Browsing by Author "Dorum, Sevil"
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Publication Alkaptonuria in turkey: Clinical and molecular characteristics of 66 patients(Elsevier, 2021-03-14) Kısa, Pelin Teke; Gündüz, Mehmet; Dorum, Sevil; Uzun, Özlem Ünal; Çakar, Nafiye Emel; Yıldırım, Gonca Kılıç; Erdöl, Şahin; Hışmi, Burcu Öztürk; Tuğsal, Handan Yarkan; Uçar, Ülkü; Görükmez, Özlem; Gülten, Zümrüt Arslan; Küçükçongar, Aynur; Bülbül, Selda; Sarı, İsmail; Arslan, Nur; ERDÖL, ŞAHİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Pediatrik Metabolizma ve Beslenme Anabilim Dalı,; HSF-7083-2023Alkaptonuria (AKU) is an inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase (HGD) as a result of a defect in the HGD gene. HGD enzyme deficiency results in accumulation of homogentisic acid (HGA) in the body, which in turn leads to multisystemic clinical symptoms. The present study aimed to investigate the presenting symptoms, age at diagnosis, and clinical and genetic characteristics of AKU patients followed-up in different centers in Turkey. In this cross-sectional, multicenter, descriptive study, medical records of 66 AKU patients were retrospectively evaluated. Patients? data regarding demographic, clinical and genetic characteristics were recorded. HGD database (http://hgddatabase.cvtisr.sk/) was used to identify HGD gene variants. Of the patients, 37 (56.1%) presented with isolated dark urine and 29 (43.9%) were diagnosed based on the clinical symptoms or family screening. One of these patients was on follow-up for 2 years due to Parkinsonism and was diagnosed with AKU on further analyses. Signs of ochronosis such as joint pain, low back pain and renal stones developed in childhood in 7 patients. Eight patients were diagnosed with depression via psychiatric evaluation. There were 14 (21.2%) patients operated on for ochronosis. The most frequent mutation observed in the patients was c.175delA, which was followed by c.674G > A and c.1007-2A > T mutations. Four novel mutations (c.189G > A, c.549+1G > T, c.1188+1G > A, and c.334 T > G) were identified in the patients included in the study. In addition to the known signs such as dark urine and skin pigmentation, symptoms involving different systems such as neurological findings and depression can also be encountered in AKU patients. The presence of a change in urine color needs to be questioned in patients presenting with different symptoms such as arthralgia/arthritis, renal stones or low-back pain, particularly in childhood, when skin ochronosis is not pronounced, and further examination should be performed.Item Clinical and genetic findings of Turkish hypophosphatasia cases(Galenos Yayıncılık, 2017-06-24) Sağlam, Halil; Erdöl, Şahin; Dorum, Sevil; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.; 0000-0003-0710-5422; 0000-0003-4402-9609; C-7392-2019; 35612700100; 54419947800; 41661166200Objective: Hypophosphatasia (HPP) is a rare, commonly unrecognized hereditary mineralization defect with a dramatically poor prognosis in severe cases. This study is the first to examine the detailed clinical and laboratory characteristics of patients with HPP and healthy carriers in Turkey. Methods: The study data were obtained retrospectively from the files of 10 healthy carriers and of 16 cases with HPP (12 children and 4 adults) who were followed in our center from 2012 to 2016. Results: The annual incidence of perinatal lethal hypophosphatasia (PLH) was estimated to be approximately 1 case per 435,517 live births,, which is the first report from Turkey. The clinical courses of the cases differed depending on the type of HPP. All of the seven cases (58.3% of all cases) with perinatal lethal form of HPP died. A need for respiratory support (p = 0.001), a history of pyridoxine-dependent seizures (p = 0.001), a low chest circumference measurement (p = 0.017), younger age at diagnosis (p = 0.029), a small head circumference at the time of presentation (p = 0.042), a low arm span to height ratio (p = 0.048), and a low serum alkaline phosphatase (ALP) level (p = 0.042) seemed to be predicting factors for mortality. The mean height standard deviation score of the patients and those of the healthy carriers did not differ significantly (p = 0.173). Different mutations were detected in nine of 14 cases (64.2%) in whom an ALPL gene mutation analysis could be performed, and five of these cases (35.7%) had novel mutations. The most common mutations were c746G>T (five alleles), c346G>A (three alleles), and c.140C>T (three alleles). In addition, the most frequently observed genotype in Turkish HPP cases was autosomal-dominant c.346G>A (p.A116T) mutations which were detected in three cases in two different families. Conclusion: Because of the respiratory problems, especially the lung hypoplasia, the clinical course is poor in cases with the perinatal lethal form of HPP. Some minor abnormalities such as mild short stature and osteopenia could be observed in asymptomatic heterozygote carriers. Laboratory findings were normal in these cases.