Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive disorder caused by pathogenic variants in ABCC6, leading to progressive calcification of elastic fibers. Although PXE typically presents in adolescence with dermatologic or ocular manifestations, early vascular involvement, including pediatric hypertension, is increasingly recognized. We report a 3-year-old boy referred for evaluation of persistent erythrocytosis of unclear etiology. Clinical, biochemical, and hematologic assessments revealed intermittent reticulocytosis, normal oxygen saturation, and suppressed/normal erythropoietin levels. Long-term zinc supplementation initiated in infancy for suspected dermatitis enteropathica preceded the onset of erythrocytosis. At age eight, severe systemic hypertension was diagnosed together with medullary nephrocalcinosis and splenic and pancreatic calcifications. Imaging excluded renal artery stenosis. Whole-exome sequencing identified compound heterozygous pathogenic ABCC6 variants, establishing the diagnosis of PXE. Ophthalmologic examination revealed peau d'orange. Blood pressure control required combination antihypertensive therapy and was associated with partial normalization of red blood cell (RBC) parameters and a marked increase in plasma renin activity. RBC enzymatic profiling demonstrated metabolic adaptations consistent with oxidative stress. This case illustrates an unusual clinical presentation of PXE in early childhood. We propose that erythrocytosis, potentially promoted by zinc supplementation, may have contributed to early vascular stress and hypertension. Later, renal microvascular calcification and renin-angiotensin-aldosterone system activation may have contributed to the persistence of elevated RBC counts despite low erythropoietin. These observations suggest that PXE may be considered in the differential diagnosis of children with unexplained hypertension, particularly when additional systemic findings are present.
Flögelová et al. (Wed,) studied this question.