linked hypophosphatemia (XLH) is a rare and dominant hereditary disorder linked to chromosome X, characterized by impaired renal phosphate reabsorption and vitamin D synthesis, leading to a deficiency in minor bone remodeling and teethooth abscesses 45.

We present the case of a 25-year-old Caucasian man with a family history of rickets. His brother has the same syndrome with dental and bone complication. They have inherited this disease from their mother. The patient doesn’t know if there is other member of his family who suffer from it. The patient has a brother with the same syndrome. The patient presented with gingivitis and a history of recurrent abscesses in teeth 14, 15, and 24. Clinical examination revealed several coronal restorations, porous enamel, negative sensitivity tests (performed with cotton pellets and Endo- Ice by Coltene) on all teeth, and positive percussions (performed with a mirror) on teeth 14, 15, and 24.

Periapical radiography (phosphorus number 2 plaque and X-MIND^® Unity; Acteon) and cone-beam computed tomography (X-MIND^® 3D; Acteon) (80 × 80, 150 Micron) were performed and showed periapical lesions on teeth 14, 15, 16, 24, 25, 26, 35, 36, and 46, as well as advanced endo-perio lesions on teeth 26 and 16. orthopantomogram (X-MIND^® 3D; Acteon) and bitewings (phosphorus number 2 plaque and X-MIND^® Unity; Acteon) also showed wide pulp chambers and roots canals. Figure 1, Figure 2

Rickets is a disease of growing bones observed in children and adolescents due to deficiencies in calcium, phosphate, and/or vitamin D. This disease leads to inadequate mineralization of the osteoid tissue in the growth plate, bone matrix, and teeth. The most frequent cause of rickets continues to be nutritional vitamin D deficiency, while genetic causes of rickets (hereditary rickets) are rare, accounting for approximately 13% of all cases of rickets 1.

Several rare genetic causes of rickets have been described, which can be divided into two groups. The first group consists of genetic disorders of vitamin D biosynthesis and action, such as vitamin D dependent rickets type 1A (VDDR1A), vitamin D dependent rickets type 1B (VDDR1B), vitamin D dependent rickets type 2A (VDDR2A), and vitamin D dependent rickets type 2B (VDDR2B). The second group includes genetic disorders of excessive renal phosphate loss (hereditary hypophosphatemic rickets) due to the impairment of renal tubular phosphate reabsorption as a result of FGF23-related or FGF23-independent causes 1. In this case report, we focused on hypophosphatemic rickets that affected the patient, although other forms of rickets are also discussed.

The patient suffered from a form of hypophosphatemic rickets known as X- linked dominant hypophosphatemia (XLH) syndrome, which is known to affect 1 in every 20,000 births. This syndrome affects both sexes equally in terms of disease severity because of random X-inactivation in girls 1. Typical clinical findings in children include large pulp chambers and root canals, porous enamel, dental abscesses, periapical lesions, short stature (as present in this patient), wrist enlargement, rachitic rosary, bowed legs, frontal bossing, and bone pain. Osteomalacia, bone pain, dental abscesses, and spinal canal stenosis are typical presentations in adult patients due to the absorption of calcium and phosphorus into the enamel, dentin, and bone 67.

In its native form, vitamin D is inactive (25-hydroxy vitamin D). Its activation in the liver and kidneys depends on two enzymes, namely 25- hydroxylase and 1-alpha-hydroxylase 78. In its active form, namely calcitriol (1,25-hydroxy-3 vitamin D), vitamin D enables the fixation of calcium and phosphorus into the bone and teeth through the formation of a phosphate complex, allowing for mineralization 6. Table 1

XLH is characterized by an inactivation mutation in the PHEX gene, a phosphate regulator endopeptidase X-linked homolog that codes for the protein Phex 910:

a) The expression of a transmembrane endopeptidase expressed in osteoblasts and odontoblasts is downregulated via an unknown mechanism.

b) The fibroblast growth factor, FGF23, reduces the expression of the renal transporters of phosphate (NPT2A and NPT2C) and calcidiol at high concentrations of calcium and phosphorus.

c) Proteins expressed in bone and teeth modulate mineralization, which ends when this process is completed. Osteopontin is degraded by PHEX once mineralization is complete.

The abovementioned mutation in the PHEX gene results in 1112:

a) The overexpression of FGF23, which leads to a high diminution of calcidiol and the renal transporter of phosphate.

b) An accumulation of osteopontin in the extracellular matrix of bone and teeth. These changes result in a lower rate of calcium and phosphate fixation into the bone and teeth, leading to soft bone, a minor remodeling of bone, and greater porosity in the enamel, as well as clefts in dentin. These facilitate the infiltration of bacteria in the pulp, giving rise to dental abscess, periapical lesions, and minor or slow healing of these lesions.

Patients with XLH require supplementation with high levels of vitamin D, phosphate, and calcium throughout their life to avoid bone remodeling and tooth problems 13. The patient in this case report had not taken their supplements for 3 years, did not brush their teeth well, and smoked 20 cigarettes/day, complicating the healing of lesions.

The current patient’s case highlights the intricate relationship between systemic health and dental pathology. Delayed supplementation and complex clinical presentations both posed a challenge to achieving complete healing of the patient’s lesions. Monitoring of patient progression and metabolic parameters was recommended to the patient’s endocrinologist (the evaluation of treatment utilized since 2018 for this condition) to gain insights into the impact of vitamin deficiency on healing outcomes. Burosumab, a monoclonal antibody targeting the FGF23 receptor, blocks its overexpression to normalize the concentrations of calcium, vitamin D, and phosphorus 1617.

As mentioned at the beginning of this case report, there are other forms of rickets, which are summarized in Table 2 and Table 3. These include vitamin D-dependent rickets (Table 2), which are characterized by disorders in the biosynthesis of vitamin D or its receptor activity, resulting in vitamin D deficiency (type 1A (VDDR1A) and type 1B (VDDR1B)) or resistance (type 2A (VDDR2A) and type 2B (VDDR2B)). All vitamin D dependent rickets present with similar clinical and biochemical manifestations, including findings related to hypocalcemia (irritability, fatigue, muscle cramps, and seizures) and rickets (craniotabes, delayed closure of fontanelles, frontal bossing, enlarged wrists, bowed legs, short stature, and bone pain) 1. Additionally, hypophosphatemic rickets (Table 3) can be categorized as FGF23-dependent (linked to a mutation in FGF23) or FGF23- independent (linked to a mutation in another protein involved in phosphate reabsorption in the kidneys) 1.

This case report emphasizes the importance of considering systemic factors in complex endodontic procedures. The patient’s recurrent abscesses, advanced endo- perio lesions, and compromised metabolic healing highlight the need for cautious management and long-term follow-up. This report also contributes to the understanding of the complex interplay between vitamin deficiency, wound healing, and dental health, in which long-term follow-up, including clinical and radiographic assessments and blood tests, is essential for monitoring the healing and metabolic parameters. However, despite successful treatment, compromised metabolic healing raises concerns regarding overall prognosis. This article is important for clinicians and researchers in the field of genetic disorder and dentistry to understand how a systemic disease can have dental complications.