|Year : 2016 | Volume
| Issue : 3 | Page : 155-157
Vitamin D-dependent rickets type 2: Alopecia responding to 1,25 hydroxy Vitamin D
Prithi R Inamdar, Roopa M Bellad, Veena H Herekar
Department of Pediatrics, Jawaharlal Nehru Medical College, Belagavi, Karnataka, India
|Date of Web Publication||14-Sep-2016|
Prithi R Inamdar
A14/2 , Jawaharlal Nehru Medical College (JNMC) Quarters, Nehru Nagar, Belagavi - 590 010, Karnataka
Source of Support: None, Conflict of Interest: None
Vitamin D-dependent type two rickets (VDDRII) is a rare autosomal recessive disorder caused by mutation in the vitamin D receptor gene, leading to end-organ resistance to 1,25(OH) 2 vitamin D3. It presents with refractory rickets and growth retardation presenting in the first year of life. It is frequently associated with alopecia totalis. Due to target organ resistance, its response to vitamin D is poor. The recommended treatment is giving supraphysiological dose of 1,25(OH) 2 vitamin D3 and a high dose of oral or intravenous calcium. The response of alopecia to treatment is generally poor. We present a 3-year-old male child with VDDRII whose alopecia and rickets partially responded to 1,25(OH) 2 vitamin D3.
Keywords: Alopecia, end-organ resistance, vitamin D, 1,25(OH)2 vitamin D3
|How to cite this article:|
Inamdar PR, Bellad RM, Herekar VH. Vitamin D-dependent rickets type 2: Alopecia responding to 1,25 hydroxy Vitamin D. J Sci Soc 2016;43:155-7
| Introduction|| |
Vitamin D-dependent type two rickets (VDDRII) is a rare autosomal recessive disorder caused by mutation in the vitamin D receptor gene, leading to end-organ resistance to 1,25(OH) 2 vitamin D3. It presents with refractory rickets and growth retardation presenting in the first year of life.  It is frequently associated with alopecia totalis. Its biochemical parameters are hypocalcemia, hypophosphatemia, hyperparathyroidism, and elevated circulating levels of 1,25(OH) 2 vitaminD3. The significantly elevated serum levels of 1,25(OH) 2 vitamin D3 distinguishes this disorder from 1-α -hydroxylase deficiency, which is associated with low levels of 1,25(OH) 2 vitamin D3. Due to target organ resistance, its response to vitamin D is poor. The recommended treatment is giving supraphysiological dose of 1,25(OH) 2 vitamin D3 and high dose oral or intravenous calcium. The response of alopecia to treatment is generally poor although there has been one previous report of alopecia responding to 1,25(OH) 2 vitaminD3.  Till date, 50 unique mutations of vitamin D receptor gene have been noted. 
We present a 3-year-old male child with VDDRII whose alopecia and rickets partially responded to 1,25(OH) 2 vitamin D3.
| Case report|| |
We present a 4-year-old firstborn male child, born out of a nonconsanguineous marriage. He presented with progressive loss of hair since 3 months of age over the scalp and bilateral eyebrows. The mother also noticed progressive limb deformities in the form of inward curving of the forearms, bowing of legs, abnormal chest shape, and a large head. The child had gross motor developmental delay. He had achieved head-holding at 3 months, sitting without support at 1 year, and was not able to stand by himself. His other developmental domains were normal. The child also had a history of delayed dentition. He was born out of an uneventful pregnancy. There was no history suggestive of polyurea or polydipsia. At admission, the child's weight was 9.5 kg [<3 rd percentile the World Health Organization (WHO) weight for age], his length was 84 cm (<3 rd percentile WHO weight for age), and he had a normal head circumference of 50 cm. He had evidence of rickets in the form of wide open anterior fontanel, frontoparietal bossing, ricketic rosary, Harrison's sulcus, wrist widening, protuberant abdomen, double malleolie, and bowed legs [Figure 1]. There was no evidence of other vitamin or mineral deficiencies.
