Department of Pediatrics, Ege University Faculty of Medicine, Division of Pediatric Metabolism, Izmir, Turkey.
Department of Medical Genetics, Tepecik Research and Training Hospital, Izmir, Turkey.
J Pediatr Endocrinol Metab. 2022 Jun 6;35(7):913-923. doi: 10.1515/jpem-2022-0004. Print 2022 Jul 26.
Alkaptonuria is a rare autosomal recessive genetic disorder resulting from the deficiency of homogentisate 1,2 dioxygenase (HGD), the third enzyme in the tyrosine degradation pathway. Homogentisic acid produced in excess oxidizes into ochronotic pigment polymer. Accumulation of this pigment in various tissues leads to systemic disease.
Clinical, laboratory, molecular findings and treatment characteristics of 35 patients followed up in Ege University Pediatric Nutrition, and Metabolism Department with the diagnosis of alkaptonuria were evaluated retrospectively.
Twenty-four males (68.57%) and 11 females (31.42%) with a confirmed diagnosis of alkaptonuria from 32 different families were included in the study. We identified 11 different genetic variants; six of these were novel. c.1033C>T, c.676G>A, c.664G>A, c.731_734del, c.1009G>T, c.859_862delins ATAC were not previously reported in the literature. 24 (68.57%) patients only adhered to a low-protein diet in our study group. Seven (20%) patients initiated a low protein diet and NTBC therapy. Mean urinary HGA decreased by 88.7% with nitisinone. No statistical changes were detected in urinary HGA excretion with the low protein diet group.
In our study, alkaptonuria patients were diagnosed at different ages, from infancy to adulthood, and progressed with other systemic involvement in the follow-up. Since the initial period is asymptomatic, giving potentially effective treatment from an early age is under discussion. Raising disease awareness is very important in reducing disease mortality and morbidity rates.
尿黑酸尿症是一种罕见的常染色体隐性遗传疾病，由 3-对羟苯丙酮酸二加氧酶（HGD）缺乏引起，该酶是酪氨酸降解途径中的第三个酶。过量产生的对羟苯乙酸会氧化成褐黑质色素聚合物。这种色素在各种组织中的积累会导致全身性疾病。
回顾性评估了在伊兹密尔大学儿科营养和代谢科以尿黑酸尿症诊断接受随访的 35 名患者的临床、实验室、分子发现和治疗特征。
在研究中，我们纳入了 32 个不同家庭中确诊为尿黑酸尿症的 24 名男性（68.57%）和 11 名女性（31.42%）。我们发现了 11 种不同的基因突变，其中 6 种是新的。c.1033C>T、c.676G>A、c.664G>A、c.731_734del、c.1009G>T、c.859_862delins ATAC 此前并未在文献中报道。在我们的研究组中，只有 24 名（68.57%）患者仅坚持低蛋白饮食。有 7 名（20%）患者开始低蛋白饮食和尼替西农治疗。尼替西农可使尿 HGA 降低 88.7%。低蛋白饮食组尿 HGA 排泄无统计学变化。
在我们的研究中，尿黑酸尿症患者的诊断年龄从婴儿期到成年期不等，在随访中会出现其他系统受累。由于早期无症状，因此从早期开始给予潜在有效的治疗正在讨论之中。提高对疾病的认识对于降低疾病的死亡率和发病率非常重要。
