Fahr’s syndrome: a case of unwanted calcium in the brain
Fahr’s syndrome: a case of unwanted calcium in the brain
复制标题
法尔氏综合症：大脑中多余钙的情况
DOI：
10.1007/s11739-019-02119-y
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发表时间：
2019
影响因子：
4.6
通讯作者：
Rahul S Gandhi
中科院分区：
文献类型：
--
作者：
K. Sahu;A. Mishra;A. Lal;Rahul S Gandhi
我们怀着极大的兴趣阅读了Koratala等人最近发表在贵刊[1]上的文章。通过我们的信，我们的目的是讨论更多的事实和最新的发展方面的法尔综合征。一名70岁女性，既往有高血压和高脂血症病史，在试图从椅子上站起来时发生机械性跌倒，随后被送往急诊室。她否认有任何意识丧失、肢体不自主运动或视力模糊。除了高血压150/80 mm Hg外，她的生命体征正常。体格检查未发现任何局灶性神经功能缺损、骨折或撕裂伤。计算机断层扫描（CT）未显示任何实质出血或急性颅内病变。然而，偶然发现双侧基底节（BG）和小脑广泛钙化（图1a，B）。通过详细的病史和体格检查对患者进行重新评估。对BG钙化的可能原因进行了实验室研究，如甲状旁腺功能减退、甲状腺功能减退、重金属中毒、感染、维生素过多症和其他神经退行性疾病。由于无类似疾病家族史，上述血液检查均正常，最终诊断为特发性基底节钙化（IBGC）或法尔综合征。法尔综合征是在1930年以一位德国病理学家的名字命名的。它被认为是一种极其罕见的神经退行性疾病，患病率约低于1/1，000，000 [2]。所有基底节钙化（BGC）病例均应接受专门的神经系统检查和全面的实验室检查。为了防止任何不可逆的神经功能缺损，不要错过可治疗的病因是非常重要的。图2提到了BGC的主要类别。甲状旁腺功能减退症、甲状腺功能减退症、铅中毒、维生素D过多症、感染是少数可治疗的原因，如果及时诊断，可能会非常有益。一旦排除了已知的代谢、毒性、感染和内分泌原因，则应考虑更罕见的遗传性疾病，如神经纤维瘤病、结节性硬化症、Cockyane综合征[3，4]。在遗传性疾病中，威尔逊氏病是一个典型的可治疗疾病的例子，因此应该考虑所有肝功能紊乱和BGC的年轻患者。如果尽管进行了广泛的实验室检查，但BGC的原因仍不清楚，则应考虑特发性基底节钙化（IBGC）的可能性，也称为双侧纹状体硬齿钙质沉着症或法尔综合征[3，4]。原发性家族性脑钙化（PFBC）是一种常染色体显性遗传的家族性IBGC。法尔综合征是原发性的，与任何已知的钙、磷或铜代谢异常无关。近世纪来，没有进行与钙沉积的病理生理学相关的主要研究，然而，最近研究人员声称法尔综合征是一种动态疾病，而不仅仅是转移性钙沉积。Batla等人和拉莫斯等人的研究表明，近50%的PFBC病例存在基因突变，即SLC 20 A2（约40%病例）、PDGFB（约11%病例）、PDGFRB（约2%病例）和XPR 1（约2%病例）[5，6]。这些突变的重要性仍然是研究的主题，但到目前为止，报告的两个最重要的临床相关性是PDGFB突变与头痛，以及SLC 20 A2与帕金森病特征和中风[5-7]。* Kamal Kant Sahu drkksahu85@gmail.com
We read with great interest, the recent article by Koratala et al. published in your esteemed journal [1]. Through our letter, we aim to discuss additional facts and newer developments with regards to Fahr’s syndrome. A 70-year-old woman with past medical history of hypertension and hyperlipidemia presented to emergency room after sustaining a mechanical fall while attempting to get up from a chair. She denied any loss of consciousness, involuntary limb movements or blurring of vision. Her vitals at presentation were normal except for high blood pressure of 150/80 mm Hg. Physical examination was unremarkable for any focal neurological deficits, fractures or lacerations. Computed tomography (CT) did not reveal any parenchymal bleed or acute intracranial process. However, there was an incidental detection of extensive calcification of the bilateral basal ganglia (BG) and cerebellum (Fig. 1a, b). Re-evaluation of the patient was done with a detailed history and physical examination. Laboratory investigations for possible causes of BG calcification such as hypoparathyroidism, hypothyroidism, heavy metal poisoning, infections, hypervitaminosis and other neurodegenerative disorders were conducted. As there was no family history of similar illness and above-mentioned blood work were normal, a final diagnosis of idiopathic basal ganglia calcification (IBGC) or Fahr’s syndrome was made. Fahr’s syndrome was named after a German pathologist in 1930. It is considered as an extremely rare neurodegenerative disorder with an approximate prevalence of less than 1/1,000,000 [2]. All cases of basal ganglia calcification (BGC) should undergo a dedicated neurological examination and a comprehensive laboratory workup. To prevent any irreversible neurological deficit, it is extremely important to not miss the treatable etiologies. Figure 2 mentions about the major categories for BGC. Hypoparathyroidism, hypothyroidism, lead poisoning, hypervitaminosis D, infections are few treatable causes which if timely diagnosed could be extremely rewarding. Once known metabolic, toxic, infectious, and endocrinologic causes are ruled out, the rarer genetic disorders such as neurofibromatosis, tuberous sclerosis, Cockyane syndrome should be considered [3, 4]. Amongst the genetic disorders, Wilson’s disease is a classical example of treatable condition and hence should be considered in all young patients with deranged liver functions and BGC. If despite extensive laboratory workup, the cause for BGC remains unclear, then the possibility of idiopathic basal ganglia calcification (IBGC), also known as bilateral striopallidodentate calcinosis, or Fahr’s syndrome should be considered [3, 4]. Primary familial brain calcification (PFBC) is a familial form of IBGC which runs in an autosomal dominant fashion. Fahr’s syndrome is idiopathic in origin and has no association with any known calcium, phosphorus or copper metabolism abnormalities. For almost a century, no major studies pertinent to pathophysiology of calcium deposition were done, however, recently researchers have claimed Fahr’s syndrome to be a dynamic disease rather than just a metastatic calcium deposition. Studies by Batla et al. and Ramos et al. showed genetic mutations in almost 50% cases of PFBC namely SLC20A2 ( ~ 40% cases), PDGFB ( ~ 11% cases), PDGFRB ( ~ 2% cases), and XPR1 ( ~ 2% cases) [5, 6]. Importance of these mutations are still a topic of research but till now, the two most important clinical associations reported are PDGFB mutations with headache, and SLC20A2 with parkinsonian features and stroke [5–7]. * Kamal Kant Sahu drkksahu85@gmail.com