Clinical and Molecular Characterization of an Extended Family with Fabry Disease
Duangrurdee Wattanasirichaigoon MD*, Jisnuson Svasti PhD**, James R Ketudat Cairns PhD***, Kanchana Tangnararatchakit MD*, Anannit Visudtibhan MD*, Siriporn Keeratichamroen MSc**, Lukana Ngiwsara MSc**, Pongsakdi Khowsathit MD*, Tassanee Onkoksoong MSc***, Apatsa Lekskul MD****, Dowruang Mongkolsiri MD*****, Chanchai Jariengprasert MD******, Cheamchit Thawil MSc******, Suwimol Ruencharoen MA******
Affiliation : * Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University ** Laboratory of Biochemistry, Chulabhorn Research Institute *** Institute of Science, Suranaree University of Technology, Nakhon Ratchasima **** Department of Ophthalmology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University ***** Department of Pediatrics, Sukhothai Hospital, Sukhothai ****** Department of Otolaryngology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Objective : To characterize clinical manifestations, biochemical changes, mutation of alpha-Galactosidase
((cid:31)-Gal A) gene A (GLA), and functional capability of mutant protein.
Materials and Methods : Seventeen subjects from a family with a newly diagnosed patient with Fabry disease
were enrolled in the present study. In each individual, clinical history, physical examination, leukocyte
enzyme activity of (cid:31)-Gal A, and mutation analysis were performed. Those with a mutation were further
investigated by ophthalmological and audiological evaluations, electrocardiography, echocardiogram,
urinalysis, and blood tests to determine renal insufficiency. Expression study of the mutant protein was performed
using a Pichia pastoris expression system.
Results : Four affected males and five symptomatic female carriers were identified. Clinical manifestations
included severe neuropathic pain, acroparesthesia, hypo-/hyper-hidrosis, frequent syncope, ischemic stroke,
cardiac hypertrophy, corneal dystrophy and cart-wheel cataract, high frequency sensorineural hearing loss,
periorbital edema and subcutaneous edema over hands and interphalangeal joints. None had angiokeratoma
or renal symptoms. The authors identified a novel mutation, p.L106R, in the GLA gene. Recombinant expression
of the mutant protein gave little or no enzyme activity compared to the normal protein.
Conclusion : There were intrafamilial clinical variabilities, but consistent findings of the absence of
angiokeratoma and renal symptoms, which could represent a unique feature of this particular mutation.
Keywords : Fabry disease, GLA gene, Alpha-galactosidase A, Neuropathic pain, Renal failure, Angiokeratoma
