Vitamin D-dependency rickets in institutionalized, mentally retarded children on long term anticonvulsant therapy. II. The response to 25-hydroxycholecalciferol and to vitamin D2.

Abstract

Extract: Eight mentally retarded children with vitamin D-dependency rickets associated with long term anticonvulsant medication are reported. All had been institutionalized for most of their lives, and had marked cerebral palsy. Their ages ranged from 3.5–9.5 years. All suffered from a chronic convulsive disorder and had been treated for 3 years or more with various combinations of Dilantin, Mysoline, and phenobarbital. They had no alterations in hepatic, renal, or intestinal functions.Rickets ensued in these children despite an intake of conventional doses of oral vitamin D2 taken prophylactically throughout life. Three patients failed to respond to treatment with doses of up to 6,000 IU/24 hr given orally. In one instance, 2,000 IU vitamin D2 was given for 7 months, with no response. However, in three patients, healing was induced with higher doses of vitamin D2; one healed with 15,000 IU vitamin D2 daily for 10 weeks, and two responded to a single oral dose of vitamin D2 of 600,000 IU. Another patient did not improve after one single oral dose of 0.5 mg dihydrotachysterol. In contrast, 50 IU 25-hydroxycholecalciferol daily by mouth induced rapid healing in five patients. There was a rapid rise in serum PC4 levels within the 1st week of this therapy, with radiographic healing apparent after 1 month. However, the serum calcium levels remained low throughout 4–5 months of therapy. When the dose of 25-hydroxycholecalciferol (25-OH-D3) was increased to 100 IU/24 hr, the hypocalcemia was corrected. In some of these patients there was an amelioration of convulsions after rickets was treated. It is suggested that children who reside in institutional care centers, who are on long term anticonvulsant drugs, be given vitamin D supplements greater than the usual prophylactic dose, and also (perhaps more appropriately) that serial serum calcium, phosphate, and alkaline phosphatase estimations be performed regularly in such children as well as long bone radiographs when indicated.Speculation: The rapid response to small dosages of 25-OH-D3 is evidence suggestive that the mechanism for rickets induction in patients on long term anticonvulsant therapy is one of interference of vitamin D metabolism at the stage of hepatic conversion from cholecalciferol to its 25-hydroxy metabolite. Other factors such as levels of sunlight exposure, relative inactivity, and chronic recurrent infections, may also play a role in the development of rickets in these patients.