Hasan ÖNAL, Servet Erdal ADAL, Semra GÜRSOY, Tuba KOÇKAR, Sezen Ugan ATİK

Galaktozemi tanılı olgularımızın klinik ve genetik değerlendirilmesi

Amaç: Galaktozemi, otozomal çekinik olarak kalıtılan bir karbonhidrat metabolizması bozukluğudur. Klasik galaktozemiye neden olan galaktoz-1-fosfat üridil transferaz eksikliği, en sık görülen enzim eksikliğidir. Galaktoz-1-fosfat üridil transferaz enzimi olmadığında hasta galaktoz-1-fosfatı metabolize edemez. Artmış galaktoz-1-fosfat karaciğer, böbrek, beyin, dil, lens, deri fibroblastlarında birikir ve hasara neden olur Çalışmada amaçlanan, dünya geneline göre ülkemizde daha sık görülen galaktozeminin, kendi olgularımızdaki klinik, moleküler ve genetik özelliklerinin değerlendirilmesidir. Gereç ve Yöntemler: Bu çalışmada, hastanemizde Ocak 2009 ile Ocak 2011 tarihleri arasında galaktozemi tanısı alan 14 olgunun klinik, moleküler ve genetik özellikleri geriye dönük olarak değerlendirildi. Bulgular: Olgularımızın dokuzu erkek, beşi kız idi. Yedi olguda anne ve baba arasında değişik derecelerde akrabalık saptandı. Bir olgunun kardeşi galaktozemi tanısıyla kaybedilmişti. Hastaneye yatırılış nedenleri; dokuz olguda sarılık, iki olguda hipoglisemi, iki olguda sepsis ve bir olguda transaminaz yüksekliği idi. Olguların hepsinde Beutler testi pozitif idi. Ortalama enzim etkinliği 0,36 ± 0,26µmol/mL idi. Yalnız altı olguda (%43) erken dönemde (ilk 15 gün) tanı koyulmuştu. Dört olguda katarakt vardı. On üç olguda Q188R mutasyonu, bir olguda homozigot N314D ve homozigot E340X mutasyonu saptandı. Denver II Gelişimsel Tarama Testi ile yapılan değerlendirmede üç olguda nörolojik gelişme geriliği saptanmıştı.Çıkarımlar: Olgularımızda en sık saptanan genetik bozukluk Q188R mutasyonudur. Olgularımızın sadece %43'ü erken dönemde tanı alabilmiştir. Erken tanının konulabilmesi için, gelişmiş ülkelere kıyasla ülkemizde daha sık saptanan galaktozeminin ulusal yenidoğan tarama programına alınması gerektiğini düşünmekteyiz.

Clinical, molecular, and genetic evaluation of galactosemia in Turkish children

Aim: Galactosemia is a carbohydrate metabolism disorder with autosomal recessive inheritance. The most frequent enzyme deficiency is galactose-1-phosphate-uridylytransferase, which causes classic galactosemia. When the enzyme is absent, an infant cannot metabolize galactose-1-phosphate and it cumulates in liver, kidney, brain, tongue, lens, and skin. This study aimed to evaluate the clinical and molecular characteristics of patients with galactosemia, which is observed more frequently in our country than anywhere else in the world.Material and Methods: This is a retrospective study that includes the moleculer and genetic charcteristics of 14 patient who were diagnosed as having galactosemia between January 2009 and January 2011. Results: Nine patients were male and 5 female. Consanguineous marriage was detected in the family history of 7 patients. One patient had a history of a deceased sibling with a confirmed diagnosis of galactosemia. The main reasons for admission to the hospital were jaundice in 9, hypoglycemia in 2, sepsis in 2, and elevated liver enzymes in 1 patient. The Beutler test was positive in all patients. The mean enzyme activity was 0.36±0.26 µmol/mL. Only 6 of our cases were diagnosed in the early period (first 15 days). Cataract was present in four patients. Q188R mutation was observed in 13 patients, and homozygote N314D and homozygote E340X mutations were observed in one patient. Three patients had impaired neurologic development according to the Denver Developmental Screening Test II.Conclusion: The most common genetic abnormality was Q188R mutation. Only 43% of our patients's disease could be diagnosed at an early stage. We suggest that galactosemia should be included in the national newborn screening program in order to make earlier diagnoses.

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