Pesaola F, Kohan R, Cismondi I A, Guelbert N, Pons P, Oller-Ramirez A M, Noher de Halac I
Hospital de Ninos de la Santisima Trinidad, Cordoba, Argentina.
Consejo Nacional de Investigaciones Cientificas y Tecnicas de Argentina (CONICET), Cordoba, Argentina.
Rev Neurol. 2019 Feb 16;68(4):155-159.
CLN8 disease is one of the thirteen recognized genetic types of neuronal ceroid lipofuscinosis, a group of neurodegenerative lysosomal storage disorders, most frequent in childhood. A putative 286 amino acids transmembrane CLN8 protein with unknown function is affected. Pathological variants in the CLN8 gene were associated with two different phenotypes: variant late-infantile in individuals from many countries worldwide, and epilepsy progressive with mental retardation, appearing in Finnish and Turkish subjects.
The girl showed psychomotor delay and dementia since birth, tonic-clonic seizures, myoclonus, ataxia with cerebellar atrophy, and early death at 12 years old. Electron microscopy of the skin showed mixed GROD, curvilinear, fingerprint cytosomes and mitochondrial hypertrophy. Two pathological DNA variants in the CLN8 gene (exon 2 c.1A>G; p.?/ exon 3 c.792C>G; p.Asn264Lys) were found confirming a compound heterozygous genotype.
This case is the Latin American index for a new congenital phenotype of the CLN8 disease. The congenital phenotype has to be added to the clinical spectrum of the CLN8 disease. The suspicion of CLN8 disease should be genetically sustained in challenging cases of a neurodegenerative syndrome with psychomotor delay since birth, speech difficulty and seizures. The course includes ataxia, cerebellar atrophy, and early death.
CLN8疾病是公认的13种神经元蜡样脂褐质沉积症遗传类型之一，这是一组神经退行性溶酶体贮积症，在儿童期最为常见。一种功能未知的推定286个氨基酸的跨膜CLN8蛋白受到影响。CLN8基因的病理变异与两种不同的表型相关：全球许多国家个体中的晚婴儿型变异，以及芬兰和土耳其受试者中出现的伴有智力迟钝的进行性癫痫。
该女孩自出生起就表现出精神运动发育迟缓、痴呆、强直阵挛性癫痫、肌阵挛、伴有小脑萎缩的共济失调，并于12岁时早逝。皮肤电子显微镜检查显示混合性颗粒状嗜锇性脂褐质沉积症（GROD）、曲线体、指纹状细胞体和线粒体肥大。在CLN8基因中发现了两个病理DNA变异（外显子2 c.1A>G；p.?/外显子3 c.792C>G；p.Asn264Lys），证实为复合杂合基因型。
该病例是CLN8疾病一种新的先天性表型的拉丁美洲首例。先天性表型应添加到CLN8疾病的临床谱中。对于自出生起就有精神运动发育迟缓、言语困难和癫痫发作的神经退行性综合征的疑难病例，应通过基因检测来支持CLN8疾病的怀疑。病程包括共济失调、小脑萎缩和早逝。
