Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese exp...Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene. Methods: Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS, followed by direct sequencing of the coding exons of CTNS. Results: From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22;45.5%), and other five were compound heterozygous for this variant (15/22;68.2%). The other mutations found were p.Q128X (c.721 C>T;2/22), p.S139F (c.755 C>T;4/22) and c.18-21delGACT (p.T7FfsX7;1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.展开更多
目的探讨观察急性肺栓塞患者肌钙蛋白Ⅰ(cTnⅠ)及氨基末端脑钠肽前体(NT-proBNP)与肺动脉压力之间的关系。方法选择102例肺栓塞患者,通过超声心动图测得肺动脉收缩压值(PASP)将其分为肺动脉高压组(>30 mm Hg)54例,肺动脉压正常组(≤3...目的探讨观察急性肺栓塞患者肌钙蛋白Ⅰ(cTnⅠ)及氨基末端脑钠肽前体(NT-proBNP)与肺动脉压力之间的关系。方法选择102例肺栓塞患者,通过超声心动图测得肺动脉收缩压值(PASP)将其分为肺动脉高压组(>30 mm Hg)54例,肺动脉压正常组(≤30 mm Hg)组48例。对所有入选的患者进行cTnⅠ、NT-proBNP和血气分析检测,观察cTnⅠ、NT-ProBNP在急性肺动脉栓塞患者中的临床意义及与肺动脉高压相关性。结果急性肺栓塞患者合并肺动脉高压组的cTnⅠ水平(0.0415±0.049 ng/ml)明显高于肺动脉压正常组(0.0255±0.0211 ng/ml),差异具有统计学意义(P<0.05);急性肺栓塞患者合并肺动脉高压组的NT-proBNP水平(2 696.3±1 933.38 pg/ml)明显高于肺动脉压正常组(465.7±226.48 pg/ml),差异具有统计学意义(P<0.05)。结论急性肺栓塞患者血清cTnⅠ和NT-proBNP的水平与是否合并肺动脉高压相关,cTnⅠ和NT-proBNP可作为急性肺动脉栓塞患者病情评估的可靠指标。展开更多
文摘Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene. Methods: Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS, followed by direct sequencing of the coding exons of CTNS. Results: From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22;45.5%), and other five were compound heterozygous for this variant (15/22;68.2%). The other mutations found were p.Q128X (c.721 C>T;2/22), p.S139F (c.755 C>T;4/22) and c.18-21delGACT (p.T7FfsX7;1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.
