Early signs of vascular disease in homocystinuria: A noninvasive study by ultrasound methods in eight families with cystathionine-β-synthase deficiency

Abstract

Fourteen patients (six males, eight females; mean age, 20 years) with homocystinuria due to homozygous cystathionine-β-synthase (CBS) deficiency, underwent a vascular examination. Fourteen heterozygotes (seven males, seven females; mean age, 46 years), including 12 parents and one daughter of homozygotes (obligate heterozygotes), and one sister of a homozygote (with low enzyme activity as evaluated in vitro), were also examined. Homozygotes and heterozygotes were compared with two separate control groups of different age (mean age, 20 and 43 years, respectively). Ankle/arm systolic pressure index (by continuous-wave Doppler) was, on average, lower in homozygotes ( P < .01) and heterozygotes ( P < .05) as compared with the controls. An ankle/arm index less than 0.97 and suggesting flow-reducing arterial lesions was found in six (21%) lower limbs of homozygotes versus zero in controls ( P < .05). Echo Doppler (Duplex Scanner) abnormalities, indicating early, non-flow-reducing lesions of iliac arteries were more frequent in homozygotes (seven wall abnormalities or stenoses <15%) than in young controls ( P < .05). The corresponding figures for heterozygotes were seven wall abnormalities or stenoses (1% to 15% and one stenosis 16% to 50%) ( P < .01 v middle-aged controls). Early lesions (three wall abnormalities or stenoses <15%, three stenoses 16% to 50%) were detected in six (23%) internal carotids of heterozygotes versus three (3%) of corresponding controls ( P < .05). Technical limitations precluded the accurate detection of early lesions in the internal carotid arteries of young homozygotes and controls. No significant increase in venous abnormalities (by continuous-wave Doppler) was detected in either group of patients. Early signs of premature arterial disease were thus demonstrated in both homozygotes and heterozygotes for CBS deficiency by highly sensitive, noninvasive, ultrasound methods.