Dental and Endodontic Management in a Patient with Familial X-Linked Hypophosphatemic Rickets

ABSTRACT: The term rickets refers to insufficient or retarded mineralization of the osteoide matrix. X-linked hypophosphatemic (XLH) rickets is a rare genetic disorder characterized by biochemical changes in bone mineralization due to inactivation of the phosphate regulating gene and primary defect of the osteoblasts. The aim of this article was to report a clinical case of XLH, its oral manifestations, periapical changes and dental management. A 31-year old woman female patient was referred to the school of dentistry with pain and sensitivity in the teeth. She had a childhood history of rickets, hypophosphatemia and alteration in Vitamin D. In the oral exam, enamel hypoplasia, microdontia, fistula, caries and periapical lesions and periodontal disease were diagnosed. The radiographic and tomographic exams exhibited the presence of periapical lesions involving various teeth with radiolucent images, suggestive of granuloma or periapical cysts. The treatme nt prioritized the urgency of eliminating pain and removing the foci of infection. Endodontic treatment began in the teeth that had fistula or periapical lesions and in parallel, oral hygiene guidance was provided and periodontal treatment was performed. There was an improvement in the clinical condition with reduction in inflammation and mobility of the teeth. Dentists and health professionals must evaluate the patient as a whole, considering the relations between systemic and oral health. Knowledge of systemic diseases associated with rickets and their characteristics is essential for making a correct oral diagnosis and planning the dental treatment.

RESUMEN: El término raquitismo se refiere a la mineralización insuficiente o retardada de la matriz osteoide. El raquitismo hipofosfatémico ligado al cromosoma X (XLH) es un trastorno genético caracterizado por cambios bioquímicos en la mineralización ósea debido a la inactivación del gen regulador del fosfato y al defecto primario de los osteoblastos. El objetivo de este artículo fue reportar un caso clínico de XLH, sus manifestaciones orales, cambios periapicales y manejo dental. La paciente, una mujer de 31 años, acudió a la Clínica de Semiología de la UFPR con dolor y sensibilidad en varios dientes. Tenía antecedentes infantiles de raquitismo, hipofosfatemia y alteración de la vitamina D. En el examen oral se diagnosticó hipoplasia del esmalte, microdoontia, fístula, caries y lesiones periapicales y enfermedad periodontal. Los exámenes radiográficos y tomográficos mostraron la presencia de lesiones periapicales en varios dientes con imágenes radiolúcidas, sugestivas de granuloma o quistes periapicales. El tratamiento priorizó la urgencia de eliminar el dolor y remover los focos de infección. Se inició tratamiento de endodoncia en los dientes que presentaban fístula o lesiones periapicales y paralelamente se brindó orientación de higiene oral y se realizó tratamiento periodontal. Hubo una mejoría en la condición clínica con reducción de la inflamación y movilidad de los dientes. Los odontólogos y profesionales de la salud deben evaluar al paciente como un todo, teniendo en cuenta las relaciones entre salud sistémica y oral. El conocimiento de las enfermedades sistémicas asociadas al raquitismo y sus características es fundamental para realizar un correcto diagnóstico oral y planificar el tratamiento odontológico.

Growth in height and body proportion from birth to adulthood in hereditary hypophosphatemic rickets: a retrospective cohort study.

PURPOSE: Patients with hereditary hypophosphatemic rickets are short and disproportionate and very little information is available on segmental growth, but the body disproportion at adulthood leads us to think that the growth velocity of legs is slower. METHODS: A total of 96 children were included and molecular testing was carried out in 42. Children who reached adult height were classified into two groups according to their compliance to conventional treatment (phosphate supplement and calcitriol). Individual growth records of height and sitting height/height were plotted using Argentine reference data in 96 children and growth curves were estimated by fitting Preece-Baines Model 1 in 19 of the children. RESULTS: Molecular testing revealed sequence deleterious alterations or large deletions in 36/42 patients. During childhood, 76% of children grew below - 1.88 standard deviation score (SDS) and 97% had body disproportion. During adolescence, the mean peak height velocity for the good and poor compliance to treatment groups was 7.8 (0.6) and 5.4 (0.4) cm/year in boys and 7.0 (0.7) and 5.2 (0.8) cm/year in girls, respectively. At adulthood, the median sitting height/height ratio was 2.32 and 6.21 SDS for the good and poor compliance to treatment groups, respectively. The mean pubertal growth spurt of the trunk was -0.8 (1.4) SDS, with a short pubertal growth spurt of - 1.8 (0.4) SDS for limbs in the good compliance group. Median adult height in 13/29 males and 30/67 females was -4.56 and -3.16 SDS, respectively. CONCLUSION: For all patients the growth spurt was slower, secondary to a short growth spurt of limbs, reaching a short adult height with body disproportion that was more prominent in the poor compliance group.

A pathogenic PHEX variant (c.1483-1G>C) in a Korean patient with X-linked hypophosphatemic rickets.

