Internal Medicine

0521779407-09 CUNY1086/Karliner 0 521 77940 7 June 4, 2007 21:13

Homocystinuria 723

Signs & Symptoms

■mental retardation (not invariable), lens dislocation (usually down-

wards), myopia, glaucoma, cataracts, retinal detachment, Marfanoid

body habitus (true arachnodactyly rare), osteoporosis, genu valgum,

scoliosis, pectus deformity, vascular occlusive disease, strokes, malar

flush, livido reticularis, mental retardation (not invariable), psychi-

atric abnormalities

■less common features: optic atrophy, failure to thrive, hypopigmen-

tation, spontaneous pneumothorax, short stature, dystonia, seizures

(20%)

tests

Laboratory

■basic blood studies:

➣routine studies normal

■basic urine studies:

➣routine studies normal

Screening

■serum amino acid analysis (increased methionine, cystine, cystine-

homocystine disulfide)

■increased serum total homocyst(e)ine

■positive urine cyanide nitroprusside test

■increased urine homocystine

Confirmatory Tests

■assay cystathionine beta-synthetase activity in cultured fibroblasts,

lymphoblasts, or hepatocytes

Other Tests

■DNA mutation analysis available in some centers

■prenatal diagnosis possible by enzyme assay (amniocytes, fetal liver

biopsy after 2nd trimester), direct DNA analysis of informative mark-

ers (chorionic villi, amniocytes), or direct DNA if mutation known

Imaging

■X-rays: skeletal abnormalities common (osteoporosis, platyspo-

ndyly, kyphoscoliosis)

■head CT/MRI: normal until appearance of cerebrovascular disease

(venous and dural sinus thrombosis)

■angiography: may reveal narrow arteries