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Saudi Journal of Kidney Diseases and Transplantation
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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

Department of Nephrology, Mediciti Hospitals, Hyderabad, Andhra Pradesh, India

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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.

Keywords: Vitamin D dependent rickets type II (VDDR II), Calcidiol, Calcitriol

How to cite this article:
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;19:796-8

How to cite this URL:
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 2022 Dec 7];19:796-8. Available from: https://www.sjkdt.org/text.asp?2008/19/5/796/42463

   Introduction Top

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.

   Case Report Top

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].

   Discussion Top

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 [1] 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. [2],[3],[4]

Eil et al [5] 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. [6] The prenatal diagnosis of VDDR-II by analysis of amniotic fluid cells and fetal tissue is indicated in high risk families. [7] These patients are prone for infections because of immune dysfunction and impaired neutrophilic chemotaxis. [8]

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. [9] The­rapy with high dose vitamin D analogues is found to be effective as in our case. Takeda E [10] 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 [11] or in combination with intravenous cal­cium [12] are also reported to be effective treat­ment options.

   References Top

1.Brooks MR, Bell NH, Love L, et al. Vitamin­D-dependent rickets type II: Resistance of target organs to 1,25-dihydroxyvitamin D. N Engl J Med 1978;298(18):996-9.  Back to cited text no. 1    
2.Liberman UA, Halabe A, Samuel R, et al. End­organ resistance to 1,25-dihydroxychole­calciferol. Lancet 1980;(8167):504-7.  Back to cited text no. 2    
3.Marx SJ, Spiegel AM, Brown EM, et al. A familial syndrome of decrease in sensitivity to 1,25-dihydroxyvitamin D. J Clin Endocr Metab 1978;47(6):1303-10.  Back to cited text no. 3    
4.Rosen JF, Fleishman AR, Finberg L, Hamstra A, DeLuca HF. Rickets with alopecia: an inborn error of vitamin D metabolism. J Pediatr 1979;94(5):729-35.  Back to cited text no. 4    
5.Eil C, Liberman UA, Rosen JF, Marx SJ. A cellular defect in hereditary vitamin-D­dependent rickets type II: Defective nuclear uptake of 1,25-dihydroxyvitamin D in cultured skin fibroblasts. N Engl J Med 1981;304 (26):1588-91.  Back to cited text no. 5    
6.Takeda E, Kuroda Y, Saijo T, et al. Rapid diagnosis of vitamin D-dependent rickets type II by use of phytohemagglutinin-stimulated lymphocytes. Clin Chim Acta 1986;155(3): 245-50.  Back to cited text no. 6    
7.Weisman Y, Jaccard N, Legum C, et al. Prenatal diagnosis of vitamin D-dependent rickets, type II: Response to 1,25-dihydroxy­vitamin D in amniotic fluid cells and fetal tissues. J Clin Endocrinol Metab 1990;71(4): 937-43.  Back to cited text no. 7    
8.Walka MM, Daumling S, Hadorn HB, Kruse K, Belohradsky BH. Vitamin D dependent rickets type II with myelofibrosis and immune dysfunction. Eur J Pediatr 1991;150(9):665-8.  Back to cited text no. 8    
9.Malloy PJ, Eccleshall TR, Gross C, Van Maldergem L, Bouillon R, Feldman D. Heredi­tary vitamin D resistant rickets caused by a novel mutation in the vitamin D receptor that results in decreased affinity for hormone and cellular hyporesponsiveness. J Clin Invest 1997;99(2):297-304.  Back to cited text no. 9    
10.Takeda E, Yokota I, Kawakami I, Hashimoto T, Kuroda Y, Arase S. Two siblings with vitamin-D-dependent rickets type II: No recu­rrence of rickets for 14 years after cessation of therapy. Eur J Pediatr 1989;149(1):54-7.  Back to cited text no. 10    
11.Wong GW, Leung SS, Law WY, Cheung NK, Oppenheimer SJ. Oral calcium treatment in vitamin D-dependent rickets type II. J Paediatr Child Health 1994;30(5):444-6.  Back to cited text no. 11    
12.Al-Aqeel A, Ozand P, Sobki S, Sewairi W, Marx S. The combined use of intravenous and oral calcium for the treatment of vitamin D dependent rickets type II (VDDRII). Clin Endocrinol (Oxf) 1993;39(2):229-37.  Back to cited text no. 12    

Correspondence Address:
Anuradha S Raman
Department of Nephrology, Mediciti Hospitals, 5-9-22, Secretariat Road, Hyderabad, Andhra Pradesh, 500063
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Source of Support: None, Conflict of Interest: None

PMID: 18711299

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