X-linked hypophosphatemic rickets is an X-linked dominantly inherited disorder characterized by defects in renal phosphate transport leading to phosphate wasting and hypophosphatemia. In this report, we describe a case of X-linked hypophosphatemic rickets in a patient with a rare pathogenic PHEX variant. The 25-year-old female patient came to our clinic for genetic counseling regarding presumed genetic disease and pregnancy. When she was 9 years old, she had been diagnosed with vitamin D-resistant rickets based on laboratory results and symptoms. She had undergone orthopedic surgery due to bowing leg deformities. Since then, she was intermittently self-prescribing oral phosphate and calcium supplements. At 25 years old, she was diagnosed with X-linked hypophosphatemic rickets with a rare pathogenic PHEX variant (c.1483-1G>C) by next-generation sequencing. This is the second report of the c.1483-1G>C variant to date, and her pathogenicity was confirmed based on the most recent guideline. Traditionally, the disease had been diagnosed mostly based on clinical findings. However, with advancements in genetic testing, genetic confirmation has become an imperative part of diagnostic workup. Herein, we report a 25-year-old female Korean patient diagnosed with X-linked hypophosphatemic rickets harboring a rare pathogenic PHEX variant.

Vitamin D-dependent rickets (VDDR) type 1: case series of two siblings with a CYP27B1 mutation and review of the literature / Raquitismo dependente de vitamina D: tipo 1: série de casos de dois irmãos com mutação CYP27B1 e revisão da literatura

Abstract Two siblings presented with clinical and biochemical features of rickets, initially suspected as hypophosphatemic rickets. There was no improvement initially, hence the siblings were reinvestigated and later diagnosed as having vitamin D-dependent rickets (VDDR) type 1 due to a rare mutation in the CYP27B1 gene encoding the 1α-hydroxylase enzyme. Both siblings improved with calcitriol supplementation. The initial presentation of VDDR is often confusing and algorithmic evaluation helps in diagnosis. We also present a brief review of the literature, including genetics.

Resumo Dois irmãos apresentaram características clínicas e bioquímicas do raquitismo, com suspeita clínica inicial de raquitismo hipofosfatêmico. Não houve melhora no início, portanto os irmãos foram reavaliados e, posteriormente, diagnosticados com raquitismo dependente de vitamina D (VDDR) tipo 1 devido a uma rara mutação no gene CYP27B1, que codifica a enzima 1a-hidroxilase. Ambos os irmãos melhoraram com a suplementação de calcitriol. A apresentação inicial do VDDR geralmente é confusa e a avaliação algorítmica ajuda no diagnóstico. Também apresentamos uma breve revisão da literatura, incluindo genética.

Enamel and dentin mineralization in familial hypophosphatemic rickets: a micro-CT study.

OBJECTIVES: The aim of the present study was to analyse the mineralization pattern of enamel and dentin in patients affected by X-linked hypophosphatemic rickets (XLHR) using micro-CT (µCT), and to associate enamel and dentin mineralization in primary and permanent teeth with tooth position, gender and the presence/absence of this disease. METHODS: 19 teeth were collected from 5 individuals from the same family, 1 non-affected by XLHR and 4 affected by XLHR. Gender, age, tooth position (anterior/posterior) and tooth type (deciduous/permanent) were recorded for each patient. Following collection, teeth were placed in 0.1% thymol solution until µCT scan. Projection images were reconstructed and analysed. A plot profile describing the greyscale distance relationship in µCT images was achieved through a line bisecting each tooth in a region with the presence of enamel and dentin. The enamel and dentin mineralization densities were measured and compared. Univariate ANOVA and post hoc Tukey tests were used for all comparisons. RESULTS: Teeth of all affected patients presented dentin with a different mineralization pattern compared with the teeth of healthy patients with dentin defects observed next to the pulp chambers. Highly significant differences were found for gray values between anterior and posterior teeth (p < 0.05), affected and non-affected (p < 0.05), as well as when position and disease status were considered (p < 0.05). CONCLUSIONS: In conclusion, the mineralization patterns of dentin differed when comparing teeth from patients with and without FHR, mainly next to pulp chambers where areas with porosity and consequently lower mineral density and dentin defects were found.

Rare bone diseases and their dental, oral, and craniofacial manifestations.

Hereditary diseases affecting the skeleton are heterogeneous in etiology and severity. Though many of these conditions are individually rare, the total number of people affected is great. These disorders often include dental-oral-craniofacial (DOC) manifestations, but the combination of the rarity and lack of in-depth reporting often limit our understanding and ability to diagnose and treat affected individuals. In this review, we focus on dental, oral, and craniofacial manifestations of rare bone diseases. Discussed are defects in 4 key physiologic processes in bone/tooth formation that serve as models for the understanding of other diseases in the skeleton and DOC complex: progenitor cell differentiation (fibrous dysplasia), extracellular matrix production (osteogenesis imperfecta), mineralization (familial tumoral calcinosis/hyperostosis hyperphosphatemia syndrome, hypophosphatemic rickets, and hypophosphatasia), and bone resorption (Gorham-Stout disease). For each condition, we highlight causative mutations (when known), etiopathology in the skeleton and DOC complex, and treatments. By understanding how these 4 foci are subverted to cause disease, we aim to improve the identification of genetic, molecular, and/or biologic causes, diagnoses, and treatment of these and other rare bone conditions that may share underlying mechanisms of disease.