ABCC6 gene

• Overview
• Additional information
• References

Overview

Gene (OMIM No.)	ABCC6 (#603234)
Function of gene/protein	Protein: multidrug resistance-associated protein 6 Transmembrane transporter, although identity of transported substrates not yet fully understood
Clinical phenotype (OMIM phenotype no.)	Pseudoxanthoma elasticum, PXE (#264800) Pseudoxanthoma elasticum, forme fruste (#177850) Generalized arterial calcification of infancy-2, GACI (#614473)
Inheritance	Autosomal recessive
Signs for PXE	Peau d’orange changes particularly in the temporal macula Angioid streaks Choroidal neovascularization Comet lesions
Signs for GACI	Calcification and stenosis of muscular arteries Usually fatal within first 6 months of life due to refractory heart failure
Visual function	PXE Best corrected visual acuity ≤ 20/50 in 73% of patients over age of 52 Angioid streaks present between age 15 to 25 in almost all patients Retinal hemorrhage common after age 40
Systemic features	PXE Typical onset in childhood or adolescence with cutaneous changes Characteristic small yellow papules on the neck and flexural areas which coalesce into plaques over time (cobblestone appearance of the skin); skin loosening in advanced stages Elevated risk of vascular disease (peripheral vascular disease, aneurysms, TIA/stroke, artery stenosis) Gastrointestinal/urinary tract haemorrhage (15% of cases)
Key investigations	OCT: Breaks in Bruch’s membrane can be observed along with sub-retinal haemorrhage if CNV is present Near-infrared reflectance imaging is superior to FAF and FA in detecting angiod streaks and peau d’orage changes Systemic assessment with a paediatrician and other relevant specialists
Molecular diagnosis	Skin biopsy Positive von Kossa staining showing calcification and fracture of elastic fibers in biopsy material from affected skin Next generation sequencing Targeted gene panels (retinal) Whole exome sequencing
Management	Ocular Routine eye examinations Anti-VEGF injections for choroidal neovascularization Systemic Multidisciplinary approach
Therapies under research	None at present
Further information	Medline Plus

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Additional information

• Majority of patients with heterozygous mutations present with limited manifestations of the PXE phenotype
• In rare cases, heterozygous mutations result in the full PXE phenotype in two successive generations due to pseudodominance. This specific phenotype is known as PXE, forme fruste (#177850)
• It has been suggested that GACI and PXE represent two ends of a clinical spectrum of ectopic calcification and other organ pathologies rather than two distinct disorders

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References

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