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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several hereditary disorders induce angiopathy in the intracranial cerebrovasculature and thus cause ischemic strokes. MELAS is a maternally inherited mitochondrial disorder that produces stroke-like events. Sickle cell disease, which is the result of a single base pair substitution, is a major cause of strokes in children. Homocystinuria, an autosomal recessive syndrome, produces premature atherosclerosis. Hereditary cerebroretinal vasculopathy is an autosomal dominant disorder that causes retinal and brain infarctions. Fabry disease is an x-linked disorder that can cause stroke in adults. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is an autosomal dominant syndrome that is associated with ischemic stroke and migraine-like headaches. The clinical presentation, stroke pathophysiology, and gene defects associated with these heritable disorders are reviewed.
J Stroke Cerebrovasc Dis
PMID:Mendelian and mitochondrial disorders associated with stroke. 1790 83

Fabry disease is a rare, life-threatening, and under-diagnosed disease, with distinctive ocular manifestations identifiable during a routine eye examination. The disease is caused by an inherited deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in progressive accumulation of glycosphingolipids throughout the body. Long-term clinical manifestations include renal failure, early stroke, and cardiomyopathy. Recently, enzyme-replacement treatment has become available, heightening the importance of early diagnosis so that treatment can be initiated before irreversible organ damage. Ocular manifestations of Fabry disease include cornea verticillata (whorl-like radial lines emanating from a single vortex, visible on slit-lamp examination), distinctive lenticular opacities, and vascular tortuosity of the conjunctiva and retina. A heightened awareness of Fabry disease among ocular professionals could greatly reduce diagnostic delays and thus reduce the morbidity and mortality of the disease.
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PMID:Ocular features of Fabry disease: diagnosis of a treatable life-threatening disorder. 1857 58

The association of genetic factors and cerebral infarction (CI) has long been established. A positive family history alone is a recognized risk factor for CI and vascular events in general. However, there are certain inherited conditions that further increase the risk of stroke. These conditions are generally metabolic and mitochondrial genetic defects that have variable modes of inheritance. This article reviews major inherited metabolic disorders that predispose an individual to CI. Ten main conditions will be discussed: Fabry's disease, cerebrotendinous xanthomatosis, tangier disease, familial hypercholesterolemia, homocystinuria, methylmalonic acidemia, glutaric aciduria type I, propionic acidemia, ornithine transcarbamylase deficiency and mitochondrial encephalopathy, lactic acidosis and stroke-like phenomenon.
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PMID:Inherited metabolic disorders and cerebral infarction. 1898 43

Fabry disease is a complex, multisystemic and clinically heterogeneous disease with prominent urinary excretion of globotriaosylceramide (Gb(3)), the principal substrate of the deficient enzyme, alpha-galactosidase A. Some measure of specific treatment is possible with enzyme replacement therapy, which can be applied safely and effectively to Fabry patients. Incidence estimations of Fabry disease vary widely from 1:55 000 to 1:3000 male births. The true incidence is likely to be higher than originally thought, owing to the existence of milder variants of the disease. The main complications of Fabry disease are a 100-fold increased risk of ischaemic stroke, cardiac disease, a wide variety of arrhythmias, valvular dysfunction and cardiac vascular disease, as well as progressive renal failure usually associated with significant proteinuria. These clinical manifestations are non-specific and are often mistaken for symptoms of other disorders, thus complicating the confirmation of diagnosis. Other clinical features of the disease are often absent (angiokeratoma), subtle (corneal opacities and hypohidrosis), or unaccompanied by specific physical findings (acroparaesthesias) indicating the true nature of the underlying disease. We propose the hypothesis that alpha-galactosidase A deficiency is a modifiable cardiovascular risk factor in the general population. This hypothesis may be tested by a non-invasive high-risk screening protocol for Fabry patients with ischaemic strokes and a variety of cardiac, and renal complications. These patients would benefit from diagnosis, appropriate treatment, follow-up and surveillance. Early detection of Fabry patients would also benefit affected relatives, many of whom do not have a clear diagnosis of their clinical condition.
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PMID:Proposed high-risk screening protocol for Fabry disease in patients with renal and vascular disease. 1916 44

Little is known about the effects of enzyme replacement therapy (ERT) in kidney transplant recipients with Fabry disease. Clinical characteristics of transplant recipients in the Fabry Outcome Survey (FOS) were therefore examined in patients with Fabry disease with or without ERT. Of the 837 European patients in FOS (March 2006), 34 male patients and two female patients had received kidney transplants. Mean age at transplantation was 37.6 +/- 10.9 years, mean time since transplantation was 7.7 +/- 6.4 years, median estimated glomerular filtration rate (eGFR) was 44.4 ml/min/1.73 m(2), and median proteinuria was 296 mg/24 h. Of 27 patients with baseline data, 59% had hypertension, 74% had left ventricular hypertrophy, 22% had cardiac valve disease, 30% had arrhythmia, and 22% had transient ischaemic attacks and 15% stroke. Twenty patients (74%; two female patients, 18 male patients) were receiving ERT with agalsidase alfa. At enrollment or at the start of ERT, median eGFRs were 59 and 35 ml/min/1.73 m(2) (P = 0.05) and median proteinuria levels were 240 and 420 mg/24 h (not significant) in treated and untreated patients respectively. Renal function remained stable in patients receiving ERT. In conclusion, agalsidase alfa is well tolerated in patients with Fabry disease who have undergone renal transplantation.
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PMID:Kidney transplantation in patients with Fabry disease. 1920 91

