Çocuklarda Wilson Hastalığı: 21 Hastanın Analizi

Wilson hastalığı (WH), bakır metabolizmasının otozomal resesif geçişli bir bozukluğudur. Etkilenen çocuklar asemptomatik olabilir ve bu tanı koymayı zorlaştırır. Bu çalışmada WH'li hastaların klinik, laboratuvar, histopatolojik ve genetik özellikleri ve izlem sonuçlarını değerlendirmeyi amaçladık. Çalışmamıza Ocak 2010-Aralık 2020 tarihleri arasında WH tanısı konulan hastalar dahil edilmiştir. Başvuru şikayetleri, fizik muayene bulguları, akrabalık ve aile öyküsü, laboratuvar, genetik, histopatolojik değerlendirme sonuçları, tedavi ve izlem sonuçları kayıt altına alındı.18 aileden toplam 21 hasta [ortanca yaş 9,5 (1-14) yıl, 10 kız] dahil edildi. 11 (%52,4) hastada Kayser-Fleischer halkası tespit edildi. 15 hastada serum seruloplazmin (<20 mg/dl) düşüktü. 17 hastada üriner bakır atılımı >100 µg/gün idi. Bakır, 18 karaciğer biyopsisinin 9'unda rhodanin ile pozitif olarak boyandı. Karaciğer bakır içeriği tüm hastalarda >50 µg/g olup, 3 hastada 50-250 µg/g ve 15 hastada > 250 µg/g idi. 18 hastada genetik değerlendirme yapıldı ve 4 hastada ATP7B geninde heterozigot mutasyonlar, 6 hastada kombine heterozigot mutasyonlar ve 8 hastada homozigot mutasyonlar saptandı. Nörolojik bulguları olan iki hasta ve aile taraması ile tanı konulan üç asemptomatik hasta dışında, tümü karaciğer bulguları ile başvurdu. Takiplerde 2 hastada nörolojik tutulum saptandı. 16 hastada D-penisilamin ve çinko sülfat kombine tedavileri, aile taraması ile tanı konan presemptomatik bir hastaya çinko sülfat monoterapisi, nörolojik tutulumu olan dört hastada trientin ve çinko sülfat kombine tedavileri uygulandı. 15 hastada ortalama 8,3 (4-23) ayda transaminaz değerleri normale döndü. Kayser-Fleischer halkası, on bir hastanın yedisinde medyan 32,8 ayda (10-81) kayboldu. Başvuru anında fulminan karaciğer yetmezliği ile başvuran iki hastadan birine karaciğer nakli yapılırken, diğerine transplantasyona gerek kalmadan plazmaferez ve şelasyon tedavisi uygulandı. Asemptomatik transaminaz yükselmesinden akut karaciğer yetmezliğine kadar her türlü karaciğer hastalığının ayırıcı tanısında Wilson hastalığı düşünülmelidir. Erken tanı ve tedavi çok önemli olduğundan tanı konulan hastalarda aile taraması mutlaka önerilmelidir.

Anahtar Kelimeler:

Bakır, Kayser-Fleischer halkası, Seruloplazmin, Wilson hastalığı

Wilson Disease in Children: Analysis of 21 Patients

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. Affected children may be asymptomatic, makes the diagnosis more difficult. In this study, we aimed to evaluate the clinical, laboratory, histopathological and genetic characteristics, and outcomes of the patients with WD. Our study includes patients who were diagnosed with WD between January 2010 and December 2020. The presenting complaints, physical examination findings, consanguinity and family history, laboratory, genetic, histopathological evaluation results, treatment and outcomes were all recorded. A total of 21 patients from 18 families [median age 9.5 (1-14) years, 10 girls] were included. Kayser-Fleischer ring was detected in 11 (52.4%) patients. Serum ceruloplasmin (<20 mg/dl) was low in 15 patients. Urinary copper excretion was >100 µg/day in 17 patients. Copper was positively stained with rhodanine in 9 of the18 liver biopsies. Liver copper content was >50 µg/g dry weight in all patients, 50-250 µg/g in 3 patients and >250 µg/g in 15 patients. Genetic evaluation was available in 18 patients and revealed heterozygous mutations in the ATP7B gene in 4 patients, combined heterozygous mutations in 6, and homozygous mutations in 8. Except for two patients with neurological findings and three asymptomatic patients who were diagnosed by family screening, all were presented with liver findings. Neurological involvement was also detected in 2 patients during follow up. D-Penicillamine and zinc sulfate combined treatments were used in 16 patients, zinc sulfate monotherapy was given to a presymptomatic patient diagnosed with family screening, and trientine and zinc sulfate combined therapies were used in four patients with neurological involvement. Transaminase values returned to normal in a median of 8.3 (4-23) months in 15 patients. The Kayser-Fleischer ring disappeared in a median of 32.8 months (10-81) in seven out of eleven patients. While liver transplantation was performed in one of the two patients who presented with fulminant hepatic failure at admission, the other was followed up with plasmapheresis and chelation therapy without the need for transplantation. Wilson disease should be considered in the differential diagnosis of all kinds of liver diseases ranging from asymptomatic elevation of transaminases to acute liver failure. Since early diagnosis and treatment are very important, family screening should definitely be recommended in diagnosed patients.

Keywords:

Copper, Kayser-Fleischer ring, Ceruloplasmin, Wilson disease,

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