GENERALISED ARTERIAL CALCIFICATION OF INFANCY AND ADULT-ONSET CALCIFICATION OF JOINTS AND ARTERIES

GENERALISED ARTERIAL CALCIFICATION OF INFANCY: ENPP1 AND ABCC6 GENE ANALYSIS 

Generalised Arterial Calcification of Infancy (GACI) is characterised by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. GACI is often fatal within the first 6 months of life because of myocardial ischemia resulting in refractory heart failure. Survival to adulthood has been reported (Lorenz-Depiereux et al 2010 Am J Hum Genet 86, 267-272).

GACI is inherited in an autosomal recessive manner and is caused by disease-causing variants in the ENPP1 and ABCC6 genes (Nitschke et al 2012 Am J Hum Genet 90, 25-39). Disease-causing variants in the ENPP1 gene also cause Autosomal Recessive Hypophosphatemic Rickets (ARHR type 2) and disease-causing variants in both ENPP1 and ABCC6 also cause Pseudoxanthoma Elasticum.

ADULT-ONSET CALCIFICATION OF JOINTS AND ARTERIES: NT5E GENE ANALYSIS

Calcification of joints and arteries (CALJA) is characterised by adult-onset calcification of the lower extremity arteries, and hand and foot capsule joints. The age of onset can be as early as the second decade of life, usually involving intense joint pain or calcification in the hands. CALJA is inherited in an autosomal recessive manner and is caused by homozygous or compound heterozygous pathogenic variants in the NT5E gene (St Hilaire et al NEJM 364(5), 432-42).

The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.