Homocystinuria

Homocystinuria is a rare congenital disorder of metabolism. 

Clinical presentation

The disease may affect one or more of the systems below ^1,2:

• eye: ectopia lentis (typically downwards and inwards)

• CNS: seizures, dystonia, developmental delay

• skeletal: scoliosis, pectus excavatum, long limbs, biconcave vertebrae

• vascular: thromboembolism, annuloaortic ectasia

Pathology

A deficiency of the enzyme cystathionine-β-synthase causes classical homocystinuria whereby the metabolism of homocysteine to methionine is affected. This is due to a mutation of the CBS gene on chromosome 21q22.3 and is inherited in an autosomal recessive fashion. Other forms of secondary homocystinuria can be seen in other rare inborn metabolism disorders (e.g. methylenetetrahydrofolate reductase deficiency) ¹. 

Markers

High levels of plasma total homocysteine and methionine are present ¹. Neonatal screening heel-prick tests typically include testing for homocystinuria.

Radiographic features

No radiographic features are specific for homocystinuria and the diagnosis is made through genetic and laboratory testing. Rarely, some associations of the disease may be visible on imaging (e.g. spontaneous pneumothorax or thromboembolism) ^1-3.

MRI

Although not specific, MRI brain may show ⁴:

• multiple cortical-subcortical infarctions in the cerebellar and cerebral hemispheres of varying ages

• diffuse white matter signal intensity abnormalities may be present secondary to demyelination

• occlusive vessel or dural sinus disease on MR angiography or venography

• lens dislocation

Treatment and prognosis

Multiple treatment options are available for classical homocystinuria, including pyridoxine, betaine, and a low-methionine diet ⁵. Mortality in homocystinuria mostly occurs from premature cardiovascular disease ¹.

Differential diagnosis

• Marfan syndrome