Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contact Us Login 
An Official Publication of the Indian Association of Oral and Maxillofacial Pathologists


 
  Table of Contents    
CASE REPORT - MISCELLANEOUS  
Year : 2019  |  Volume : 23  |  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 Submission13-Dec-2018
Date of Acceptance16-Jan-2019
Date of Web Publication22-Feb-2019

Correspondence Address:
Moni Thakur
Department of Oral and Maxillofacial Pathology, Mamata Dental College and Hospital, Giriprasad Nagar, Khammam - 507 002, Telangana
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jomfp.JOMFP_309_18

Rights and Permissions

 

   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 2019 May 24];23, Suppl S1:130-3. Available from: http://www.jomfp.in/text.asp?2019/23/4/130/252731





   Introduction Top


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.[1],[2] 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).[2],[3]

In addition, genetic causes of rickets (hereditary rickets) are rare, accounting for about 13% of total rickets.[4] 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.[5] The second group involves genetic disorders of excessive renal phosphate loss (hereditary hypophosphatemic rickets).[6],[7] Here, we report such rare cases of familial VDDR2A, with alopecia and oral manifestations.


   Case Reports Top


Case 1

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.
Figure 1: (a and b) Profile picture with sparse hair

Click here to view


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

Click here to view
Figure 3: An orthopantomogram revealed generalized severe enamel hypoplasia, dentin abnormalities

Click here to view
Figure 4: An orthopantomogram revealed mixed dentition with generalized severe enamel hypoplasia

Click here to view


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.

Case 2

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].
Figure 5: Profile picture with sparse hair

Click here to view


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 Top


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.[1],[8] It is also known as pseudovitamin D-deficiency Type 2, hypocalcemic Vitamin D-resistant rickets or rickets-alopecia syndrome.[9]

The first case was reported in 1978 by Brooks et al.[10] 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.[10] 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.[11]

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).[2],[3] 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.[5] The second group involves genetic disorders of excessive renal phosphate loss (hereditary hypophosphatemic rickets).[6],[7] Common causes of hereditary rickets [Table 1] and various laboratory findings in rickets with different etiology are enumerated [Table 2].[1] The present cases had alopecia with deformities, laboratory findings and genetic DNA test aides in the diagnosis of VDDR2A.
Table 1: Common causes of hereditary rickets

Click here to view
Table 2: Various laboratory findings in rickets with different etiology

Click here to view


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.[12] 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.[12],[13]

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.[1],[14]


   Conclusion Top


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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Angham AM, Rajaa A. Types of rickets. Ann Orthop Rheumatol 2017;5:1085.  Back to cited text no. 1
    
2.
Sperling M. Pediatric Endocrinology. 4th ed. Philadelphia: Saunders/Elsevier; 2014.  Back to cited text no. 2
    
3.
Rudolph CD, Rudolph AM, Lister GE, First LR, Gershon AA. Rudolph's Pediatrics. 2nd ed. New York: McGraw-Hill. 2011.  Back to cited text no. 3
    
4.
Beck-Nielsen SS, Brock-Jacobsen B, Gram J, Brixen K, Jensen TK. Incidence and prevalence of nutritional and hereditary rickets in Southern Denmark. Eur J Endocrinol 2009;160:491-7.  Back to cited text no. 4
    
5.
Miller WL. Genetic disorders of Vitamin D biosynthesis and degradation. J Steroid Biochem Mol Biol 2017;165:101-8.  Back to cited text no. 5
    
6.
Bastepe M, Jüppner H. Inherited hypophosphatemic disorders in children and the evolving mechanisms of phosphate regulation. Rev Endocr Metab Disord 2008;9:171-80.  Back to cited text no. 6
    
7.
Acar S, Demir K, Shi Y. Genetic causes of rickets. J Clin Res Pediatr Endocrinol 2017;9:88-105.  Back to cited text no. 7
    
8.
Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Nelson Textbook of Pediatrics. 18th ed. Saunders, Iceland: Elsevier/Saunder; 2010; pp. 253-62.  Back to cited text no. 8
    
9.
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.  Back to cited text no. 9
[PUBMED]  [Full text]  
10.
Brooks MH, Bell NH, Love L, Stern PH, Orfei E, Queener SF, et al. Vitamin-D-dependent rickets type II. Resistance of target organs to 1, 25-dihydroxy Vitamin D. N Engl J Med 1978;298:996-9.  Back to cited text no. 10
    
11.
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.  Back to cited text no. 11
  [Full text]  
12.
Zambrano M, Nikitakis NG, Sanchez-Quevedo MC, Sauk JJ, Sedano H, Rivera H, et al. Oral and dental manifestations of Vitamin D-dependent rickets type I: Report of a pediatric case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:705-9.  Back to cited text no. 12
    
13.
Souza AP, Kobayashi TY, Lourenço Neto N, Silva SM, Machado MA, Oliveira TM, et al. Dental manifestations of patient with vitamin D-resistant rickets. J Appl Oral Sci 2013;21:601-6.  Back to cited text no. 13
    
14.
Celbek G, Gungor A, Albayrak H, Kir S, Guvenc SC, Aydin Y, et al. Bullous skin reaction seen after extravasation of calcium gluconate. Clin Exp Dermatol 2013;38:154-5.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
Print this article  Email this article
            

    

 
   Search
 
  
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
  Related articles
    Article in PDF (1,204 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Introduction
   Case Reports
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed163    
    Printed4    
    Emailed0    
    PDF Downloaded22    
    Comments [Add]    

Recommend this journal

Journal of Oral and Maxillofacial Pathology | Published by Wolters Kluwer - Medknow
Online since 15th Aug, 2007