Year : 2008 | Volume
: 19 | Issue : 5 | Page : 796--798
Vitamin D Dependent Rickets Type II: Late Onset of Disease and Response to High Doses of Vitamin D
Sachin S Soni, Gopal Kishan Adikey, Anuradha S Raman
Department of Nephrology, Mediciti Hospitals, Hyderabad, Andhra Pradesh, India
Anuradha S Raman
Department of Nephrology, Mediciti Hospitals, 5-9-22, Secretariat Road, Hyderabad, Andhra Pradesh, 500063
Vitamin D dependent rickets Type II is a rare autosomal recessive disorder. The disorder is characterized by end organ hyporesponsiveness to vitamin D. Common presentation of the disorder is total body alopecia and onset of rickets during the second half of the first year of life. Patients may display progressive rachitic bone changes, hypocalcemia and secondary hyperparathyroidism. It is differentiated from vitamin D dependent rickets type I by virtue of response to physiological doses of exogenous vitamin D in the later. Target organ hyporesponsiveness can be overcome by higher doses of vitamin D or its analogues. We report a case of vitamin D dependent rickets type II with onset of rickets at the age of thirteen years without alopecia progressing to marked disability by twenty three years of age. She responded to massive doses of vitamin D with significant clinical improvement after six months of therapy.
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Soni SS, Adikey GK, Raman AS. Vitamin D Dependent Rickets Type II: Late Onset of Disease and Response to High Doses of Vitamin D.Saudi J Kidney Dis Transpl 2008;19:796-798
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Soni SS, Adikey GK, Raman AS. Vitamin D Dependent Rickets Type II: Late Onset of Disease and Response to High Doses of Vitamin D. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2019 Nov 21 ];19:796-798
Available from: http://www.sjkdt.org/text.asp?2008/19/5/796/42463
Vitamin D dependent rickets (VDDR) type II results from a recessively inherited abnormality in the calcitriol receptor, causing an end-organ resistance to the vitamin. The clinical profile consists of early onset rickets with severe hypocalcemia. Depending on presence or absence of alopecia it is further classified as VDDR type IIA or IIB, respectively. Serum levels of 1,25(OH)2 vitamin D3 are typically elevated. Treatment consists of high dose vitamin D or its analogues and/or calcium supplement.
We report a case of VDDR type IIB responding to high dose vitamin D therapy.
A 24–year-old woman, presented with a history of limping for two years. She was started on calcium supplements; however, she progressively developed marked weakness, gait abnormality, easy fatigability, and cramps. At the age of 12 years, the patient underwent surgery for genu valgum deformity of both knees. She was a product of non consanguineous marriage and second in the order of five siblings. In addition, she was short compared to her peers and siblings.
Clinical examination revealed stable vitals, height of 142 cm and disparity in limb lengths; right lower limb was longer by 0.8 cm. Features of severe hypocalcemia (Chvostek's sign and carpopedal spasms) were positive. Alopecia or features of nutritional deficiency were not observed.
Investigations revealed severe hypocalcemia (Serum calcium: 6.3 mg/dL) and hypophosphataemia: 2.1 mg/dL), as well as markedly raised alkaline phosphatase and parathormone levels. Results of liver function tests, renal function tests, hemogram, serum electrolytes, arterial blood gas, and serum magnesium were within normal limits. Skeletal survey did not reveal features of rickets or osteomalacia. Evaluation for renal tubular acidosis and hypophosphatemic rickets were negative. Levels of Vitamin D metabolites disclosed normal 25–hydroxy vitamin D, however, markedly increased 1,25 dihydroxy vitamin D. In our case, the onset of disease at 12 years of age the absence of response to routine doses of calcium supplements, and the characteristic laboratory abnormalities were compatible with the diagnosis of Vitamin D dependent rickets type IIB.
The patient was initiated on high dose vitamin D therapy (Inj. Vitamin D- 600,000 units each week for a month followed by the same dose every two weeks) and calcium supplements. She responded to this regimen with rapid symptomatic improvement and normalization of laboratory parameters. Her bone densitometry also illustrated significant improvement, [Figure 1].
Vitamin D dependent rickets type II is alternatively known as pseudovitamin D-deficiency type II, hypocalcemic vitamin D-resistant rickets, and rickets-alopecia syndrome. The disorder is characterized by end organ resistance to physiological doses of 1,25 dihydroxy cholecalciferol. The basic defect involves the unresponsiveness of vitamin D receptor (VDR) to 1,25dihydroxyvitamin D. Brooks et al  in 1978 first reported a 22–year-old African American woman with hypocalcemia, secondary hyperparathyroidism, osteomalacia, and osteitis fibrosa cystica in association with normal serum 25–hydroxyvitamin D and markedly increased serum 1,25–dihydroxyvitamin D. They labeled this syndrome as VDDR type II. Many publications followed reporting similar clinical observations of early onset vitamin D unresponsive rickets and severe hypocalcemia with or without alopecia. ,,
Eil et al  demonstrated defective nuclear uptake of 1,25–dihydroxyvitamin D in cultured fibroblasts from these patients. Laboratory clue to diagnosis of VDDR II is high level of 1,25–dihydroxyvitamin D in a patient with hypocalcemia and non-azotemic rickets, as observed in our case. Rapid molecular diagnosis is also possible by testing the effects of 1,25–(OH)2D3 on thymidine incorporation into PHA-stimulated lymphocytes.  The prenatal diagnosis of VDDR-II by analysis of amniotic fluid cells and fetal tissue is indicated in high risk families.  These patients are prone for infections because of immune dysfunction and impaired neutrophilic chemotaxis. 
VDDR II is an autosomal recessive disorder caused by a defect in the vitamin D receptor gene located on chromosome 12q12–q14. Thus far, 13 mutations have been identified.  Therapy with high dose vitamin D analogues is found to be effective as in our case. Takeda E  reported a sibling cured by treatment with 50,000 IU of vitamin D2 daily for 2 years without any recurrence for 14 years after cessation of therapy. High dose oral calcium alone  or in combination with intravenous calcium  are also reported to be effective treatment options.
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