目的:POLR3-HLD或4H脑白质营养不良是一种常染色体隐性遗传性疾病,其特征是骨髓增生异常,缺省症,和低促性腺激素性性腺功能减退,由POLR3A的变异体引起,POLR3B,POLR1C,或POLR3K基因。神经系统和非神经系统的临床特征和疾病严重程度各不相同。虽然以前的研究参考变量认知,这是4H的第一份报告,详细介绍了全面的神经心理学评估。方法:目前的研究提出了一个20岁的,说英语,右撇子,非西班牙裔白人女性,接受过12年的教育,患有经基因证实的4HPOLR3B相关性脑白质营养不良,无需激素替代治疗。结果:4岁时,发育迟缓,共济失调,听力损失,并且存在异常牙列。成像,内分泌学,神经系统检查显示骨髓增生异常,小脑体积减少,骨密度延迟,骨质减少,和肾上腺素的证据没有真正的青春期的迹象。20岁时的神经心理学评估显示,注意,言语记忆检索,建筑,执行者(例如处理速度,持续关注)和数学计算缺陷,以及行为失调。结论:我们对4H脑白质营养不良患者进行了首次详细的神经心理学评估。神经心理学评估显示,在影像学上观察到的认知和行为执行障碍与脊髓过少相一致。需要进一步的纵向研究来阐明与这种疾病相关的神经行为表现,以帮助护理提供者。病人,和他们的家人。
Objective: POLR3-HLD or 4H leukodystrophy is an autosomal recessive disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, and caused by variants in POLR3A, POLR3B, POLR1C, or POLR3K genes. Neurological and non-neurological clinical features and disease severity vary. While previous studies reference variable cognition, this is the first report of 4H detailing a comprehensive neuropsychological assessment. Method: The current study presents a 20-year-old, English-speaking, right-handed, non-Hispanic White female with 12 years of education with genetically confirmed 4H POLR3B-related leukodystrophy without hormonal replacement treatment. Results: At age 4, developmental delays, ataxia, hearing loss, and abnormal dentition were present. Imaging, endocrinology, and neurologic examinations revealed hypomyelination, reduced cerebellar volume, delayed bone age density, osteopenia, and evidence of adrenarche without signs of true puberty. Neuropsychological assessment at age 20 revealed global cognitive impairment with intellectual, attention, verbal memory retrieval, construction, executive (e.g. processing speed, sustained attention) and math computation deficits, along with behavioral dysregulation. Conclusion: We present the first detailed neuropsychological assessment of a patient with 4H leukodystrophy. The neuropsychological assessment revealed cognitive and behavioral dysexecutive deficits aligning with hypomyelination observed on imaging. Further longitudinal studies are needed to shed light on the neurobehavioral presentation associated with this disorder to assist care providers, patients, and their families.