From variome to phenome: Pathogenesis, diagnosis and management of ectopic mineralization disorders

Table 2 Differential diagnosis of pseudoxanthoma elasticum manifestations[1,19,47,49,53-59]

Disease	Distinct differences with PXE
Beta-thalassemia (PXE phenocopy)	Severe anemia Reduced production of hemoglobin
PXE-like syndrome (AR; GGCX gene)	More severe cutaneous phenotype not restricted to flexural areas Vitamin K-dependent coagulation factor deficiency
GACI (AR; ENPP1 gene)	Onset in infancy or early childhood Arterial stenosis Early-onset severe myocardial ischemia High mortality rate in early childhood
Fibroelastolytic papulosis, Treatment with D-penicillamine	No ophthalmological or CV phenotype
Buschke-Ollendorf syndrome (AD; LEMD3 gene)	Skeletal manifestations (osteopoikilosis, stiff joints, osteosclerosis) No ophthalmological or CV phenotype No mineralization
Solar elastosis	Dermatological features (lentigines, mottled pigmentation, actinic keratoses, telangiectasias, xerotic texture) No ophthalmological or CV phenotype No mineralization
Late-onset focal dermal elastosis	Onset in 7th to 9th life decade No ophthalmological or CV phenotype
Cutis laxa	No ophthalmological or CV phenotype Histopathology: scarce and mottled elastic fibers, no mineralization
A(R)MD (age-related macular degeneration)	No AS No CV or dermatological phenotype Less unique lesions (outer retinal tabulation or Bruch’s membrane undulation)
Presumed ocular histoplasmosis	No AS No CV or dermatological phenotype

AD: Autosomal dominant; AR: Autosomal recessive; A(R)MD: Age-related macular degeneration; AS: Angioid streaks; CV: Cardiovascular; ENPP1: Ectonucleotide pyrophosphatase/phosphodiesterase 1; GACI: Generalized arterial calcification of infancy; GGCX: Gamma-glutamyl carboxylase; LEMD3: Lem domain-containing protein 3; PXE: Pseudoxanthoma elasticum.