Dental considerations in a paediatric patient with Diamond-Blackfan anaemia
- Imam Azam ,
- Morankar Rahul ,
- Nitesh Tewari and
- Kalpana Bansal
- Division of Pedodontics and Preventive Dentistry, Center for Dental Education and Research, AIIMS, New Delhi, India
- Correspondence to Dr Morankar Rahul; captainrahul88@gmail.com
Abstract
Diamond-Blackfan anaemia (DBA) is a rare genetic disorder characterised by a decrease in the production of red blood cells due to bone marrow malfunction. The estimation of disease occurrence is approximately 1 in 100 000–2 00 000 live births. This paper presents the case of a 7-year-old male child diagnosed with DBA at the age of 4 months. The diagnosis was established with haematological findings, bone marrow biopsy and molecular testing. The case was managed successfully for dental symptoms without any complication.
Background
Diamond-Blackfan anaemia (DBA) is one of the rare group of genetic disorders, known as the inherited bone marrow failure syndromes.1 Josephs first reported this condition and later completely described by Diamond and Blackfan.2 3 DBA is a rare disorder of genetic origin characterised by bone marrow malfunction resulting in failure to make enough red blood cells. It usually becomes apparent during the first year after birth with a clinical presentation of anaemia.4 This disease is estimated to occur in 1 out of 100 000–2 00 000 live births.5 The autosomal dominant inheritance is the most common, with variable penetrance. However, the x-linked pattern of inheritance of some genes explains the heterogeneous character of the disorder.6
Haematological presentation of the disorder is characterised by normochromic or macrocytic anaemia, deficiency of red cell precursors, decreased reticulocyte count, normal or reduced leucocyte counts and normal or reduced platelet counts.7–9 The common physical findings include short stature, extremely blonde white hair, snub nose, small head, pointed chin, some skeletal abnormalities such as polydactyly and hypoplastic limbs. About one-third of cases with DBA are also associated with congenital cardiac and urogenital abnormalities.6 7 10 About 3%–10% of these cases have cleft lip and palate, whereas microstomia, microdontia and deficient jaw growth are also evident in some.11 12 Haematology and bone marrow biopsy are the common investigations done for the diagnosis of DBA. Mutation of ribosomal protein-S19 (RPS-19) can also be seen in 20%–25% of these patients on genetic testing.13 The diagnostic and supporting criteria accepted for DBA diagnosis have been described in table 1.
Diagnosis of Diamond-Blackfan anaemia
| Diagnostic criteria | |
|
|
| Supporting criteria | |
| Major | Minor |
|
|
Case presentation
A 7-year-old boy with his parents reported to the Outpatient Department of Paediatric Dentistry with the chief complaint of decayed maxillary left posterior teeth (Federation Dentaire Internationale (FDI) notation 64, 65). The parents noticed the tooth decay about 4–5 months ago but did not report for treatment. According to the parents, child had complaint of food lodgement with no pain or discomfort. He was their first child born from the non-consanguineous marriage. (figure 1) The child was diagnosed with the DBA at the age of 4 months. The diagnosis was established based on the clinical examination, haematological findings, bone marrow investigations and molecular analysis. The mother also had a history of anaemia of unknown origin since childhood; however, the other sibling(a younger brother) was unaffected (figure 1).
Pedigree chart.
Physical examination of the child revealed short stature with an asthenic body, small head, microstomia and polydactyly in the upper right limb. The extraoral examination also revealed leptoprosopic facial form, malar prominence, convex profile with competent lip and pointed chin (figure 2A–C). Intraoral examination revealed the light pink colour of gingiva with melanin pigmentation, slightly pale hard palate with prominent rugae in the anterior palate region. Dental hard tissue had deep proximal carious lesions with the involvement of tooth (FDI notation 64, 65). Maxillary central incisors (FDI notation 51, 61) had enamel breakdown on the mesial surfaces (figure 3A,B).
