Amino Acid Disorders |
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| Disease Name | Homocystinuria |
| Alternate name(s) | Cystathionine beta-synthase deficiency |
| Acronym | CBS deficiency |
| Disease Classification | Amino Acid Disorder |
| Variants | Yes |
| Variant name | Pyridoxine-responsive type (the majority of cases are unresponsive to pyridoxine) |
| Symptom onset | Childhood |
| Symptoms | Ectopia lentis, vascular occlusive disease, seizures, malar flush, osteoporosis, possible decreased pigmentation of hair, skin and iris, skeletal abnormalities including genu valgum, pectus excavatum, pes cavus and marfanoid habitus. Some patients have failure to thrive and short stature. Mental retardation is possible. |
| Natural history without treatment | Mental retardation is common but not invariable. Vascular disease, stroke and psychiatric abnormalities. |
| Natural history with treatment | Decrease of thromboembolic accidents which may decrease incidence of sequelae including mental retardation, ectopia lentis, seizures and psychiatric abnormalities. Normal IQ is possible and typical of the pyridoxine-responsive variant. |
| Treatment | Pyridoxine supplementation, dietary restriction of methionine with supplementation of L-cysteine, betaine supplementation. Consider folate and vitamin B12 supplementation. |
| Other | N/A |
| Physical phenotype | Ectopia lentis, decreased pigmentation, malar flush, osteoporosis, skeletal abnormalities and marfanoid habitus |
| Inheritance | Autosomal recessive |
| General population incidence | 1:200,000 – 300,000 |
| Ethnic differences | Yes |
| Population | Irish, U.S New England |
| Ethnic incidence | 1:50,000 |
| Enzyme location | Lymphocytes, fibroblasts and liver |
| Enzyme Function | Degradation of homocysteine |
| Missing Enzyme | Cystathionine beta-synthase |
| Metabolite changes | Increased methionine in blood, increased homocystine in urine, increased total homocysteine in blood. |
| Gene | CBS gene |
| Gene location | 21q22.3 |
| DNA testing available | Yes |
| DNA testing detail | Numerous mutations have been detected. Most prevalent mutations are G307S and I278T. Most patients are compound heterozygotes. |
| Prenatal testing | Enzyme assay in cultured amniocytes (CVS not possible) |
| MS/MS Profile | N/A |
| OMIM Link | http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=236200 |
| Genetests Link | www.genetests.org |
| Support Group | National Coalition for PKU and Allied Disorders http://www.pku-allieddisorders.org/ Children Living with Inherited Metabolic Diseases http://www.climb.org.uk/ |
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