ESPN 50th Annual Meeting

ESPN 2017



  Familial Mediterranean Fever (FMF) is the most common hereditary periodic fever syndrome, affecting the populations surrounding Mediterranean region. Mainly it is mostly seen in Turks, Armenians, Arabs and Sephardic Jews. It is an autoinflammatory disease, which is inherited OR with recurrent abdominal pain, peritonitis, which can be watched with arthritis and skin lesions, lasting in 6-72 hours, characterized by amyloidosis in time. Disease responsible gene locus is located on chromosome 16 and is called the short arm MEFV. Colchicine is the standard treatment to prevent attacks and amyloidosis, which is a serious complication of the disease.Fabry Disease (FD) has X linked transition and is a lysosomal storage disease characterized by progressive accumulation of glycosphingolipids in various tissues and organs, caused by the mutation in the GLA gene and alpha-galactosidase A enzyme deficiency. The enzyme activity should be checked when the disease is suspected clinically.Ten years of time between diagnosis and the onset of symptoms in these patients is due to the presence of organ damage and systemic symptoms which can be confused with systemic diseases. Therefore if there is an ethnicity with in FD patients which have these symptoms, mistakenly placed diagnosis of FMF and the FD does not mind too often. Because it can be prevented, it is important to initiate early treatment. This study was aimed to create awareness for the FD.

Material and methods:

 100 patients which are diagnosed FMF according to Tell-Hashomer criterias and have MEFV gene analysis at Celal Bayar University Hospital Pediatric Nephrology Department are included in this study. 

Gal A activity analysis

Measurement of enzyme activity in dried blood spot samples was performed via DBS method using filter paper containing DBS as a source of DNA. Blood samples were collected before dialysis in hemodialysis patients and at any time in peritoneal dialysis patients. Four drops of the blood were transferred to a filter paper, allowed to dry at room temperature, and kept at 2–4 °C until analysis. The enzyme activities were calculated in μmol/L/h or pmol/spot*20h.  Patients with values <1.2 µmol/l/h or <200 pmol/spot*20h were considered to have low α-Gal A activity.

GLA mutation on genetic analysis

In patients with low α-Gal A activity, screening of the GLA mutation was performed using DBS cards based on Sanger sequence analysis. This assay uses PCR amplification followed by Sanger DNA sequencing to detect mutations in the GLA gene that cause Fabry disease. The gene encoding GLA is found on Xq22, and spans 13kb of genomic DNA (7 exons, cDNA of 1290 bases). The GLA gene encodes a 429 amino acid protein, of which the first 31 residues form a lysosomal signal peptide. Classical phenotypes are typically caused by misssense, nonsense, severe splicing mutations and large gene defects. Variant phenotypes are typically caused by splicing defects that express residual enzyme activity. The coding sequences and flanking intronic sequences (minimum of 20 base pairs) of exons 1-7 of the GLA gene are amplified from purified genomic DNA and sequenced in the forward and reverse directions. Sequencing of a single exon is available for targeted mutation analysis. Patient sequences are compared to the reference DNA sequence (GenBank Accession: X14448, NM_000169.1)


 35% of the patients in this study were male and 65% female. Male / female ratio was 1 / 1.8 was found. The mean age of onset of symptoms is 5.89 ± 3.35. FMF diagnosed family member was found in %59 of patients. The most common symptoms of patients with initial symptoms include fever (89%) and abdominal pain (94%). Then follows arthralgia (51%) , arthritis (20%) , chest pain (30%), erysipelas (9%). When the M694V is the most common allele frequency rate of 40.5 % and respectively others are E148Q 11%, V726A 7%, M680 5.5 %, R202Q 5%, R761H 4.5% found. The most common genotypes are respectively M694V homozygotes, E148Q heterozygotes and M694V heterozygotes. The main symptoms that are common with other gastrointestinal symptoms of Fabry patients which are encountered during the course of the disease are nausea %28, diarrhea %13 and constipation %15. Incidence of neurological symptoms are headache 32%, akroparesthesis 23% and tinnitus 16%. Alpha-galactosidase A enzyme activity in 2 male patients from the study group were significantly lower but in the GLA gene analysis it wasn’t found a mutation that belong to FD.


 Sometime at first in FD patients which have FMF like symptoms are unnecessaryly treated with colchicine medication. Therefore patients which are diagnosed as FMF and do not well respond to colchicine treatment should be carefully re-examined clinically.  Because FD can be prevented, it is important to initiate early treatment