ABSTRACT
Objective@#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.
ABSTRACT
Mutations in CFI, mapped to 4q25 and encoding complement factor Ⅰ, are responsible for autosomal recessive atypical hemolytic uremic syndrome aHUS). Complement factor Ⅰ, a serine proteinase, plays a key role in inhibition of the amplification loop in alternative pathway. Most of mutations in the CFI gene identified in patients with aHUS are point mutations without large deletion ones. The patients with aHUS with CFI mutations, from 2 months to 32 years of age at disease onset, have a poor outcome. Approximate 70% of the patients have low levels of complement 3, and 69.6% of the cases progress to end-stage renal disease within 3 years. The risk of post-transplantation recurrences in the CFI-mutated patients is high.Therefore,detection of the CFI gene in the patients suffering from aHUS will be beneficial to making therapeutic decisions and predicting prognoses.