Clinical and molecular characterization of an extended family with Fabry disease
Wattanasirichaigoon, D.; Svasti, J.; Cairns, J.R.Ketudat.; Tangnararatchakit, K.; Visudtibhan, A.; Keeratichamroen, S.; Ngiwsara, L.; Khowsathit, P.; Onkoksoong, T.; Lekskul, A.; Mongkolsiri, D.; Jariengprasert, C.; Thawil, C.; Ruencharoen, S.
Journal of the Medical Association of Thailand 89(9): 1528-1535
2006
ISSN/ISBN: 0125-2208 PMID: 17100396 Document Number: 2617
Objective: To characterize clinical manifestations, biochemical changes, mutation of alpha-Galactosidase (alpha-Gal A) gene A (GLA), and functional capability of mutant protein.Material and Method. 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 alpha-Gal A, and mutation analysis were performed Those with a mutation were further investigated by ophthalmological and audiological evaluations, electrocardiography, echocardiogram, urinalysis, and bloodtests 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.
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