BACKGROUND Cystinosis is a rare autosomal recessive disorder caused by intracellular cystine accumulation. Proximal tubulopathy (Fanconi syndrome) is one of the first signs, leading to end-stage renal disease between the age of 12 and 16. Other symptoms occur later and encompass endocrinopathies, distal myopathy and deterioration of the central nervous system. Treatment with cysteamine if started early can delay the progression of the disease. Little is known about the neurological impairment which occurs later. The goal of the present study was to find a possible neuroanatomical dysmorphic pattern that could help to explain the cognitive profile of cystinosis patients. We also performed a detailed review of the literature on neurocognitive complications associated with cystinosis. METHODS 17 patients (mean age = 17.6 years, [5.4-33.3]) with cystinosis were included in the study. Neuropsychological assessment was performed including intelligence (Intelligence Quotient (IQ) with Wechsler's scale), memory (Children Memory Scale and Wechsler Memory Scale), visuo-spatial (Rey's figure test) and visuo-perceptual skills assessments. Structural brain MRI (3 T) was also performed in 16 out of 17 patients, with high resolution 3D T1-weighted, 3D FLAIR and spectroscopy sequences. RESULTS Intellectual efficiency was normal in patients with cystinosis (mean Total IQ = 93). However the Perceptual Reasoning Index (mean = 87, [63-109]) was significantly lower than the Verbal Comprehension Index (mean = 100, [59-138], p = 0.003). Memory assessment showed no difference between visual and verbal memory. But the working memory was significantly impaired in comparison with the general memory skills (p = 0.003). Visuospatial skills assessment revealed copy and reproduction scores below the 50th percentile rank in more than 70% of the patients. Brain MRI showed cortical and sub-cortical cerebral atrophy, especially in the parieto-occipital region and FLAIR hypersignals in parietal, occipital and brain stem/cerebellum. Patients with atrophic brain had lower Total IQ scores compared to non-atrophic cystinosis patients. CONCLUSIONS Patients with cystinosis have a specific neuropsychological and neuroanatomical profile. We suggest performing a systematic neuropsychological assessment in such children aiming at considering adequate management.

中文翻译：

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17例胱氨酸病患者的神经心理学和神经解剖学表型。

背景技术膀胱病变是由细胞内胱氨酸积累引起的罕见的常染色体隐性遗传疾病。近端肾小管病变（Fanconi综合征）是最早的体征之一，导致12至16岁之间的终末期肾脏疾病。其他症状较晚发生，包括内分泌病变，远端肌病和中枢神经系统恶化。如果尽早开始使用半胱胺治疗可以延缓疾病的进展。关于后来发生的神经损伤知之甚少。本研究的目的是发现可能的神经解剖畸形模式，以帮助解释胱氨酸症患者的认知特征。我们还对与胱氨酸病相关的神经认知并发症的文献进行了详细回顾。方法17例患者（平均年龄= 17.6岁，[5.4-33。3]）的囊肿病被纳入研究。进行了神经心理学评估，包括智力（具有Wechsler量表的智商（IQ）），记忆（儿童记忆量表和Wechsler记忆量表），视觉空间（雷伊图测试）和视觉感知能力评估。在17例患者中的16例患者中还进行了结构性脑MRI（3 T）检查，并具有高分辨率3D T1加权，3D FLAIR和光谱序列。结果胱氨酸病患者的智力效率正常（平均智商= 93）。然而，知觉推理指数（平均值= 87，[63-109]）显着低于言语理解指数（平均值= 100，[59-138]，p = 0.003）。记忆评估显示视觉和口头记忆没有差异。但是与一般记忆技巧相比，工作记忆明显受损（p = 0.003）。视觉空间技能评估显示，超过70％的患者的复制和生殖得分低于第50个百分点。脑部MRI显示皮质和皮质下脑萎缩，尤其是在顶枕区域和顶，枕和脑干/小脑的FLAIR高信号。与非萎缩性胱氨酸病患者相比，萎缩性脑病患者的智商总得分较低。结论胱氨酸病患者具有特定的神经心理学和神经解剖学特征。我们建议对此类儿童进行系统的神经心理学评估，以考虑适当的管理。视觉空间技能评估显示，超过70％的患者的复制和生殖得分低于第50个百分点。脑部MRI显示皮质和皮质下脑萎缩，尤其是在顶枕区域和顶，枕和脑干/小脑的FLAIR高信号。与非萎缩性胱氨酸病患者相比，萎缩性脑病患者的智商总得分较低。结论胱氨酸病患者具有特定的神经心理学和神经解剖学特征。我们建议对此类儿童进行系统的神经心理学评估，以考虑适当的管理。视觉空间技能评估显示，超过70％的患者的复制和生殖得分低于第50个百分点。脑部MRI显示皮质和皮质下脑萎缩，尤其是在顶枕区域和顶，枕和脑干/小脑的FLAIR高信号。与非萎缩性胱氨酸病患者相比，萎缩性脑病患者的智商总得分较低。结论胱氨酸病患者具有特定的神经心理学和神经解剖学特征。我们建议对此类儿童进行系统的神经心理学评估，以考虑适当的管理。枕和脑干/小脑。与非萎缩性胱氨酸病患者相比，萎缩性脑病患者的智商总得分较低。结论胱氨酸病患者具有特定的神经心理学和神经解剖学特征。我们建议对此类儿童进行系统的神经心理学评估，以考虑适当的管理。枕和脑干/小脑。与非萎缩性胱氨酸病患者相比，萎缩性脑病患者的智商总得分较低。结论胱氨酸病患者具有特定的神经心理学和神经解剖学特征。我们建议对此类儿童进行系统的神经心理学评估，以考虑适当的管理。