(A) Extraoral frontal view. (B) Extraoral lateral view. (C) Polydactyly with right hand.
(A) Preoperative maxillary occlusal view. (B) Preoperative periapical radiograph. (C) Postoperative maxillary occlusal view. (D) Postoperative periapical radiograph. Excess cement was removed during follow-up visit.
Investigations
Haematological investigations were suggestive of decreased haemoglobin (4.8 gm/dL), decreased red cell count (3.73×106/µL), elevated mean corpuscular volume (106.8 fL), decreased white cell count (4.79×103/µL), increased platelet count (583×103/µL) and decreased reticulocyte count (0.1%). Bone marrow aspiration revealed pure red cell aplasia with decreased erythropoietic cells. Molecular genetic testing comprised of gene sequence analysis of ribosomal proteins (RPs) of DBA showed mutation with a change in amino acids of RPs on chromosome numbers 1, 6, 11 and 14 (chr1-RPS6KC1, chr6-RPS6KA2, chr11-RPS6KA4, chr11-RPS6KB2 and chr14-RPS6KL1). An intraoral periapical radiograph revealed a radiolucency approaching the pulp both in teeth 64 and 65 (FDI notation).
Differential diagnosis
Transient erythroblastopenia of childhood (TEC), Fanconi anaemia, parvovirus infection and megaloblastic anaemia (table 2).
Differential diagnosis of Diamond-Blackfan anaemia
| Conditions | Clinical presentation | Haematological findings | Family transmission/genetic alteration |
|---|---|---|---|
| Parvovirus B19 Infection |
|
|
A pregnant mother may infect the baby |
| Fanconi anaemia (FA) |
|
|
|
| Transient erythroblastopenia | Patients are usually healthy with common signs of anaemia | Temporary suppression of erythropoiesis results in moderate to severe normochromic normocytic anaemia |
|
| Megaloblastic anaemia |
|
Bone marrow produces immature red cells that are usually large and structurally abnormal | None |
Treatment
The patient had received several blood transfusions after the diagnosis along with oral steroids (prednisolone 2 mg/kg/day) till the age of 5 years. Since then, blood transfusion had stopped completely and child is on oral prednisolone (1 mg/kg/day). A thorough clinical evaluation of the oral cavity was performed, as well as a detailed history was taken as there is a high likelihood of neoplasms in these cases. The haematological assessment was done before the dental treatment, which was found normal and the patient was advised to continue his routine oral steroid therapy. Dental caries with 51 and 61 was managed with composite restorations. Mineral trioxide aggregate pulpotomy was done with tooth 65, whereas pulpectomy was performed in tooth 64 followed by stainless steel crown (figure 3C,D).
Follow up
The patient was recalled for follow-up at every 3-month interval. At the 18 month recall, the patient had no signs and symptoms either related to his general condition or oral symptoms (figure 4). The patient is currently continuing the oral steroids (1 mg/kg/day).
Clinical presentation after 18 months.
Discussion
This paper presents the dental management in a case of DBA. The patient was diagnosed and managed for DBA-related symptoms via a multidisciplinary approach in the department of neonatology, paediatrics and paediatric haematology. The diagnosis of the condition is difficult due to its rare and multifaceted clinical presentation. DBA many times is misdiagnosed with TEC. It is a postinfectious, IgG-mediated transient autoimmune disorder with pure red cell aplasia. It occurs in children as a result of infections.18 The presence of red cell aplasia in children younger than 1 year suggests more likelihood of DBA, which is predominantly an inherited disorder. It is characterised by the presence of congenital anomalies, fetal haemoglobin, elevated Mean Corpuscular Volume (MCV) and erythrocyte adenosine deaminase activity.19 20 Genetic workup plays a key role in diagnosis, as DBA is frequently caused by a mutation in RPS-19.21 Although DBA and Treacher Collins syndrome both share similarities, they can be differentiated based on haematological findings, missing of lower lid coloboma and absence of TCOF1 mutations.11 Age of onset, decreased red cell count, macrocytosis, decreased erythroid precursors, positive family history and mutation of RP genes, and absence of any other bone marrow suppressive disorder were the key determinants in the diagnosis of the present case.
