Are Rare Diseases Really Rare? Gaucher Disease Screening in Patients with Hepatosplenomegaly of Unknown Origin

Öz

Background: Gaucher disease (GD) is a rare, autosomal recessive lysosomal storage disorder. Type 1 GD is the most common type, with hepatomegaly observed in approximately 80% of patients and spleno-megaly in about 90%. This study investigated the frequency of GD in patients presenting with hepato-splenomegaly of unknown etiology. This study aimed to determine the frequency of GD in patients with hepatosplenomegaly of unknown etiology. Materials and Methods: Patients who presented to the outpatient clinic between September 2016 and May 2019 and had no detectable cause for hepatomegaly and/or splenomegaly following comprehen-sive gastroenterological, hematological, and infectious disease assessments were enrolled in the study. Capillary blood samples were collected via finger prick and applied to standardized dried blood spot cards. The samples were subsequently analyzed at Archimed Laboratory (Vienna, Austria). Enzymatic activity cut-off values were defined as >2.5 µmol/L for β-glucocerebrosidase and >0.9 µmol/L for acid sphingomyelinase. Results: Of the 22 patients screened, 11 (50%) were female, with a mean age of 38.86 ± 13.78 years (range: 20–76). Among the four patients evaluated for Gaucher disease (50% female), the mean age was 43.2 ± 16.7 years (range: 20–60). Beta-glucocerebrosidase activity was below the cut-off value in six patients (26%). Four patients (18%) were found to carry pathogenic mutations; among them, two had reduced acid sphingomyelinase activity, and two had a positive family history. Based on these findings, type 1 Gaucher disease was considered in these four patients. Conclusions: Following the exclusion of common causes, screening of patients with hepatomegaly and/or splenomegaly of unknown etiology revealed low beta-glucocerebrosidase activity in approxima-tely one-fourth of the cases, and type 1 Gaucher disease was diagnosed in 4 out of 22 patients. These findings suggest that in a well-characterized cohort, Gaucher disease, although typically considered a rare disorder, may be more frequent than previously thought.

Anahtar Kelimeler

• Hepatomegaly
• Splenomegaly
• Gaucher Disease

Nadir Hastalıklar Gerçekten Nadir Mi? Nedeni Bilinmeyen Hepatosplenomegalili Hastalarda Gaucher Hastalığı Taraması

Öz

Amaç: Gaucher hastalığı (GH) nadir görülen, otozomal resesif (OR) geçişli, lizozomal depo hastalığıdır. En sık tip 1 GH görülmekte olup, yaklaşık %80’inde hepatomegali, %90’ında splenomegali saptanır. Bu çalışmada hepatosplenomegali saptanan ve nedeni bulunamayan hastalarda GH sıklığı araştırılmıştır. Materyal ve metod: Eylül 2016- Mayıs 2019 tarihleri arasında polikliniğine başvuran, gastroenteroloji, hematoloji ve enfeksiyon tetkikleri sonrası hepatomegali ve/veya splenomegalinin etiyolojik nedeni saptanamayan hastalar çalışmaya alındı. Hastalardan kuru kan testi için hazırlanmış hazır formlara, parmak ucundan bir damla kan alındı ve tetkik için Viyana (Avusturya)’da bulunan Archimed laboratuvarına gönderildi. Beta-glukoserebrosidaz için cut-off>2,5, asid-sfingomyelidaz için >0,9 mikromol/L alındı. Bulgular: Tarama yapılan 22 hastadan 11 tanesi (% 50) kadın, yaş ortalaması 38,86 ± 13,78 (yaş dağılımı 20-76) idi. GH düşünülen dört hastanın ikisi (%50 kadın), yaş ortalaması 43,2 ± 16,7 (yaş dağılımı 20-60) idi. Beta-glukoserebrosidaz düzeyi cut-off değerin altında altı hasta (%26) saptandı. Mutasyon saptanan, ikisinde asid-sfingomyelidaz düzeyi de düşük ve ikisinde aile hikayesi olan dört hastanın (%18,0), tip1 GH olduğu görüldü. Sonuç: Sık görülen hastalıklar ekarte edildikten sonra nedeni halen saptanamayan hepatomegali ve/veya splenomegalisi olan hastaların taramasında, hastaların dörtte birinde beta-glukoserebrosidaz enzim düşüklüğü saptanmış, 22 hastadan dört tanesine tip 1 GH tanısı konulmuştur. İyi araştırılmış bu hastalar-da tarama yapıldığında nadir görülen bir hastalık olarak bilinen GH’nın bu grup için nadir olmadığı göste-rilmiştir.

Anahtar Kelimeler

• Hepatomegali
• Splenomegali
• Gaucher hastalığı

Kaynakça

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