Clinical Presentation, Diagnosis, and Genetic Characteristics of Patients with Hypophosphatemic Rickets

Öz

Phosphate plays an essential role in bone mineralization. Hypophosphatemic rickets (HR) is a rare phosphate-wasting disorder that leads to rickets, which may be FGF23-dependent or independent. In this study, we aimed to evaluate the clinical features of HR patients with genotypic and phenotypic features. This study included 32 children. The suspected gene was primarily studied in cases meeting the clinical diagnosis. Variants were evaluated according to ACMG criteria. All HR patients' median ages at the onset of complaints and diagnosis were 1.5 and 5 years, respectively (p<0.001). The most common complaint is bowlegs. At the time of diagnosis, calcium was 9.70 mg/dl; phosphorus was 2.68±0.64 mg/dl; ALP was 530±245 u/l, PTH was 58.70 ng/l, tubular phosphate reabsorption was 74±17%, and TmP/GFR was 2.58±1.15. Five of 32 patients were diagnosed with McCune-Albright syndrome, and two patients were followed as HR secondary to chemotherapy. Variants of the PHEX gene were identified in 15 cases (X-linked HR). In X-linked HR patients, no statistically significant difference was found between the age of presentation and diagnosis. Diagnostic delay was observed in infantile hypercalcemia type 2 and hereditary HR with hypercalciuria patients who were followed with nephrocalcinosis from an early age. In conclusion, HR is rare, and patients with bowlegs, short stature, kidney stones, hypophosphatemia, and renal phosphate wasting should be classified as FGF-23 dependent or FGF-23 independent of initiating treatment as soon as possible. Delayed diagnosis is common in cases of nephrocalcinosis, so measurement of calcium and phosphate levels should be standard for these patients.

Anahtar Kelimeler

• Hypophosphatemic rickets
• McCune Albright Syndrome
• PHEX
• SLC34A3
• SLC34A1

Hipofosfatemik Rikets Hastalarının Klinik Başvuru, Tanı ve Genetik Özellikleri

Öz

Fosfat kemik mineralizasyonunda önemli bir rol oynar. Hipofosfatemik rikets (HR), FGF23'e bağlı veya bağımsız olabilen riketse yol açan nadir bir fosfat kaybı bozukluğudur. Bu çalışmada, hipofosfatemik rikets hastalarının klinik özelliklerini genotip ve fenotipik özellikleriyle değerlendirmeyi amaçladık. Bu çalışmaya otuz iki hasta dâhil edildi. Klinik tanıyı karşılayan olgularda öncelikle şüpheli gen çalışıldı. Varyantlar ACMG kriterlerine göre değerlendirildi. Tüm HR hastalarının şikâyetlerin başlangıcındaki ve tanıdaki medyan yaşları sırasıyla 1,5 ve 5 yıl idi (p<0,001). En sık görülen şikâyet bacak eğriliğiydi. Tanı anında kalsiyum 9,70 mg/dl; fosfor 2,68±0,64 mg/dl; ALP 530±245 u/l, PTH 58,70 ng/l, tübüler fosfat reabsorbsiyonu %74±17 ve TmP/GFR 2,58±1,15 olarak bulundu. Otuz iki hastanın beşi McCune Albright sendromu tanısı aldı ve iki hasta kemoterapiye sekonder HR olarak takip edildi. On beş vakada PHEX gen varyantları saptandı (X’e bağlı HR). X’e bağlı HR hastalarında başvuru yaşı ile tanı yaşı arasında istatistiksel olarak anlamlı bir fark bulunmadı. Erken yaştan itibaren nefrokalsinozis ile takip edilen infantil hiperkalsemi tip 2 ve hiperkalsiürik herediter hipofosfatemik raşitizm hastalarında tanı gecikmesi gözlendi. Sonuç olarak hipofosfatemik raşitizm nadir görülür ve bacak eğriliği, boy kısalığı, böbrek taşı, hipofosfatemi ve renal fosfat kaybı olan hastalar mümkün olan en kısa sürede FGF-23 bağımlı veya FGF-23 bağımsız olarak sınıflandırılmalı ve tedavi planlanmalıdır. Nefrokalsinozis olgularında tanı gecikmesi sık görüldüğünden bu hastalarda kalsiyum ve fosfat düzeylerinin ölçümü standart olmalıdır.

Anahtar Kelimeler

• Hipofosfatemik raşitizm
• McCune Albright Sendromu
• PHEX
• SLC34A3
• SLC34A1

Kaynakça

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