Genotype and phenotype correlations have been established in various studies; however, no correlation has yet been found between DBA genes, haematological severity and response to steroids.13 An increased probability of cardiac, thumb and craniofacial anomalies are linked to mutations of RPL5 or RPL11.22–24 Along with mutations of RPL5 or RPL11, an accompanying mutation of RPS-19 can be found in cases with skeletal deformations.25 Patients with RPL5 mutations show cleft palate malformations, whereas those with a mutation in RPL11 shows the cleft lip or palate.26 The finding of an affected thumb in the present case was not exactly as per the phenotypes reported by Gazda et al. who found RPL5 and L11 mutations were associated with cleft palate and abnormal thumbs in patients with DBA. The protein genes affected in the present case were RPS6KC1, RPS6KA2, RPS6KA4, RPS6KB2 and RPS6KL1.22 The clinical manifestations seen in the present case are very mild compared with those reported in the literature. This can be attributed to the genetic alterations in those RP genes that previously is not associated with the disease, whereas genes associated with the severe phenotypic form were found unaffected in the present case. It has been also found that the occurrence of any solid tumour or leukaemia is 5.4-fold higher in patients with DBA than expected in a demographically matched comparison with the general population.27
There is a lack of literature about the oral and dental findings in DBA with some cases reporting severe gingivitis and multiple carious teeth. Poor healing of tooth extraction sites, presence of supernumerary teeth, impacted third molars and obliteration of the coronal pulp chambers are the other features reported (table 3).11 28–35
Oral manifestations and dental findings of Diamond-Blackfan anaemia reported in the literature
| Author | Year | Oral manifestations reported |
|---|---|---|
| Sanger and Wilson 28 |
1982 | Severe gingival inflammation, multiple decayed teeth and poor healing of tooth extraction sites. |
| Willis and Seale 29 | 1984 | Multiple carious and supernumerary teeth requiring frequent dental treatment. Poor oral hygiene with generalised marginal gingivitis. Radiographic findings revealed complete obliteration of pulp chamber in multiple teeth. |
| Gripp et al11 | 2001 | Craniofacial abnormalities described as ear deformities, cleft palate and underdevelopment of midface and lower jaw. |
| Handler et al31 | 2009 | Micrognathia and cleft palate with obstructive breathing. Radiographic findings were suggestive of mandibulofacial dysostosis and choanal atresia. |
| Ozden et al30 | 2011 | Class III malocclusion with narrow maxilla and crossbite. Cleft palate along with the cardiac anomalies. Impacted third molars and dental caries with multiple teeth with poor oral hygiene. |
| Gomez and Munerato32 | 2016 | Painful crateriform ulceration covered with pseudomembrane on lower labial mucosa subsequent to long-term corticosteroid therapy. |
| Ozcan et al33 | 2017 | Severe dental caries and mediocre oral hygiene. |
| De Kock et al34 | 2019 | Vertical maxillary hyperplasia, protrusion of upper lip and gummy smile. Angle’s class II malocclusion with anterior open bite and eversion of lower incisors. Pulp stones with multiple teeth. Disproportional head size with frontal bossing and flat nasal bridge. |
| Shanthi et al35 | 2019 | True anodontia with all the permanent tooth buds missing in maxillary and mandibular arches and poorly developed maxillary and mandibular alveolar ridge. |
Footnotes
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Contributors IA and MR involved in concept, design, review of literature, preparation, revision of manuscript and patient care. NT involved in design, review of literature, preparation and revision of manuscript. KB involved in preparation and revision of manuscript.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Patient consent for publication Parental/guardian consent obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
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