Diagnostic Challenges of Wilson Disease in Early Childhood

Year 2020, Volume: 18 Issue: 1, 41 - 52, 15.04.2020

Fatma Demirbaş , Ayça Efendioğlu Ağayev Gönül Çaltepe Ayhan Gazi Kalaycı

Abstract

INTRODUCTION: Wilson's Disease (WD) is an autosomal recessive inherited copper metabolism disorder caused by mutations in the ATP7B gene. The aim of this study was to retrospectively evaluate the patients diagnosed prior to the age of five.

MATERIALS and METHODS: Between January 2005 and December 2018, the clinical and laboratory characteristics, treatment and prognostic features of 64 WD patients, 13 of whom were ≤ 5 years old, were analyzed retrospectively.

RESULTS: Of the 64 patients in this study, 33 were male and the mean age at the time of diagnosis was 9.38 ± 3.37 years (3yr 5mo-16yr 3mo). Thirteen (20.3%) of these patients were ≤ 5 years of age (7 girls, 4.1 ± 0.6 years).
Of patients ≤ 5 years of age 38.4% presented with hepatomegaly, 53.8% with similar family history, 76.9% with elevated AST and ALT levels, 76.9% with low ceruloplasmin level, 53.8% with increased urinary copper excretion, and 50% with an increased liver copper quantification. When patients ≤ 5 years of age compared with < 5 years of age patients at the time of admission, there was a statistically significant increment on AST levels but decrement in the levels of total bilirubin, direct bilirubin, and urinary copper (p=0.023, 0.009, p=0.040, p=0.011, respectively). Of patients ≤ 5 years of age (n =10) who underwent liver biopsy, mononuclear inflammatory cell infiltration (80%), macro-vesicular steatosis (50%), and parenchymal necrosis were observed in portal areas. While liver copper quantification was 405 ± 101.3 µg / gr in patients ≤ 5 years of age, that value evaluated as 615.9 ± 56,4 μg / g in patients > 5 years of age. The amount of liver copper quantification, framework distortion and bridging necrosis on liver biopsy were statistically at increased levels in patients > 5 years of age (p = 0.03, p = 0.01, p = 0.005, respectively).

RESULTS: As seen in this study, the chance of early diagnosis of patients with WD increasing steadily. In countries like Turkey where consanguineous marriages are common, it is difficult to diagnose WD with a single test and many tests should be performed jointly

CONCLUSIONS: . Early diagnosis and treatment having a great impact on prognosis.

Keywords

Copper, Early onset, Wilson disease

Erken Çocukluk Çağında Wilson Hastaların Tanısal Zorlukları

Abstract

GİRİŞ ve AMAÇ: Wilson Hastalığı (WH), ATP7B genindeki mutasyonlardan kaynaklanan otozomal resesif geçişli, bakır metabolizması bozukluğudur. Bu çalışmada beş yaşından önce tanı alan hastaların geri dönük incelemesi amaçlanmıştır.

YÖNTEM ve GEREÇLER: Ocak 2005-Aralık 2018 tarihleri arasında bölümümüzde 13’ü ≤ 5 yaş olan 64 WH’nin klinik ve laboratuar özellikleri, tedavi ve prognozları açısından retrospektif olarak analiz edildi.

BULGULAR: Çalışmamızdaki 64 hastanın 33’ü erkek ve ortalama tanı yaşı 9,38±3,37 yıl (3y5a-16,3 yıl) idi. Bu hastaların 13’ü (% 20,3) ≤5 yaş altı hastadan (7 kız, 4,1±0,6 yıl) oluşmaktaydı.
Beş yaş altı hastaların başvuru anında %38,4’inde hepatomegali, % 53,8’inde ailede benzer hikaye, %76,9’unda AST ve ALT yüksekliği %76,9’unda seruloplazmin düşüklüğü,%53,8’inde idrarda bakır atılımı, %50’sinde artmış karaciğer bakırı mevcuttu. İstattiksel olarak anlamlı düzeyde > 5 yaş hastalar ile kıyaslandığında ≤5 yaş olan hastaların başvuru anındaki AST değeri yüksek, total billubin, direk billuribin, idrar bakırı düzeyleri düşük saptandı (sırasıyla p=0,023, 0,009, p=0,040, p=0,011). Karaciğer biyopsisi yapılan ≤5 yaş hastaların (n: 10) portal alanda mononükleer iltihabi hücre infiltrasyonu (%80), makrovesiküler yağlanma (%50) ve parankim nekrozu (%50) olduğu görüldü. Karaciğer kuru bakır ağırlığı ortalaması ≤5 yaş hastaların 405 ±101,3 µg/gr iken >5 yaş hastaların 615,9±56,4µg/gr saptandı. İstattiksel olarak anlamlı düzeyde 5 yaş üstü hastalarda karaciğer kuru bakır ağırlığı, karaciğer biyopsisinde çatı bozulması ve köprüleşme nekrozu daha fazlaydı (sırasıyla p=0,03, p=0,01, p=0,005).

TARTIŞMA ve SONUÇ: Çalışmamızda da görüldüğü gibi hastaların erken dönemde tanı alma şansı gün geçtikçe artmaktadır. Akraba evliliğinin sık olduğu ülkemiz gibi ülkelerde WH tanısında tek bir testle tanı koymak zorlaşmakta birçok testin bir arada yapılması gerekmektedir. Erken tanı ve tedavi prognoz üzerinde etkilidir

Keywords

Bakır, Erken çocukluk çağı, Wilson hastalığı

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