Higashi Satomi, Matsunoshita Natsuki, Otani Masako, Tokuhiro Etsuro, Nozu Kandai, Ito Shuichi
Department of Pediatrics, Yokosuka Kyosai Hospital, 1-16 Beigahama Street, Yokosuka City, Kanagawa, 238-0011, Japan.
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
BMC Nephrol. 2017 Sep 26;18(1):300. doi: 10.1186/s12882-017-0721-4.
Cystinosis is a rare autosomal recessive lysosomal disorder characterized by the accumulation of cystine in lysosomes. Cystinosis is much rarer in Asian than Caucasian populations. There are only 14 patients have with cystinosis alive in Japan. Most cystinosis is the nephropathic infantile form, as indicated by its apparent and severe clinical manifestations, including renal and ocular symptoms. Patients with the nephropathic juvenile form account for 5% of those with cystinosis. Their diagnosis is frequently delayed and difficult because of slower progression to end-stage renal disease and fewer cystine crystals in the cornea. Molecular analysis and a cysteine-binding protein assay should be performed when patients with proximal tubulopathy of an unknown origin are encountered.
A 12-year-old boy had been suffering from Fanconi syndrome since he was 3 years old. He was only recently diagnosed despite repeated ophthalmological examinations. Corneal cystine crystals were found when he was 12 years old, and he was diagnosed with cystinosis by high free cystine content in granulocytes (6.36 nmol half-cystine/mg protein, normal: <0.15). Analysis of the CTNS gene showed two novel heterozygous single nucleotide substitutions of c.329G > C and c.329 + 2 T > C. Both were splicing site variants causing exon 6 skipping proven by transcript analysis, although the functional prediction site showed c.329G > C, p.(Gly110Ala) as a benign missense substitution. The patient's estimated glomerular filtration rate was 66.8 mL/min/1.73 m. He was immediately treated with cysteamine after diagnosis.
Even if no ophthalmological abnormalities are present, nephropathic juvenile cystinosis should be suspected in children with Fanconi syndrome. Transcript analysis was useful to detect pathogenic splicing variants in this patient.
胱氨酸病是一种罕见的常染色体隐性溶酶体疾病，其特征是胱氨酸在溶酶体中蓄积。胱氨酸病在亚洲人群中比白种人群中更为罕见。在日本，仅有14例存活的胱氨酸病患者。大多数胱氨酸病为肾病型婴儿型，其明显且严重的临床表现包括肾脏和眼部症状。肾病型青少年型患者占胱氨酸病患者的5%。由于其进展至终末期肾病较慢且角膜中胱氨酸晶体较少，其诊断常常延迟且困难。当遇到不明原因的近端肾小管病患者时，应进行分子分析和半胱氨酸结合蛋白检测。
一名12岁男孩自3岁起就患有范科尼综合征。尽管多次进行眼科检查，但直到最近才被诊断出来。12岁时发现角膜胱氨酸晶体，通过粒细胞中高游离胱氨酸含量（6.36 nmol半胱氨酸/毫克蛋白，正常：<0.15）诊断为胱氨酸病。CTNS基因分析显示两个新的杂合单核苷酸替换，即c.329G>C和c.329+2T>C。转录分析证实这两个都是导致外显子6跳跃的剪接位点变异，尽管功能预测位点显示c.329G>C，p.(Gly110Ala)为良性错义替换。患者的估计肾小球滤过率为66.8 mL/min/1.73m²。诊断后立即用半胱胺对其进行治疗。
即使没有眼科异常，对于患有范科尼综合征的儿童也应怀疑患有肾病型青少年胱氨酸病。转录分析有助于检测该患者的致病性剪接变异。
