Oral Findings of Children, Adolescents and Young Adults Affected by Muccopolysaccharidosis

INTRODUCTION

Mucopolysaccharidosis (MPS) comprises of a set of rare inherited lysosomal disorders caused byenzyme deficiency resulting in disturbances in the catabolism of glycosaminoglycans (GAGs). This leads to increased storage of GAGs in the lysosomes in various tissues throughout the body.¹ The phenotypic presentation is extensive and is dependent on the type of GAGs stored. GAGs form an integral part of the ground substance of various connective tissue and play a poignant role in the development and regulation of various tissues like teeth, bones and cartilage. They also play a vital role in the functioning and maintenance of organs like liver and spleen and organ system mainly skeletal, respiratory, central nervous & cardiovascular system.^2.3 MPS are classified into seven different subsets depending on the deficient enzyme and the GAGs accumulated (Table 1).^1,3 The aetiology of MPS is a recessive gene inheritance with the exception of MPS II, which is X-linked.²

The advent of enzyme therapies has revolutionised the medical management of MPS disorders which substantially prolongs the life expectancy and the interim quality of life. As a major contributor to quality of life, the management of the oral health of these patients is becoming increasingly important.⁴

There is limited literature regarding the oral health of these patients, provided by sporadic case reports and epidemiological studies of small cohorts³ . Thus, the aim of this study was to systematically record the oral findings of patients diagnosed with MPS and subsequently assess their oral health needs.

MATERIALS AND METHODOLOGY

A cross- sectional study was conducted in the institution from May 2018 to June 2019. Ethical clearance was obtained from the teaching institution and hospital and an informed consent was obtained from parents/guardian for the patients who participated in the study. Due to practical constraints, the oralexamination was performed under artificial lighting, either on a hospital trolley or in the wheelchair. Children who were very uncooperative were excluded from the study. Oral examination was done with the help of sterile mouth mirrors and explorers. Complete soft tissue and hard tissue examination was done and the findings recorded. DMFT or def indices were recorded in accordance with WHO criteria and methods.

RESULTS

Sixty-four patients agreed to partake in the study, of which seven patients were excluded from the study due to severe behavioural issues (n=57). Table two shows the general characteristics of the participants.Table three shows the general growth characteristics of the subjects. Table four illuminates the common extra/ intraoral findings in the study participants. Tablefivearrays the subsets of the MPS and the number of participants with carious lesions with majority of the participants (87.7%) having had carious experiences. Table six illustrates the gingival health of the participants.

DISCUSSION

In the present study, a cohort of 57 patients from various parts of the Indian subcontinent were included with six pairs of affected siblings. The diagnosis of the patients was confirmed by both exome sequencing and biochemical tests for the accumulated GAGs/ deficient enzyme. The patients partaking in the study were from 2-22 years of age with majority of them (80.7%) having history of first/ second degree consanguineous marriage in their pedigree. Although consanguinity does not increase the allele frequency of common disorders, it increases the probability of mating between two individuals heterozygous for the same mutant allele.⁵ This has contributed to increased burden of rare genetic diseases especially autosomal recessive disorders like MPS. However, the disease manifestation could also be due to sporadic mutation in a child born to unrelated non-carrier parents.⁶

The present study showed that MPS I(64.7%), MPS II (100%) and MPS III(100%) manifested mental retardation supporting the previously conducted studies.^7,8 Out of the 17 patients diagnosed with MPS I, six patients did not manifest mental retardation as one case was an attenuatedform of MPS I; three two-year old patients who manifested no symptoms of the disease but were evaluated due to their siblings’ diagnosis and two of the patients were under long term enzyme replacement therapy.

In contrast to previous studies wherein MPS III (1:70,000) was the more prevalent followed by MPS 1 (1:100000-115000), in the present study prevalence of MPS IV was found to be higher.^9,10 This discrepancy is likely because of overlapping phenotypic features due to the vast clinical heterogeneity of signs and symptoms in each subset of MPS and limited diagnostic facility for the accurate investigations in most of the centres in the country. Moreover, the economic factor plays a poignant role in the confirmatory tests. The incidence of Hunters’ syndrome was predominantly in males as corroborated in the previous studies owing to its X linked inheritance.⁷

The extraoral findings commonly observed in patients who partook in the study are substantiated by previous literature.^11-12 All the MPS IV patients in the study had atlanto-axial dysfunction and were scheduled to or had already undergone surgery for correction.Dental health care professionals must be aware that these patients require neck support during treatment. The present study bolstered the finding that patients with MPS have enlarged adenoids and macroglossia due to deposition of GAGs resulting in development of habits like obstructive mouth breathing and tongue thrusting.^11,12 The twelve patients who didn’t report with mouth breathing of which four patients were two-year olds who were diagnosed in routine genetic assay as their siblings were known cases of MPS; three patients had undergone adenoidectomy due to severe respiratory obstruction and attenuated form of MPS IV and MPS I. Mouth breathing can be attributed to the development of high arched palate and incompetent lips.¹³ Similarly, the macroglossia can result in tongue thrusting which subsequently proceeded to development of anterior open bite. Furthermore, these non-nutritive habits result in development of posterior crossbite.¹⁴ During the development of teeth deposition of the GAGs causes disturbances in the formation of enamel resulting in disturbances like hypoplastic lesions and thinner enamel especially in MPS IV. This finding was ratified with the results in present study. The study showed that majority of the participants having had high caries prevalence which was consistent with studies by Ponciano et al15 and Mc Govern et al.¹⁶ This could be ascribed to the hyposalivation¹⁵; mouthbreathing¹⁷; xerostomia causing medicaments for cardiac ailments like calcium channel inhibitors¹⁸; increase in Streptococcus mutans and Candida sp¹⁵; alterations in immune system¹⁹; reduction in pH¹⁵ and vitamin D deficiency.²⁰ The MPS patients presented with morphological and physiological changes both extraorally and intraorally making dental care very critical. Though the patients presented with higher caries rate and poor oral hygiene, there was a very lower number of filled teeth, revealing neglected dental care. There is an evident need to educate and motivate not only patients but also their parents or legal guardians to ensure the improvement of oral hygiene routines. Dental treatment must be integrated into the multidisciplinary management in order to improve the quality of life of patients and their families. It is important to encourage regular visits to dentists, in order to avoid complex invasive treatments. Treatment should be based on a preventive protocol promoting the use of pit and fissure sealants, fluoride, dietary control and good oral hygiene habits. Moreover, parents must be made aware of the role of habit breaking appliances and their effect on the growing craniofacial structures.

CONCLUSION

In conclusion, patients diagnosed with MPS have significantly higher oral health care needs due to morphological, anatomical, and physiological changes. Moreover, they have poor oral hygiene and are at a higher risk of dental caries. Hence, regular and periodic check-up should become an integral part of the patient’s management for a better quality of life for patients and their families. The rationale of the treatment should be based on preventive protocol promoting the use of pit and fissure sealants, topical fluoride therapy, dietary control and good oral hygiene practises.