Salivary Metabolites in Patients with Mucopolysaccharidosis

ABSTRACT Objective: To identify the salivary metabolites profile of Mucopolysaccharidosis (MPS) types I, II, IV, and VI patients. Material and Methods: The participants were asked to refrain from eating and drinking for one hour before sampling, performed between 7:30 and 9:00 a.m. Samples were centrifuged at 10.000 × g for 60 min at 4°C, and the supernatants (500µl) were stored at −80°C until NMR analysis. The salivary proton nuclear magnetic resonance (1H-NMR) spectra were acquired in a 500 MHz spectrometer, and TOCSY experiments were used to confirm and assign metabolites. Data were analyzed descriptively. Results: Differences in salivary metabolites were found among MPS types and the control, such as lactate, propionate, alanine, and N-acetyl sugar. Understanding these metabolite changes may contribute to precision medicine and early detection of mucopolysaccharidosis and its monitoring. Conclusion: The composition of low molecular weight salivary metabolites of mucopolysaccharidosis subjects may present specific features compared to healthy controls.

Oral and craniofacial manifestations in a Hunter syndrome patient with hematopoietic stem cell transplantation: A case report.

We described herein the oral and craniofacial features of a 7-year-old boy, diagnosed in utero with mucopolysaccharidosis II (MPS II), who was treated with hematopoietic stem cell transplantation (HSCT) at 70 days of age. The main oral clinical findings were the following: macroglossia, posterior cross-bite, crowding, pointed cuspid teeth, delayed tooth eruption, retained primary teeth, and enamel hypoplasia. The image examination showed: retention eruption, posterior primary teeth with short roots, absence of some permanent teeth, and stretching of the stylohyoid processes bilaterally. This patient showed the importance of early diagnosis and HSCT therapy in attenuating the clinical and radiographic oral and craniofacial manifestations of the MPS II patient.

Condições bucais e metabólitos salivares de pacientes com mucopolissacaridose / Oral conditions and salivary metabolites of patients with mucopolysaccharidosis

Mucopolissacaridose (MPS) é uma doença genética hereditária causada pela deficiência de enzimas lisossômicas que afetam o catabolismo de glicosaminoglicanos, acarretando seu acúmulo em diferentes órgãos e tecidos causando alterações sistêmicas e bucais. O objetivo do estudo foi avaliar e descrever as manifestações bucais e caracterizar os metabólitos salivares de pacientes com MPS e através de relatos de caso investigar as manifestações presentes em pacientes com MPS-II com diferentes tempos de diagnóstico e tratamento. Foram selecionados pacientes de dois Centros de Referência em MPS no Rio de Janeiro (Instituto de Puericultura e Pediatria Martagão Gesteira e Instituto Fernandes Figueira) os quais foram atendidos na Faculdade de Odontologia ­ UFRJ. Treze pacientes portadores de MPS dos tipos I, II, IV e VI foram avaliados quanto às manifestações bucais (tecidos moles, relação oclusal, exame periodontal e dental). Amostras salivares foram coletadas de um paciente de cada tipo de MPS e de um paciente saudável para caracterização dos metabólitos salivares usando espectroscopia de Ressonância Magnética Nuclear. Os dados foram analisados descritivamente (SPSS 23.0) e empregados os testes Fisher e Kruskal-Wallis (p<0,05). A amostra foi composta por 3 pacientes MPS-I, 5 MPS-II, 1 MPS IV e 4 MPS-VI, 4 do sexo feminino e 9 masculino, com idades variando de 2-38 anos. A média de ceo-d/CPO-D variou entre 0-5 e a macroglossia foi a manifestação mais prevalente (61,5%) especialmente no tipo II (p=0,019). O índice de sangramento gengival variou entre os tipos de MPS (p=0,038), maior em pacientes do tipo II. O transpasse horizontal acentuado foi mais prevalente no tipo IV (p=0,005). Foram observadas diferenças nos metabólitos salivares entre os tipos de MPS em relação ao paciente saudável. As manifestações bucais e craniofaciais de pacientes com MPS tipo II com diferentes tempos de diagnóstico e tratamentos foram descritas em dois relatos de casos. Um paciente, gênero masculino, 7 anos de idade com diagnóstico intrauterino recebeu transplante de células-tronco hematopoiéticas aos 70 dias de vida. As principais manifestações bucais e radiográficas foram: macroglossia, mordida cruzada posterior, apinhamento, atraso na erupção, retenção de dentes decíduos, hipoplasia de esmalte, dentes posteriores com raízes curtas e alongamento dos processos estiloides bilateralmente. No segundo relato de caso dois pacientes portadores de MPS-II com diagnóstico tardio apresentaram manifestações craniofaciais e bucais acentuadas, reveladas através do exame tomográfico e avaliação da simetria através da sobreposição de imagens em 3D. Foram observados nesses pacientes: mordida aberta total, arcos dentários expandidos, severa hipoplasia condilar, processos coronoides aumentados além de macroglossia e maloclusão do tipo classe III. Pode-se concluir que a macroglossia e o transpasse horizontal acentuado foram associados respectivamente aos tipos de MPS II e VI. Há evidências da importância do diagnóstico/tratamento precoce na redução das manifestações craniofaciais em paciente com MPS-II. Diferenças nos metabólitos salivares de baixo peso molecular entre paciente saudável e portadores de MPS podem ser promissoras no entendimento da doença. (AU)

