Diet plays an integral role in the maintenance of oral health. Dietary modifications due to medical problems such as PKU, in which therapeutic dietary practices are similar to MSUD, can have adverse effects on oral health. In the long run, the artificial composition of the consumed foods may have adverse consequences on health, including micronutrient or essential amino acid deficiencies, obesity, and reduced bone mineral density [24]. However, potential effects of the artificial diet on oral health of MSUD patients have not been extensively studied [13].
In the present study, a higher prevalence of dental caries was recorded in patients with MSUD under 12 years of age, compared to that obtained from a different study in healthy Turkish children (82.3% vs. 61%, respectively) [25]. As reported in the study of Topaloğlu et al. [26], a virtual palliative, preventive and restorative care is urgently required in juvenile oral healthcare in Turkey.
In 1989, Gazit et al. reported oral manifestations of a 14-year-old patient with MSUD [13]. They observed remarkable gingival inflammation, multiple rampant caries lesions mainly attributed to high carbohydrate MSUD diet, soft tissue and bone necrosis (alveolar osteomyelitis). The authors suggest that chronic destructive inflammatory process in the gingiva and local factors such as poor oral hygiene, heavy calculus formation, and severely decayed teeth could have possibly caused soft tissue and bone necrosis. Osteomyelitis is an uncommon but well-recognized complication of untreated odontogenic infection [27]. We did not encounter such a severe consequence of untreated caries in our patients.
Since there has been no other report on oral health indices of patients with MSUD, we could only compare the oral health results of MSUD with the data of patients with PKU. Studies evaluating the oral health status of children with PKU are few and have conflicting results [10,11,12]. Most studies in children with PKU have revealed a similar or lower prevalence of caries compared to healthy children. A low rate of caries despite a highly cariogenic diet might result from high phenylalanine (the accumulating amino acid in PKU), which has been considered to possibly act as a factor that limits the growth of plaque microorganisms [10, 11]. In a study performed at the same clinic, we have reported the prevalence of dental caries in 132 well-treated PKU patients as 67% [12]. Although dental caries in MSUD patients was higher than the PKU patients in that study; these differences might be attributed to the oral health behaviors, diet, and concomitant diseases such as epilepsy or intellectual disorders. It was reported in a previous study that intellectual performance of children with MSUD patients was significantly lower than that of a matched cohort of early treated PKU patients [28].
In a systematic review and meta-analysis regarding breastfeeding and dental caries; it was reported that breastfeeding up to 12 months of age is not associated with an increased risk of dental caries and in fact may provide some protection compared to formulas [29]. However, children breastfed for more than 12 months had an increased risk of dental caries due to prolonged breastfeeding, nocturnal feeding during sleep, cariogenic foods and drinks in the diet, or poor oral hygiene. In this study, most of our patients were breastfed for less than a year. Nocturnal feeding and no toothbrushing were present in more than half of the patients.
To the best of our knowledge, there has been no report of radiological findings in patients with MSUD in the literature. In the present study, panoramic radiographs revealed multiple abnormalities as shown in Table 3. Aberrant mandibular premolars, which were detected in two patients, is an uncommon anomaly of the root canal morphology indicating the presence of more than one canal in mandibular premolars. Aberrant root canal anatomy of mandibular premolars presents an endodontic challenge to successful treatment. There is an also increased probability of root fracture if such teeth are subjected to rotation during extraction [30]. It is important to be able to determine the morphology of these teeth radiologically and obtain a thorough knowledge of root canal anatomy and possible variations [31]. Seven out of 12 panoramic images had alterations in the temporomandibular joint or coronoid process. Although panoramic images could not be obtained in all of the patients due to intellectual disability or uncooperative behavior, given these images, possible temporomandibular symptoms such as restricted mouth opening, the clicking sound in temporomandibular joints should be considered in clinical examinations [32].
MSUD may be fatal if not treated, but once effective treatment is provided, long-term survival is good. However, intellectual impairment is frequently encountered in affected children [28]. It was reported that people with intellectual impairment are more likely to have poor oral hygiene and periodontal disease, and are possibly more likely to have caries than people without intellectual impairment [33, 34]. In this study, prevalence of intellectual disability, dental caries, and plaque index scores was found to be high which was in accordance with the current knowledge.
Children who have chronic conditions, intellectual disabilities, or other health problems are referred to as “children with special health needs”. Oral health is critical to good systemic health, especially in children with special health needs. Consequences of MSUD and its treatment have physical and psychological effects on children and their families, such as poor growth due to the restricted lifelong diet, motor disorders, and neurocognitive disorders [35, 36]. In a study regarding the health-related quality of life of the children and the parents of children affected with organic aciduria, urea cycle defects, or MSUD; the altered ‘physical’ and ‘social’ quality of life scores were comparable with patients with leukemia and their families [35]. In our study, fourteen patients had pain associated with dental caries. More than half of the parents did not receive an education after primary school level and reported making minimum wage. It has been reported that untreated dental caries with associated toothache have negative effects on weight gain, growth, and quality of life, as well as the cognitive development of young children [37]. The health-related quality of life of the parents and better care for their children could be managed by providing education and psychosocial support, which could also potentially improve dental health [38].
It was difficult to include a matched control group in this study because a lot of confounding factors were present, such as socioeconomic status of parents, dietary restrictions, intellectual disability and concomitant diseases. Although the sample size may seem small, which may be regarded as a limitation, and may not represent the oral health status of the whole MSUD population, it is also quite large for such a rare disease in a single center. Prospective cohort studies in larger samples, including children with MSUD and matched control groups may be necessary to clarify the further interaction between MSUD and oral health.