Frequency higher in Ireland with 1 case in 65,000 population with a high prevalence of CBS 833T-C mutation detected among newborns who carry the 844ins68 variant, which neutralizes the 833T-CV mutation.

Frequency in Denmark 1 case in 20,500 live births.

Caused by Cystathionine Beta-Synthase Deficiency

Also known as cystathionine beta synthase deficiency or CBS deficiency, is an inherited disorder of the metabolism of the amino acid methionine, often involving cystathionine beta synthase.

It is an inherited autosomal recessive trait.

Multisystemic disorder of the connective tissue, muscles, CNS, and cardiovascular system.

Characterized by an accumulation of the amino acid homocysteine in the serum and an increased excretion of homocysteine in the urine.

Infants appear to be normal and early symptoms, if any are present, are vague.

Signs and symptoms of homocystinuria that may be seen include the following:

A family history of homocystinuria

Flushed cheeks l Tall, thin resembling Marfanoid habitus

Long limbs


Knock-knees known as genu valgum

Pectus excavatum and Pectus carinatum

Mental retardation


Psychiatric disease

Eye anomalies:

Ectopia lentis-in contrast to Marfan syndrome which features upward ectopia lentis, downward dislocation is the typical finding of homocystinuria or subluxation of lens



Optic atrophy

Retinal detachment


Vascular disease

Extensive atheroma formation at a young age which affects many arteries but not the coronary arteries

Intravascular thrombosis

Increased excretion of the thiol amino acid homocysteine in urine and an increased concentration in plasma.

The source of this increased homocysteine may be cystathionine beta synthase deficiency, re-methylation defects as with cobalamin defects, methionine sythase deficiency, MTHFR, and vitamin deficiencies such as cobalamin (vitamin B12) deficiency, folate (vitamin B9) deficiency, riboflavin deficiency (vitamin B2), pyridoxal phosphate deficiency (vitamin B6)).

CBS deficiency may be diagnosed by an elevation of methionine and the presence of homocysteine.

No cure exists.

Treatment uses high doses of vitamin B6, with slightly less than 50% are responsive and need to take supplemental vitamin B6 for the rest of their lives.

For patients who do not respond a low methionine diet is required, and most will need treatment with trimethylglycine.

Folic acid supplementation and occasionally adding cysteine to the diet can be helpful, as glutathione is synthesized from cysteine.

Betaine is used to reduce concentrations of homocysteine by promoting the conversion of homocysteine back to methionine.

The formed methionine is removed by incorporation into protein, and methionine not converted into protein is converted to S-adenosyl-methionine forms homocysteine again.

Treatment includes both betaine and a diet low in methionine.

In homocystinuria the plasma methionine level usually increases above the normal range of 30 micromoles/L and the potentially toxic levels of more than 400 micromoles/L may be reached.

Low-protein food is recommended for this disorder, which requires food products low in particular methionine.

The life expectancy of patients with untreated homocystinuria is reduced.


Almost  one fourth of patients below 30 years die as a result of thrombotic complications.

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