Familial cerebral small vessel disease

Gene: GLA

Comment when marking as ready: Numerous variants reported in this phenotype

Created: 4 Jul 2016, 9:33 a.m.

Comment on list classification: Tier 1 gene for Cerebral Small Vessel Disorders in BRIDGE Study

Created: 4 Jul 2016, 9:29 a.m.

Green List (high evidence)

Fabry disease is an X-linked metabolic disorder caused by mutations in the GLA gene. Fabry causes both ischaemic and haemorrhagic strokes, of different subtypes - small vessel disease, large vessel disease and cardioembolic (due to Fabry-related cardiac disease). White matter hyperintensities are also common on brain imaging. Other clinical features include acroparaesthesia, pain crises in the extremities, renal failure, gastrointestinal, cardiac, respiratory and orthopaedic involvement. Patient smay have asymptomatic ocular involvement, with tortuous retinal and conjunctival vessels, corneal and lenticular opacities and whorl keratopathy on slit-lamp examination. They may also have reddish-purple angiokeratomas on the skin, first in the periumbilical area, then on the extensor surfaces and mucosal areas. Heterozygous females may not necessarily have mild symptoms. They may also have severe multisystem involvement with life-threatening manifestations. The diagnosis in males can be made by demonstrating low levels of alpha galactosidase enzyme activity in the plasma. Affected females may have normal enzyme levels and thus genetic testing is necessary to confirm a diagnosis.

Created: 23 Jun 2016, 2:21 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Fabry Disease; Cerebral Small Vessel Disease; Stroke; Ischemic Stroke; haemorrhagic stroke

Publications

• PMID: 22037950
• 17206462
• 15025684