Comprehensive clinical evaluation of a large Spanish family with Anderson-Fabry disease, novel GLA mutation and severe cardiac phenotype.

[fabry disease]

Fabry disease is an X-linked multisystemic lysosomal-storage condition . We describe a large family with a novel GLA mutation : p .M 187 R /g 7219 T >G .A namnesis /physical-exam , blood /urine analysis , α-Gal-A activity and /or genetic study of at -risk individuals and multidisciplinary evaluation in confirmed cases .4 males and 13 heterozygous-females displayed the mutation . Cardiac /renal /neurological disease was diagnosed at a mean age of 41 /29 /39 years in males and 51 /56 /46 years in females . Onset mean age was 20 years versus 42 years . 9 /15 had cardiomyopathy . Delta wave suggestive of accessory pathway was identified in 1 male and 2 females . 1 female had cardiac arrest (ventricular fibrillation , 61 years ). 2 females and 1 male died suddenly (63 , 64 and 57 years ). Cardiac -subscore of Mainz Severity-Score-Index was severe for males and females over 40 years . 4 /15 (26 %) developed early renal disease . 2 males needed dialysis . 1 male died at 69 years in spite of kidney-heart transplant .We describe the largest genetically confirmed Spanish family using multidisciplinary evaluation and MSSI calculation . The novel mutation p .M 187 R /g 7219 T >G is associated with a particularly malignant cardiac phenotype in males and females over 40 years . Severity was higher than that of the largest Spanish FOS -cohort . Short -PR with delta is being reported for the first time .

Diseases
Validation

Diseases presenting "cardiomyopathy" symptom

fabry disease

gm1 gangliosidosis

heparin-induced thrombocytopenia

hodgkin lymphoma, classical

inclusion body myositis

kindler syndrome

lamellar ichthyosis

oculocutaneous albinism

primary hyperoxaluria type 1

pyruvate dehydrogenase deficiency

waldenström macroglobulinemia

This symptom has already been validated