The aim of the study was to estimate the preponderance of patterns of pediatric stroke, ischemic or hemorrhagic, their etiologies and the correct diagnostic protocol for acute management. Forty-one consecutive pediatric patients (age range 5-16 years) with an acute stroke observed in acute phase during a 10-year period, were retrospectively evaluated. Twenty-three patients underwent magnetic resonance imaging (MRI), 3 cases were studied by computed tomography (CT) without MRI, and 15 underwent both CT and MRI studies. In 9 cases, intra-arterial digital subtraction angiography (IADSA) was performed after non-invasive preliminary assessment. Seventeen hemorrhagic (41%) and 24 ischemic (59%) strokes were found. Among hemorrhagic forms, 5 cases were due to arteriovenous malformation (AVM), 7 to cavernoma, and 2 to aneurysm. Among ischemic forms, 2 were due to sickle-cell disease, 1 to hyperomocysteinemia, 1 to moyamoya syndrome, 1 to pseudoxantoma elasticum, 3 to prothrombotic state, 1 to Fabry's disease, 1 concomitant with CO intoxication, 5 to venous sinus thrombosis, and 4 to cardio-embolic state. Etiology remains unknown in 8 cases (20.5%). This study shows a moderate prevalence of ischemic over hemorrhagic strokes. Moreover, personal experience suggests that MRI is always more informative than CT and in selected cases should be the first-choice examination in the acute phase.
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PMID:Radiological strategy in acute stroke in children. 1921 43

Fabry disease is a rare, X-linked inborn error of glycosphingolipid catabolism caused by a deficiency in the activity of the lysosomal enzyme, alpha-galactosidase A. In affected patients, the enzyme substrate, globotriaosylceramide (Gb3), accumulates in cells of various tissues and organs. Lysosomal accumulation of Gb3 begins in utero, and signs and symptoms of Fabry disease emerge in childhood and adolescence. The earliest presenting symptoms are typically neuropathic pain and gastrointestinal problems, which can have a substantial impact on health-related quality of life. Life-threatening major organ involvement is rare in young patients, but signs of kidney dysfunction (e.g., proteinuria), left ventricular hypertrophy, and stroke have been reported in children. There are two enzyme preparations for therapy: agalsidase alfa and beta. In two clinical trials of enzyme replacement therapy (ERT) with agalsidase alfa, including 37 children, boys demonstrated reductions in plasma Gb3 levels, and both boys and girls reported reductions in neuropathic pain and in the use of neuropathic pain medications. Heart rate variability, which is reduced in boys with Fabry disease, was statistically significantly improved with 6 months of agalsidase alfa treatment. In a single clinical study of agalsidase beta in children (n =16), skin Gb3 deposits and plasma Gb3 levels were reduced in boys. Differences exist in the administration and the safety profile of these two enzyme formulations. Follow-up of these cohorts and additional studies will be necessary to fully evaluate long-term efficacy of ERT in children with Fabry disease.
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PMID:Fabry disease in children and the effects of enzyme replacement treatment. 1924 21

Fabry disease, an X-linked disorder of glycosphingolipids that is caused by the deficiency of alpha-galactosidase A, is associated with dysfunction of many cell types and includes a systemic vasculopathy. As a result, patients have a markedly increased risk of developing small-fiber peripheral neuropathy, stroke, myriad cardiac manifestations and chronic renal disease. Virtually all complications of Fabry disease are non-specific in nature and clinically indistinguishable from similar abnormalities that occur in the context of more common disorders in the general population. Although Fabry disease was originally thought to be very rare, recent studies have found a much higher incidence of mutations of the GLA gene, suggesting that this disorder is under-diagnosed. Although the etiology of Fabry disease has been known for many years, the mechanism by which the accumulating alpha-D-galactosyl moieties cause this multi-organ disorder has only recently been studied and is yet to be completely elucidated. Specific therapy for Fabry disease has been developed in the last few years but its role in the management of the disorder is still being investigated. Fortunately, standard 'non-specific' medical and surgical therapy is effective in slowing deterioration or compensating for organ failure in patients with Fabry disease. All these aspects are discussed in detail in the present review.
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PMID:Fabry disease. 1931 41

The application of a novel photoacoustic imaging instrument based on a Fabry-Perot polymer film sensing interferometer to imaging the small animal brain is described. This approach provides a convenient backward mode sensing configuration that offers the prospect of overcoming the limitations of existing piezoelectric based detection schemes for small animal brain imaging. Noninvasive images of the vasculature in the mouse brain were obtained at different wavelengths between 590 and 889 nm, showing that the cerebral vascular anatomy can be visualized with high contrast and spatial resolution to depths up to 3.7 mm. It is considered that the instrument has a role to play in characterizing small animal models of human disease and injury processes such as stroke, epilepsy, and traumatic brain injury.
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PMID:Three-dimensional noninvasive imaging of the vasculature in the mouse brain using a high resolution photoacoustic scanner. 1934 Jan 21

We report a unique case with co-occurrence of Turner syndrome and Fabry disease (OMIM #301500). The latter is a rare X-linked lysosomal storage disease that is characterized by partial or complete deficiency of alpha-galactosidase A (GLA; EC 3.2.1.22) following mutations in the gene (GLA) localized at Xq22.1. Accumulation of metabolic intermediates can occur in many tissues and leads to severe morbidity, especially due to renal failure, cardiac involvement and stroke. It is well established that hemizygous male mutation carriers with Fabry disease are generally more severely affected than heterozygous female mutation carriers, but disabling clinical features and disease progression often occur in female Fabry patients as well. The majority of this patient's cells are of the 45,X type, making her a hemizygous GLA mutation carrier displaying a very severe Fabry disease phenotype.
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PMID:Fabry disease in a patient with Turner syndrome. 1934 33


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