Vitamin D dependent rickets type II with myelofibrosis and immune dysfunction

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 μg 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 antilipid 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<0.028). The patient showed two pathological immune functions considered to contribute to the well-known susceptibility to infection in rickets.