摘要目的总结一例Farber病的临床特征、诊断、治疗及预后并进行文献复习。方法对2015年10月在北京大学第一医院确诊的1例Farber病患儿的临床表现、神经电生理、头颅影像学、病理、治疗及转归等临床资料进行总结，同时应用PCR与一代测序对ASAH1基因进行突变分析，应用Pubmed数据库以“Farber′s disease”为关键词进行检索（2001年1月1日至2016年1月1日），人类基因突变数据库（HGMD）以“ASAH1 Farber′s disease”为关键词进行检索（1996至2015年），中国知网数据库以“farber氏病”为主题词进行检索（1951至2016年）。结果患儿女，2岁2月龄，因“发现关节肿胀17个月，智力、运动发育倒退11个月，间断抽搐发作2个月”入院。临床特征为痛性关节挛缩畸形、皮下结节及中枢神经系统退行性病变，以关节症状首发。脑电图见背景节律减慢及痫样放电。视觉诱发电位显著异常。颅脑磁共振成像（ MRI）示进行性脑萎缩与脑白质发育不良。皮下结节组织病理：大量结缔组织增生伴玻璃样变，较多胆固醇结晶样改变，可见泡沫细胞的浸润。 ASAH1基因存在复合杂合突变，其中c．304＿305insA （p．T102Nfs14）和c．314T＞C （p．L105P）为新发现突变，前者遗传自母亲，后者遗传自父亲。给予抗癫痫及对症治疗，效果不佳。检索符合条件的中文文献1篇，英文文献35篇，共计26例，其中男11例、女15例；1岁以内起病者77％（20／26）；46％（12／26）来自印度，其中10例印度患儿临床资料不详，余在世界范围内散发。分析有详细资料的16例患儿，其中父母近亲结婚者4例；以关节病变、皮下结节及声音嘶哑为主要临床特征者8例，以肝脾受累为主要表现者4例；合并中枢神经系统受累5例；骨质破坏1例；进行病理检查者7例，病理提示大量脂质沉积可见泡沫细胞及法伯小体。 HGMD数据库检索基因突变共计33个，突变位置主要集中在6～10号外显子上共计45％（15／33）。结论 Farber病为一种由溶酶体神经酰胺酶缺乏导致的罕见的常染色体隐性遗传性疾病，预后差，肉芽肿组织病理检查对本病的早期诊断有重要的提示作用。

abstractsObjective To explore the clinical features , diagnosis , treatment and the prognosis of Farber disease by case report and literature review .Method The clinical information of a case with farber′s disease diagnosed in October 2015 at Peking University First Hospital was collected and analyzed , including clinical manifestation , electrophysiology , magnetic resonance imaging , pathology , treatments and prognosis.ASAH1 gene mutational analysis was conducted in the patient and her parents .By using“Farber′s disease, ASAH1” as keywords, literature was searched from Pubmed, CHKD and HGMD database from January 1951 to January 2016.Result The girl, 2 years 2 months old, was sent to our hospital in October 2015, with complains of “joint swelling for 17 months, development regress of intelligence and movement for 11 months, intermittent seizures for 2 months”.The clinical manifestation of the patient was characterized by painful and deformed joints , subcutaneous nodules , progressive hoarseness , and the progressive neurological system deterioration.Joints swelling and deformity behave as the first symptoms .A series of electroencephalogram showed slow background and spike wave .Visual evoked potential was significantly abnormal.Brain magnetic resonance imaging ( MRI) showed hypomyelination and progressive diffuse brain atrophy.Histology of subcutaneous nodule showed proliferation of the connective tissue with hyalinization , cholesterol crystal like changes , and a large number of foamy cell infiltration .Compound heterozygous mutations of ASAH1 gene, c.304_305 ins A (p.T102Nfs14) and c.314T>C (p.L105p), were found in the patient , and the former is inherited from her mother , the latter from her father .Antiepileptic treatment and other symptomatic treatments were delivered to the patient , but the effectiveness was poor .One reference from China hownet and 35 references from Pubmed have reported a total of 26 cases.Twenty out of 26 patients (77%) had the onset under 1 year of age.By region, there were 12 patients (12/26, 46%) from India, and the others around world.Among these 12 indian patients, 10 lack of complete clinical data.Among the rest 16 patients, 4 patients′parents were consanguineous;8 patients with the main clinical manifestation of painful and deformed joints , subcutaneous nodules , and hoarse cry;4 patients with hepatic failure and impaired spleen;5 patients with rapid neurological deterioration;1 patient with bone destruction;7 patients under liver and skin biopsies , pathologically showing a large number of foam cells and “Farber bodies”.There are 33 genetic mutations, and 45%(15/33) mutations are concentrated in ASAH1 exon 6-10.Conclusion Farber disease is a rare autosomal recessive disease caused by deficiency of lysosomal acid ceramidase.Histopathology of granulomatous tissue plays an important role in the early diagnosis .