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

Abstract

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. (Turk Pediatri Ars 2016; 51: 204-9)

Galaktozemi̇ Ve Si̇tus İnversus Totali̇s Beraberli̇ği̇: Nadi̇r Bi̇r Olgu Sunumu

“…En sık görülen formu klasik galaktozemiye neden olan GALT eksikliğidir. Tüm dünyadaki insidansı 1/40000-1/80000'dir (1,2). Akraba evliliğinin yoğun olduğu ülkemizde ise insidansı 1/23775 olarak bildirilmektedir (1).…”

“…Tüm dünyadaki insidansı 1/40000-1/80000'dir (1,2). Akraba evliliğinin yoğun olduğu ülkemizde ise insidansı 1/23775 olarak bildirilmektedir (1). GALT eksikliğinde galaktoz-1-fosfat karaciğer, böbrek, beyin, lens, dil ve deri fibroblastlarında birikerek klinik bulgulara yol açmak-tadır.…”

“…GALT eksikliğinde galaktoz-1-fosfat karaciğer, böbrek, beyin, lens, dil ve deri fibroblastlarında birikerek klinik bulgulara yol açmak-tadır. Hastalar genellikle doğumda normal olup, beslenmeyi takiben birkaç gün içinde emmede zayıflık, kusma, ishal, hipoglisemi, kolestaz, kilo kaybı, letarji ve kanamaya eğilim gibi bulgularla getirilmektedirler (1)(2)(3). Galaktozeminin bir diğer önemli ve karakteristik bulgusu olan katarakt da zaman içinde yerleşip kalıcı görme kayıplarına neden olabilmektedir.…”

“…Tanıdaki gecikmeler kronik karaciğer hastalığına, renal tubuler asidoza ve gelişimsel geriliğe neden olmaktadır. Erken tedaviye rağmen dil gelişiminde sorunlar ve kızlarda hipergonadotropik hipogonadizm görülebilmektedir (1)(2)(3). Situs inversus totalis insidansı 1/10000 olan diğer nadir bir konjenital hastalıktır (4).…”

Pediatric cataract

“…Anterior polar cataracts are seen with PAX6 mutations whereas PITX3 mutations mainly cause posterior polar cataracts. [ 17 ] Other genes responsible for major syndromic cataracts include OCRL (Lowe syndrome),[ 18 ] GALK117q (galactosemia),[ 19 ] GLA (Fabry's disease),[ 20 ] and NHS (Nance–Horan cataract–dental syndrome). [ 21 ] Congenital cataracts with more than 40 genes and loci have been isolated.…”