Mucopolysaccharidosis (MPS) is a hereditary genetic disease caused by the deficiency of lysosomal enzymes that affect the catabolism of glycosaminoglycans, causing their accumulation in different organs and tissues causing systemic and oral alterations. The objective of the study was to evaluate and describe oral manifestations and to characterize the salivary metabolites of patients with MPS and through case reports we also investigate the manifestations present in patients with MPS-II with different moments of diagnosis and treatment. Patients were selected from two MPS Reference Centers in Rio de Janeiro (Instituto de Puericultura e Pediatria Martagão Gesteira and Instituto Fernandes Figueira), which were attended at the Faculty of Dentistry - UFRJ. Thirteen patients with MPS types I, II, IV and VI were described of oral manifestations (soft tissue, occlusal relationship, periodontal and dental examination). Salivary samples were collected from one patient of each type of MPS as well as healthy ones to characterize the salivary metabolites using Nuclear Magnetic Resonance Spectroscopy. The data were analyzed descriptively (SPSS 23.0) and the Fisher and Kruskal-Wallis tests were used (p <0.05). The sample consisted of 3 MPS-I, 5 MPS-II, 1 MPS IV and 4 MPS-VI, 4 females and 9 males, with ages varying from 2-38 years. Mean of dmft / DMFT varied between 0-5 and macroglossia was the most prevalent manifestation (61.5%), especially type II (p = 0.019). The gingival bleeding index varied among MPS types (p = 0.038), higher in type II patients. The accentuated horizontal transpiration was more prevalent in type IV (p = 0.005). Differences were observed in salivary metabolites between MPS types in relation to the healthy patient. The oral and craniofacial manifestations of patients with MPS type II with different moments of diagnosis and in addition the treatment were described in two case reports. A 7-year-old male patient with intrauterine diagnosis received hematopoietic stem cell transplantation at 70 days of age. The main oral and radiographic manifestations were: macroglossia, posterior crossbite, crowding, delayed eruption, retention of deciduous teeth, enamel hypoplasia, posterior teeth with short roots and stretching of styloid processes bilaterally. In the second case report, two patients with MPS-II with late diagnosis showed marked craniofacial and buccal manifestations revealed by tomographic examination and evaluation of symmetry through the overlapping of 3D images. These patients were: total open bite, expanded dental arches, severe condylar hypoplasia, increased coronoid processes in addition to macroglossia and class III malocclusion. We concluded that the macroglossia and the accentuated horizontal transpiration were associated respectively with the MPS II and VI types. The importance of early diagnosis / treatment in the reduction of craniofacial manifestations in patients with MPS-II has been demonstrated. Differences in low molecular weight salivary metabolites between healthy and MPS patients may be promising on understanding this disease. (AU)