title: Overlap of familial Mediterranean fever and hyper-IgD syndrome in an Arabic kindred.
abstract: Hyperimmunoglobulinemia D Syndrome (HIDS) has rarely been reported in Arabs. Moreover, the simultaneous presence of mutations in MEFV and MVK segregating in the same family is exceptional. We report an Arabic girl presenting since the age of 8-years with two patterns of recurrent episodes of fever, and associated with a spectrum of clinical features suggestive of overlap between familial Mediterranean fever (FMF) and HIDS. Her 19-year old brother presented since the age of 1 year with prolonged episodes of fever and was diagnosed with HIDS at the age of 7 years based on clinical features and homozygosity for p.V377I mutation in MVK. Shorter episodes of fever and abdominal pain more consistent with FMF ensued since the age of 17 years. Genetic testing done for both patients and all other family members revealed simultaneous presence of mutations in MEFV and MVK but with a variable clinical spectrum ranging from asymptomatic to severe manifestations. Both of our patients are homozygous for p.V377I MVK mutation; the girl is a compound heterozygote for p.E148Q/p.P369S/p.R408G and p.E167D/p.F479L MEFV mutations whereas the brother is a compound heterozygote for p.E148Q/p.P369S/p.R408G and p.M680I MEFV mutations. The clinical implications of having more than one mutation in different genes of monogenic autoinflammatory diseases in the same individual are not clear but may explain atypical clinical manifestations such as the overlap features of both FMF and HIDS in this family.
authors.affiliation: Department of Pediatrics, Hamad General Hospital, Doha, Qatar, moussataha@gmail.com.
authors.forename: Taha
authors.initials: T
authors.lastname: Moussa
authors.forename: Buthaina
authors.initials: B
authors.lastname: Aladbe
authors.forename: Rowaida Z
authors.initials: RZ
authors.lastname: Taha
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Remmers
authors.forename: Hatem
authors.initials: H
authors.lastname: El-Shanti
authors.forename: Basil M
authors.initials: BM
authors.lastname: Fathalla
mesh_terms: D000328:Adult; D018912:Arabs / Q000235:genetics; D002648:Child; D003598:Cytoskeletal Proteins / Q000235:genetics; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D054078:Mevalonate Kinase Deficiency / Q000235:genetics*; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D000071198:Pyrin; D035781:Siblings; D055815:Young Adult
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase