Fabry disease : diagnosis of a rare disorder

Fabry disease (FD) is an X-linked inborn error of glycosphingolipid metabolism due to thedeficiency of α-galactosidase A. The progressive accumulation of globotriaosylceramide (Gb3),particularly in the vascular endothelium, leads to renal, cardiac, and cerebrovascularmanifestations and early death. Clinical manifestations include the onset of pain and paresthesiasin extremities, angiokeratoma and hypohidrosis during childhood or adolescence. Proteinuriaand lymphedema occur with increasing age. Severe renal impairment leads to hypertension anduremia. Death usually occurs due to renal failure or cardiac or cerebrovascular disease. Diseasepresentation may be subtle, and its signs and symptoms are often discounted as malingering orare mistakenly attributed to other disorders, such as rheumatic fever, neurosis, multiple sclerosis,lupus, or petechiae.We present a 46-year-old man who since adolescence has suffered from painfulacroparesthesia, disseminated skin angiokeratomas, hypohidrosis and heat intolerance. He wassubmitted to a thorough investigation with different specialists, but never reached a diagnosis.He started hemodialysis 3 years ago and at the moment is in standby for kidney transplantation.He was enrolled in a Brazilian FD screening and a reduced serum activity of α-galactosidase A(0.0027 nmol/h/mL – reference value 4-22) confirmed the diagnosis of FD.He has angiokeratoma at the bottom area, his echocardiogram demonstrated left ventricularhypertrophy and the family history is very rich, as the patient has 15 siblings. This case represents a very common story for FD patients. They usually spend most oftheir lives trying to find someone who could understand or explain their suffering. These resultsindicate that FD may be much more common among male dialysis patients than previouslyrecognized. Subsequently, FD should be considered in every patient with unexplained renaldisease, especially when cardiac or cerebral complications suggest an underlying multisystemicdisorder. Early diagnosis of FD is important because it allows family studies to identify otheraffected relatives for genetic counseling and therapeutic intervention. A doenca de Fabry (DF) e um erro inato do metabolismo dos glicoesfingolipideos devido adeficiencia da α-galactosidase A. O acumulo progressivo de globotriaosilceramida (Gb3), particularmente no endotelio vascular, leva a manifestacoes renais, cardiacas e cerebrovascularese morte precoce. As manifestacoes clinicas incluem o inicio, durante a infância ou adolescencia,de episodios de dor e parestesias nas extremidades, angioqueratomas e hipohidrose. Com aidade, podem aparecer proteinuria e linfedema. Insuficiencia renal grave leva a hipertensao euremia. O obito ocorre devido a insuficiencia renal ou doenca cardiaca ou cerebrovascular. Aapresentacao da doenca pode ser sutil, e seus sinais e sintomas sao erroneamente atribuidosa outras doencas, como febre reumatica, neurose, esclerose multipla, lupus ou petequias.Relatamos o caso de um paciente masculino com 46 anos que, desde a adolescencia,sofre de acroparestesia, angioqueratomas disseminados, hipohidrose e intolerância ao calor. Ele foi submetido a extensa investigacao com diferentes especialistas, mas nunca chegou a umdiagnostico. Iniciou hemodialise ha 3 anos e, no momento, esta na lista de espera para transplantede rim. Participou de um programa brasileiro de triagem para DF, e uma atividade reduzida de α-galactosidase A (0,0027 nmol/h/mL – valor de referencia 4-22) confirmou o diagnostico de DF.O paciente apresenta angioqueratomas na area do calcao, seu ecocardiograma demonstrahipertrofia ventricular esquerda e sua historia familiar e rica, pois ele tem 15 irmaos.Este caso representa uma historia muito comum entre pacientes com DF. Eles geralmentepassam a maior parte de suas vidas tentando encontrar alguem que compreenda ou expliqueseu sofrimento. Estes resultados indicam que a DF pode ser muito mais comum entre homensque realizam hemodialise do que antes previsto. Subsequentemente, a DF deve ser consideradaem todo paciente com doenca renal sem causa aparente, principalmente quando complicacoescardiacas ou cerebrovasculares sugerirem uma doenca multissistemica. O diagnostico precoceda DF e importante, pois permite estudo familiar para identificar parentes afetados paraaconselhamento genetico e intervencao terapeutica.