CASE REPORT - MISCELLANEOUS
|Year : 2019 | Volume
| Issue : 4 | Page : 130-133
Familial Vitamin D-dependent rickets Type 2A: A report of two cases with alopecia and oral manifestations
Department of Oral and Maxillofacial Pathology, Mamata Dental College and Hospital, Khammam, Telangana, India
|Date of Submission||13-Dec-2018|
|Date of Acceptance||16-Jan-2019|
|Date of Web Publication||22-Feb-2019|
Department of Oral and Maxillofacial Pathology, Mamata Dental College and Hospital, Giriprasad Nagar, Khammam - 507 002, Telangana
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Rickets is a metabolic bone disease that develops as a result of inadequate mineralization of growing bone due to disruption of calcium, phosphorus and/or Vitamin D metabolism. In addition, several rare genetic causes of rickets have also been described, which can be divided into two groups. The first group consists of genetic disorders of Vitamin D biosynthesis and action, such as Vitamin D-dependent rickets Type 1A, Type 1B, Type 2A (VDDR2A) and Type 2B. The second group involves genetic disorders of excessive renal phosphate loss (hereditary hypophosphatemic rickets). VDDR2A is a rare autosomal recessive disorder caused by mutation in the Vitamin D receptor gene, leading to end-organ resistance to 1,25(OH)2Vitamin D3. It clinically represents growth retardation presenting in the 1st year of life and frequently associated with alopecia totalis, which differentiates it from VDDR Type 1. Due to target organ resistance, its response to Vitamin D is poor. We report two cases of familial VDDR2A, with alopecia and oral manifestations.
Keywords: Alopecia, calcium, rickets, Vitamin D
|How to cite this article:|
Thakur M. Familial Vitamin D-dependent rickets Type 2A: A report of two cases with alopecia and oral manifestations. J Oral Maxillofac Pathol 2019;23, Suppl S1:130-3
|How to cite this URL:|
Thakur M. Familial Vitamin D-dependent rickets Type 2A: A report of two cases with alopecia and oral manifestations. J Oral Maxillofac Pathol [serial online] 2019 [cited 2020 Aug 6];23, Suppl S1:130-3. Available from: http://www.jomfp.in/text.asp?2019/23/4/130/252731
| Introduction|| |
Rickets is a metabolic bone disorder that develops as a result of decreased mineralization of the growth plate in the growing infant, child and adults due to defect in metabolism or functions of calcium or phosphate and/or deficiency of Vitamin D or decreased activity of alkaline phosphatase., Rickets is classified into various types, but broadly classified based on common etiological factors into two types as calciopenic (defect in metabolism or functions of calcium/deficiency of Vitamin D) or phosphopenic (renal phosphate wasting).,
In addition, genetic causes of rickets (hereditary rickets) are rare, accounting for about 13% of total rickets. They are classified into two groups. The first group consists of genetic disorders of Vitamin D biosynthesis and action, such as Vitamin D-dependent rickets Type 1A (VDDR1A), Type 1B (VDDR1B), Type 2A (VDDR2A) and Type 2B (VDDR2B). Inactivating homozygous or compound heterozygous mutations of VDR (MIM#601769), the gene encoding the Vitamin D receptor called Vitamin D-resistant rickets or VDDR Type 2A is an autosomal recessive disorder. The second group involves genetic disorders of excessive renal phosphate loss (hereditary hypophosphatemic rickets)., Here, we report such rare cases of familial VDDR2A, with alopecia and oral manifestations.
| Case Reports|| |
A 14-year-old male reported to the department with a history of delayed milestones, abnormal movement of head for 2 months and abnormality of knee joint since birth [Figure 1]a. However, he progressively developed marked weakness, gait abnormality, easy fatigability and cramps. He was a product of consanguineous marriage with delayed milestones and delayed teeth eruption. Medical history revealed jaundice immediately after birth and tonsillectomy at the age of 5 years. No abnormality was detected on systemic examination of cardiovascular, respiratory and central nervous system.
Clinical examination revealed sparse eyebrows, drooping of the shoulders and slight deformity of knees with bowing of legs. It also revealed stable vitals, height of 142 cm and weight of 35 kg. Features of stiffening of fingers with severe hypocalcemia (Chvostek's sign and carpopedal spasms) were positive. Alopecia was observed and gives history since birth [Figure 1]b.
