De novo mutation in a male patient with Fabry disease: a case report.

[fabry disease]

Fabry disease is an X-linked inherited metabolic condition where the deficit of the α-galactosidase A enzyme , encoded by the GLA gene , leads to glycosphingolipid storage , mainly globotriaosylceramide . To date , more than 600 mutations have been identified in human GLA gene that are responsible for FD , including missense and nonsense mutations , small and large deletions . Such mutations are usually inherited , and cases of de novo onset occur rarely .In this article we report an interesting case of a 44 -year -old male patient suffering from a severe form of Fabry disease , with negative family history . The patient showed signs such as cornea verticillata , angiokeratomas , cardiac and neurological manifestations , an end-stage renal disease and he had low α-galactosidase A activity . We detected , in this subject , the mutation c .493 G > C in the third exon of the GLA gene which causes the amino acid substitution D 165 H in the protein . This mutation affects the amino acid - belonging to the group of buried residues - involved , probably , in the preservation of the protein folding . Moreover , studies of multiple sequence alignment indicate that this amino acid is highly conserved , thus strengthening the hypothesis that it is a key amino acid to the enzyme functionality .The study of the relatives of the patient showed that , surprisingly , none of the members of his family of origin had this genetic alteration , suggesting a de novo mutation . Only his 11 -year -old daughter - showing acroparaesthesias and heat intolerance with reduced enzymatic activity - had the same mutation .We suggest that a non-inherited mutation of the α-galactosidase A gene is responsible for Fabry disease in the patient who had reduced enzyme activity and classical clinical manifestations of the disease . In a family , it is rare to find only one Fabry disease affected subject with a de novo mutation . These findings emphasize the importance of early diagnosis , genetic counselling , studying the genealogical tree of the patients and starting enzyme replacement therapy to prevent irreversible vital organ damage that occurs during the course of the disease .

Diseases
Validation

Diseases presenting "early diagnosis" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

adrenomyeloneuropathy

alexander disease

allergic bronchopulmonary aspergillosis

aromatase deficiency

carcinoma of the gallbladder

cholangiocarcinoma

classical phenylketonuria

coats disease

cohen syndrome

congenital adrenal hyperplasia

congenital diaphragmatic hernia

congenital toxoplasmosis

cowden syndrome

cushing syndrome

cutaneous mastocytosis

cystinuria

dentin dysplasia

dentinogenesis imperfecta

dracunculiasis

erdheim-chester disease

erythropoietic protoporphyria

esophageal carcinoma

esophageal squamous cell carcinoma

fabry disease

familial hypocalciuric hypercalcemia

familial mediterranean fever

gm1 gangliosidosis

hirschsprung disease

holt-oram syndrome

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

inclusion body myositis

kabuki syndrome

kallmann syndrome

kindler syndrome

krabbe disease

locked-in syndrome

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

omenn syndrome

oral submucous fibrosis

papillon-lefèvre syndrome

phenylketonuria

primary effusion lymphoma

primary hyperoxaluria type 1

proteus syndrome

pyomyositis

pyruvate dehydrogenase deficiency

scrub typhus

severe combined immunodeficiency

sneddon syndrome

systemic capillary leak syndrome

thoracic outlet syndrome

triple a syndrome

typhoid

von hippel-lindau disease

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

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