A 5-year-old boy with methionine adenosyltransferase (MAT) I/III deficiency, under treatment for the tentative diagnosis of homocystinuria, presented with mildly decreased appetite and sleepiness. MR imaging showed abnormal T1 and T2 prolongations and reduced diffusion in the cerebral white matter. Clinical symptoms and MR imaging findings improved after discontinuation of therapy. We speculate...

This appendix presents information on sources of data and methods of calculation used in OTA’s costeffectiveness analysis of strategies for newborn screening, which is presented in chapter 5. That chapter considered seven different strategies offering different combinations of tests for phenylketonuria (PKU), congenital hypothyroidism, galactosemia, maple syrup urine disease (MSUD), and homocys...

Marfan syndrome, homocystinuria, trauma, and simple ectopia lentis are the most common causes of pediatric lens subluxation. Many patients are best treated with a careful refraction of the phakic or aphakic pupillary axis. For those patients not achieving satisfactory refractive results, endocapsular lensectomy using modern automated vitreous cutting devices is relatively safe and successful. G...

A probable autosomal recessive mode of inheritance is described in a family with two affected sisters. The sisters showed the typical picture of Marfan syndrome and were of normal intelligence. Both parents and all four grandparents were personally examined and found to be normal. Homocystinuria was ruled out on repeated examinations. This family suggests genetic heterogeneity in Marfan syndrom...

BACKGROUND Vitamin B12 (cobalamin) is an essential cofactor in several metabolic pathways. Intracellular conversion of cobalamin to its two coenzymes, adenosylcobalamin in mitochondria and methylcobalamin in the cytoplasm, is necessary for the homeostasis of methylmalonic acid and homocysteine. Nine defects of intracellular cobalamin metabolism have been defined by means of somatic complementat...

Homozygotes for homocystinuria due to cystathionine synthase (CS) deficiency accumulate homocysteine and methionine in their blood and tissues. High-dose pyridoxin, folic acid, vitamin B12, or betaine are therapeutical options to lower the elevated homocysteine concentration. These compounds stimulate the transsulfuration or remethylation of homocysteine. Despite such treatment, elevated blood ...

Two mutations in the cystathionine beta-synthase (CBS) gene were found in two Japanese siblings with pyridoxine non-responsive homocystinuria who had different methionine levels in their blood during the neonatal period. Both patients were compound heterozygotes of two mutant alleles: one had an A-to-G transition at nucleotide 194 (A194 G) that caused a histidine-to-arginine substitution at pos...

Cystathionine-β-synthase (CBS) deficiency is a human genetic disease causing homocystinuria, thrombosis, mental retardation, and a suite of other devastating manifestations. Early detection coupled with dietary modification greatly reduces pathology, but the response to treatment differs with the allele of CBS. A better understanding of the relationship between allelic variants and protein func...

Missense mutant proteins, such as those produced in individuals with genetic diseases, are often misfolded and subject to processing by intracellular quality control systems. Previously, we have shown using a yeast system that enzymatic function could be restored to I278T cystathionine beta-synthase (CBS), a cause of homocystinuria, by treatments that affect the intracellular chaperone environm...