|Figure 1: Child presented with aloplecia, bow legs, double malliolie and ricketic rossary|
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Investigations revealed a normal hemogram. His renal function tests (urea - 21 mg/dL, serum creatinine - 0.5 mg/dL), sodium (137 mEq/L), potassium (3.8 mEq/L), and venous bicarbonate l (18 mmol/L) were in the normal range, ruling out the renal etiology of rickets. His serum calcium was low (6.9 mg/dL) and the x-ray of his wrist was suggestive of rickets, which was further confirmed by raised parathormone levels of 872.1. His 25(OH) 2 vitamin D3 levels indicated insufficiency (17.3) and 1,25(OH) 2 vitamin D3 levels were raised, suggestive of end-organ insensitivity. Ultrasound of the abdomen was normal without any nephrocalcinosis.
The patient was given intravenous calcium gluconate for 3 days and was started on 1, 25-OH vitamin D at dose of 2 mcg/kg daily and oral calcium at 1,000 g/day. At 1-month follow-up, the patient showed an improvement in motor functions. He could stand with support. His scalp showed a few areas of hair growth where there was alopecia before treatment.
| Discussion|| |
When there is a high prevalence of nutritional rickets, other etiologies of rickets are often not thought of. This results in the delayed initiation of treatment, resulting in severe growth retardation and deformities. Estimation of vitamin D levels are costly and high doses of vitamin D is routinely given without confirming diagnosis. Such unwarranted treatment may lead to nephrocalcinosis, especially in renal tubular acidosis. Red flag signs suggesting nonnutritional etiology are early onset of rickets, severe deformity, deformities localized to lower limbs, associated failure to thrive, acidotic breathing, and the presence of dental abscesses, cataracts, or alopecia.
Our patient had alopecia with severe deformities, aiding the diagnosis.
VDDRII is an extremely rare disorder caused by target organ resistance to 1,25(OH)2 vitamin D, the biologically active form of vitamin D. There are a few isolated case reports from India earlier but the exact prevalence of the disease is not yet known. , It is diagnosed through the finding of normal or elevated circulating levels of 1,25(OH)2 vitamin D, which differentiate it from vitamin D-dependent rickets type I (VDDR I). The latter is caused by defective 1-α-hydroxylation of 25(OH) vitamin D in the kidneys, resulting in low serum levels of 1,25(OH) vitamin D3.  The most common defect is undetectable binding of 1,25(OH)2 vitamin D to the receptor either because of an absent VDR or a defective steroid-binding domain of the vitamin D receptor (VDR).  Patients with VDDR 2 are early-onset rickets, hypocalcemia, and associated total body alopecia.  The alopecia may be present at birth or within the first few months of life and progresses to aloplecia totalis by childhood. Aloplecia is generally not responsive to treatment.  In a study by Sadomoto et al., the cells from a patient with VDDR II with alopecia did not respond to the hormone, suggesting a lack of the specific receptors in the cells unresponsive to 1,25(OH) 2 vitamin D3 treatment.  The development of alopecia is felt by some investigators to be associated with a more profound 1,25(OH) 2 vitamin D3 resistance. Marx et al. reviewed and analyzed the relationship between alopecia and resistance to 1,25(OH) 2 vitamin D3 in 22 cases from 30 kindreds in whom they noticed that alopecia was associated with the severest grades of resistance to 1,25(OH) 2 vitamin D3.  There is one previous case report of alopecia in VDDR II responding to 1,25(OH) 2 vitamin D3.  We also found a similar improvement in alopecia. There is a report of two patients by Takeda et al., with presentation of only alopecia in the absence of rachitic changes, which might be explained by differences in sensitivity to 1,25(OH)2D3 of bone formation and hair growth. 
The use of intravenous high-dose calcium infusions followed by a high dose of oral calcium is an effective method of treatment of VDDRII. The treatment is more effective if started early in the course of the disease and leads to early healing and better growth with prevention of bone deformities. Early treatment may also lead to improvement in alopecia, the mechanism for which needs to be elucidated. 
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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