Intraoral examination revealed normal mouth opening with competent lips, enamel hypoplasia, dentin defects, dental caries in relation to 36, 37 and erupting 13 [Figure 2]. An orthopantomogram [Figure 3] and [Figure 4] revealed generalized severe enamel hypoplasia, dentin abnormalities, dental caries in relation to 36, 37, erupting 13 and impacted supernumerary teeth in relation to 35, 36 and 45, 46 with enlarged pulp chambers.
|Figure 2: Intraoral examination revealed enamel hypoplasia and dentin defects with dental caries|
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|Figure 3: An orthopantomogram revealed generalized severe enamel hypoplasia, dentin abnormalities|
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|Figure 4: An orthopantomogram revealed mixed dentition with generalized severe enamel hypoplasia|
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Baseline investigations were within normal limit. Severe hypocalcemia (serum calcium: 6.3 mg/dL) and hypophosphataemia (2.1 mg/dL) as well as markedly raised alkaline phosphatase and parathormone levels were observed. Skeletal survey did not reveal features of rickets or osteomalacia. Evaluation for renal tubular acidosis and hypophosphatemic rickets was negative. Levels of Vitamin D metabolites disclosed normal 25-hydroxyvitamin D; however, marked increase in 1,25-dihydroxyvitamin D (1,25[OH]2D) was noted. In our case, the onset of disease at 14 years of age was the absence of response to routine doses of calcium supplements, and the characteristic laboratory abnormalities were compatible with the diagnosis of VDDR2A.
Based on the patient's history, clinical examination and laboratory findings, it is diagnosed as VDDR2. Further, the patient was referred to DNA test which revealed homogeneous missense variation in exon-10 of the VDR gene (chr123:48238786) that results in the amino-acid substitution of cysteine for arginine at codon 393 (p. Arg393Cys; ENST00000550325). Homozygous mutations in the VDR gene were suggestive of VDDR2A.
Similar clinical features were noted in a 5-year-old male patient; intraoral examination showed mixed dentition with enamel hypoplasia, dentin defects and enlarged pulp chambers. Genetic DNA test was suggestive of VDDR2A [Figure 5].
Both the cases were referred to a general physician for further management. They are currently under treatment for Vitamin D deficiency and alopecia. They were also explained about dental problems and their management.
| Discussion|| |
VDDR2 is a rare form of hereditary autosomal recessive disorder, resulting from inactivating homozygous or compound heterozygous mutations in the VDR gene (OMIM*601769), encoding the Vitamin D receptor., It is also known as pseudovitamin D-deficiency Type 2, hypocalcemic Vitamin D-resistant rickets or rickets-alopecia syndrome.
The first case was reported in 1978 by Brooks et al. in a 22-year-old woman with hypocalcemia, secondary hyperparathyroidism, osteomalacia and osteitis fibrosa cystica in association with normal serum 25-hydroxyvitamin D and markedly increased serum 1,25[OH]2D with or without alopecia and named it as VDDR Type II. Due to its rarity, delay in diagnosis and initial treatment, it results in deformities of lower limbs, severe growth retardation, acidotic breathing, cataracts, alopecia and presence of dental abscess.
Rickets is classified based on common etiological factors into two types as calciopenic (defect in metabolism or functions of calcium/deficiency of Vitamin D) or phosphopenic (renal phosphate wasting)., Hereditary rickets is classified into two groups. The first group consists of genetic disorders of Vitamin D biosynthesis and action, such as VDDR1A, VDDR1B, VDDR2A and VDDR2B. The second group involves genetic disorders of excessive renal phosphate loss (hereditary hypophosphatemic rickets)., Common causes of hereditary rickets [Table 1] and various laboratory findings in rickets with different etiology are enumerated [Table 2]. The present cases had alopecia with deformities, laboratory findings and genetic DNA test aides in the diagnosis of VDDR2A.
Clinical features include retarded growth, short stature and bone defects, leading to body deformities, bowing of legs, muscle weakness, convulsions and alopecia. To our knowledge, only a few authors have reported in literature describing the oral manifestations in VDDR2. Oral findings include enamel hypoplasia, dentin defects and dental abnormalities and carious teeth. Dental radiologic features include dentin defects, short roots, large pulp chambers, poorly defined lamina dura, dental abscess and dental caries.,
The present cases reported here were seen with oral manifestations of enamel hypoplasia, dentin abnormalities, dental caries, impacted supernumerary teeth and large pulp chambers.
Management of the VDDR2 includes administering high doses of oral calcitriol (1–6 μg/kg/day in two divided doses) and supplemental calcium (1–3 g/day) for mild to moderate cases. In severe cases, high doses of intravenous calcium infusion give good response, but long-term administration results in complications such as cardiac arrhythmia, hypercalciuria, nephrocalcinosis, catheter related sepsis and extravasation of calcium.,
| Conclusion|| |
Calcium and phosphate metabolism plays a major role in bone mineralization, regulated by parathyroid hormone, 1,25[OH]2D and FGF23. Vitamin D deficiency is an important cause of rickets and is most common. Vitamin D-dependent rickets is another form of bone disorder with rare oral manifestations, which is hereditary in origin, accounting for about 13% of total rickets. Early diagnosis and prompt treatment corrects the disturbed bone metabolism and dental deformities and improves the quality of life.
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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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]