Division of Neurodegenerative Disorders, Department of Neurology, Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Neurogenetics. 2023 Jul;24(3):209-213. doi: 10.1007/s10048-023-00723-x. Epub 2023 Jun 21.
Primary familial brain calcification (PFBC; formerly Fahr's disease) and early-onset Alzheimer's disease (EOAD) may share partially overlapping pathogenic principles. Although the heterozygous loss-of-function mutation c.1523 + 1G > T in the PFBC-linked gene SLC20A2 was detected in a patient with asymmetric tremor, early-onset dementia, and brain calcifications, CSF β-amyloid parameters and FBB-PET suggested cortical β-amyloid pathology. Genetic re-analysis of exome sequences revealed the probably pathogenic missense mutation c.235G > A/p.A79T in PSEN1. The SLC20A2 mutation segregated with mild calcifications in two children younger than 30 years. We thus describe the stochastically extremely unlikely co-morbidity of genetic PFBC and genetic EOAD. The clinical syndromes pointed to additive rather than synergistic effects of the two mutations. MRI data revealed the formation of PFBC calcifications decades before the probable onset of the disease. Our report furthermore exemplifies the value of neuropsychology and amyloid PET for differential diagnosis.
原发性家族性脑钙化症（PFBC；以前称为 Fahr 病）和早发性阿尔茨海默病（EOAD）可能具有部分重叠的发病机制。虽然在一名患有不对称性震颤、早发性痴呆和脑钙化的患者中检测到与 PFBC 相关基因 SLC20A2 相关的杂合性功能丧失突变 c.1523 + 1G > T，但 CSF β-淀粉样蛋白参数和 FBB-PET 提示皮质 β-淀粉样蛋白病理学。外显子组序列的遗传重新分析显示 PSEN1 中可能存在致病性错义突变 c.235G > A/p.A79T。SLC20A2 突变在两名年龄小于 30 岁的儿童中与轻度钙化分离。因此，我们描述了遗传 PFBC 和遗传 EOAD 随机极不可能共存的情况。临床综合征表明两种突变的作用是相加而非协同的。MRI 数据显示 PFBC 钙化在疾病可能发生前几十年就已经形成。我们的报告进一步说明了神经心理学和淀粉样 PET 在鉴别诊断中的价值。
