient with vitamin D-dependent rickets type II, highlighting severe skeletal and hematological issues. Treatment with calcium infusions improved symptoms, suggesting a link between myelofibrosis and hyperparathyroidism in this rare genetic disorder.
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.
Abstract:
We present a new patient with vitamin D dependent rickets type II. A 20-month-old Arabian boy whose parents are first cousins showed florid rickets, myelofibrosis and recurrent septicaemia. In addition to absent specific binding for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). 25-Hydroxyvitamin D3-24-hydroxylase activity could not be induced in cultured fibroblasts. The patient did not respond to 99 micrograms 1,25(OH)2D3 per day, but skeletal and haematological abnormalities improved with daily infusion of 100 mg/kg calcium, as serum parathyroid hormone levels fell to normal values. At the age of 7 years, he died from pneumonia. The improvement of haematological abnormalities with calcium infusions but not with 1.25(OH)2D3 suggests a pathogenetic relationship of myelofibrosis and hyperparathyroidism. Having anti-lipid A IgM antibody titres up to 1:10.000 after Gram negative septicaemias, the patient never produced corresponding IgG antibodies. His neutrophil chemotaxis was persistently reduced to 57% +/- 3% of age-matched controls (P less than 0.028). The patient showed two pathological immune functions considered to contribute to the well-known susceptibility to infection in rickets.