Alport Sendromu Hastalarının Klinik ve Genetik Özellikleri ile Aile Bireylerinin Bulgularının Değerlendirilmesi

Abstract

Atan, R., Evaluation of clinical and genetic characteristics of Alport syndrome patients and family members, Hacettepe University Faculty of Medicine, Department of Pediatrics, Speciality Thesis in Pediatrics, Ankara, 2020. Alport syndrome is a rare, progressive, genetic glomerular disease consisting of hereditary nephritis, sensorineural hearing loss and ocular abnormalities. This study aimed to evaluate the findings of patients and family members who were followed-up with AS and to compare them with the literature. 45 patients who were followed-up with the diagnosis of AS in our hospital were included in the study. The data of the patients were evaluated retrospectively from the archive and the electronic medical records. Family history of patients, hearing, vision, kidney findings at admission and follow-up, and distribution of the findings according to heredity patterns, biopsy and genetic analysis results and recent findings of family members were examined. 26 (57.8%) of the patients had X-linked, 15 (33.3%) of them AR, 4 (8.9%) of them AD inheritance pattern. There were consanguinity among the parents of 23 patients. 39 patients had a history of kidney disease in their relatives and 8 patients were diagnosed with this reason. 10 patients (22.2%) had nephrotic and 26 patients (57.7%) had nephritic proteinuria at the first assesment. It was found that CKD developed during follow-up in 6 patients. The development age of CKD was determined as 16.8 years. The development rate of CKD (33.3%) was significantly higher in AR patients than in other forms of inheritance patterns. There is a significant relationship between progression CKD and the levels of proteinuria at the first assesment. The development rate of CKD (33.3%) was significantly higher in AR patients than in other forms of inheritance patterns. 4 patients with AD had no CKD or hearing loss. Hearing loss rate of AR patients (86.7%) was found to be statistically higher than X-linked patients (30.8%). The diagnosis of retinal pigment epithelium in two patients, anterior lenticonus in one patient and keratoconus in one patient was observed. Biopsy was performed in 30 patients. 17 patients were diagnosed with AS through kidney biopsy and 1 patient was diagnosed with AS through skin biopsy. 12 patients who were not compatible with AS, as a result of pathology, were found to be diagnosed through genetic studies. Out of 17 mothers with X-linked heterozygous, 13 (76.4%) were found to have hematuria, 9 (53%) were found to have proteinuria accompanying hematuria, and one was found to be in the CKD process. No one in the process of CKD or with a history of hearing loss was found in parents of AR patients. When the parents of four AD patients were examined, two fathers of them were found to have renal transplant and hearing loss. A total of six fathers were on follow-up after kidney transplantation. Four of them were the fathers of the X-linked heterozygous carrier girls. The other two were fathers of AD patients. Hearing loss was detected in ten siblings and eight of them were AR patients, two of them were brothers of X-linked patients. Hematuria and proteinuria were found in 21 siblings, and only hematuria was found in 3 siblings. It was learned that 2 siblings were on follow-up after kidney transplantation, 1 was on dialysis and 1 was on follow-up in the CKD process. Siblings with transplant and CKD are siblings of patients with X-linked and AR, as in our patients. As a result, AS can be presented in a wide range from hematuria and / or proteinuria to ESRD. Genetic testing is important in terms of early diagnosis and treatment since it can be diagnosed without the development of biopsy findings. Kidney disease can also be serious in female carriers with X-linked inheritance pattern. It is possible to diagnose earlier if the family has a history of kidney disease or sensorineural hearing loss. Therefore, it is important to evaluate and follow up individuals with no symptoms in this regard.