Update on Lysinuric Protein Intolerance, a Multi-faceted Disease Retrospective cohort analysis from birth to adulthood
Update on Lysinuric Protein Intolerance, a Multi-faceted Disease Retrospective cohort analysis from birth to adulthood
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DOI：
10.1186/s13023-016-0550-8
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发表时间：
2017-01-05
影响因子：
3.7
通讯作者：
de Lonlay, Pascale
中科院分区：
文献类型：
--
作者：
Mauhin, Wladimir;Habarou, Florence;de Lonlay, Pascale
背景资料：赖氨酸尿蛋白不耐受（LPI）是一种罕见的代谢性疾病，由编码阳离子氨基酸转运蛋白亚基y（+）LAT 1的SLC 7A 7基因的隐性遗传突变引起。该疾病的特征是富含蛋白质的食物不耐受伴继发性尿素循环障碍，但症状是异质性的，从浸润性肺病、肾衰竭到自身免疫并发症。这项回顾性研究的所有情况下，在内克尔医院（巴黎，法国）自1977年以来，描述了LPI在儿童和成人，以提高治疗management.Results：16例患者诊断为LPI（12男，4女，从9个家庭）进行了随访，平均为11.4年（最小最大：0.4-37.0年）。主要体征为发育不良（n = 9）、胃肠道疾病（n = 2）、血细胞减少症（n = 6）、高氨血症（n = 10）伴急性脑病（n = 4）或发育障碍（n = 3）和蛋白尿（n = 1）。随访期间，5例患者出现急性高氨血症，8例出现发育障碍。在所有患者中均观察到肾脏疾病：肾小管病变（11/11）、蛋白尿（4/16）和肾衰竭（7/16），后者在老年患者中更常见（平均发病年龄17.7岁，标准差5.33岁），具有异质性模式，包括狼疮性肾炎。我们注意到一例34岁成人心肌梗死。未能茁壮成长和噬血细胞淋巴组织细胞增多症的迹象几乎是恒定的。2例发生复发性急性胰腺炎。10例患者出现早期肺部疾病。6例死于肺泡蛋白沉积症，平均年龄4岁。这种肺部受累与死亡显著相关。在诊断时，经校正的血浆赖氨酸浓度显示，在具有严重病程和过早死亡的患者中，该值有增加的趋势（Wilcoxon p = 0.08; logrank，p = 0.17）。诊断时的年龄是总生存率的临界预测因子（logrank，p = 0.16）。结论：正如预期的那样，早期肺受累肺泡蛋白沉积症是频繁和严重的，与死亡风险增加。肾脏疾病经常发生在老年患者中。心血管和胰腺受累扩大了并发症的范围。血浆赖氨酸水平升高与蛋白质组不良之间存在临界相关性。需要加大预防力度，以优化这些患者的长期管理。
Background: Lysinuric protein intolerance (LPI) is a rare metabolic disease resulting from recessive-inherited mutations in the SLC7A7 gene encoding the cationic amino-acids transporter subunit y(+)LAT1. The disease is characterised by protein-rich food intolerance with secondary urea cycle disorder, but symptoms are heterogeneous ranging from infiltrative lung disease, kidney failure to auto-immune complications. This retrospective study of all cases treated at Necker Hospital (Paris, France) since 1977 describes LPI in both children and adults in order to improve therapeutic management.Results: Sixteen patients diagnosed with LPI (12 males, 4 females, from 9 families) were followed for a mean of 11.4 years (min-max: 0.4-37.0 years). Presenting signs were failure to thrive (n = 9), gastrointestinal disorders (n = 2), cytopenia (n = 6), hyperammonemia (n = 10) with acute encephalopathy (n = 4) or developmental disability (n = 3), and proteinuria (n = 1). During follow-up, 5 patients presented with acute hyperammonemia, and 8 presented with developmental disability. Kidney disease was observed in all patients: tubulopathy (11/11), proteinuria (4/16) and kidney failure (7/16), which was more common in older patients (mean age of onset 17.7 years, standard deviation 5.33 years), with heterogeneous patterns including a lupus nephritis. We noticed a case of myocardial infarction in a 34-year-old adult. Failure to thrive and signs of haemophagocytic-lymphohistiocytosis were almost constant. Recurrent acute pancreatitis occurred in 2 patients. Ten patients developed an early lung disease. Six died at the mean age of 4 years from pulmonary alveolar proteinosis. This pulmonary involvement was significantly associated with death. Age-adjusted plasma lysine concentrations at diagnosis showed a trend toward increased values in patients with a severe disease course and premature death (Wilcoxon p = 0.08; logrank, p = 0.17). Age at diagnosis was a borderline predictor of overall survival (logrank, p = 0.16).Conclusions: As expected, early pulmonary involvement with alveolar proteinosis is frequent and severe, being associated with an increased risk of death. Kidney disease frequently occurs in older patients. Cardiovascular and pancreatic involvement has expanded the scope of complications. A borderline association between increased levels of plasma lysine and poorer outome is suggested. Greater efforts at prevention are warranted to optimise the long-term management in these patients.