Abstract Introduction Amelogenesis imperfecta type 1G (AI1G) is a rare inherited condition caused by homozygous or compound heterozygous mutations in FAM20A. The disease was characterized by hypoplastic enamel on primary and secondary dentition, delayed or failed eruption of secondary dentition, pulp stones, gingival hyperplasia, and nephrocalcinosis. Loss-of-function mutation of FAM20A is associated with fibroblast growth factor 23 (FGF23) -mediated hypophosphataemia. Here, we present a case of AI1G presenting with hypophosphatemia. Clinical Case A 23-year-old male patient was referred to our clinic with fatigue, muscle weakness, and hypophosphatemia that was detected during an evaluation for incidentally discovered nephrocalcinosis. The patient's medical history included hypoplastic enamel, unerupted permanent teeth, and newly diagnosed hypertension. The image of the permanent teeth was shown in Figure 1. His parents were consanguineous. Family history was unremarkable. In examination, his length was 172 cm, and his weight was 65 kg. The patient had dental prostheses; otherwise, the physical examination findings were normal. Laboratory results showed creatinine, 1. 2 mg/dL (normal, 0. 7-1. 4) ; phosphorus, 1. 4 mg/dL (normal, 2. 7-4. 5) ; albumin, 4. 8 g/dL (normal, 3. 2-5. 5) ; calcium, 9. 2 mg/dL (normal, 8. 5-10. 5) ; PTH, 34 pg/mL (normal, 15-65) ; and ALP: 372 U/mL (normal, 90-220) ; 25 (OH) D level was normal, 24-hour urinary calcium, 26 mg; phosphorus, 950 mg; and creatinine, 1600 mg. Tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR) was calculated as 0. 3 mmol/L (normal, 1-1. 35) using Walton-Bijvoet nomogram. Laboratory revealed renal phosphate wasting. No glucosuria or proteinuria was detected. Bicarbonate level was normal; metabolic acidosis was not observed. Bone scintigraphy and abdominal and chest computed tomography scans were performed. No abnormalities were detected, except for bilateral nephrocalcinosis. Oral phosphate replacement and calcitriol therapy were initiated. The patient was monitored with serum calcium, phosphate, and PTH levels, renal function tests, and urinalysis, urinary ultrasonography. The doses of medication were adjusted according to plasma phosphate and PTH levels to prevent secondary hyperparathyroidism. Clinical exome sequencing identified a homozygous c. 34₃5del, p. (Leu12Alafs*67) frameshift mutation in exon 1 of the FAM20A gene. It was evaluated as a pathogenic mutation associated with AI1G (enamel-renal syndrome). After approximately 22 years of follow-up, the last laboratory results are summarized in Table 1. Conclusion Hypophosphatemia has been reported rarely in AI cases. Although the mechanism of hypophosphatemia is not clearly understood, it has been suggested that it may arise through FGF23-mediated mechanisms. Additionally, measuring plasma phosphorus levels in patients with dental findings may provide further data regarding the presence and frequency of hypophosphatemia. Figure 1: Oral view of unerupted or partially erupted permanent teeth and dental prostheses Table 1: Laboratory results at the last follow-up
Hacisahinogullari et al. (Thu,) studied this question.