SNP Shot: Genomic Insights

Isolated sulfite oxidase deficiency (ISOD) is a nervous system disease. There are two main forms: a severe "classic" form that begins in newborns, and a milder, late-onset form that starts later in infancy or early childhood.

The classic form of ISOD manifests within days of birth with rapidly worsening signs of brain dysfunction (encephalopathy). Infants with classic ISOD experience difficult-to-control seizures and feeding problems. They develop stiff muscles leading to paralysis of the arms and legs (spastic quadriplegia) and episodes of severe muscle spasms that cause arching of the back (opisthotonus). Brain development is impaired, causing the head to grow slower than the body (progressive microcephaly). Facial features become increasingly abnormal as head growth slows. These features include a long, narrow face; deep-set, widely spaced eyes; elongated eye openings (palpebral fissures); puffy cheeks; a small nose; a long space between the nose and upper lip (philtrum); and thick lips.

Infants with classic ISOD show limited responsiveness to their environment, only startling easily at noises. They do not achieve motor milestones like rolling over or sitting up. Survival beyond a few months is rare. Those who do survive past infancy typically develop displacement of the eye lenses (ectopia lentis). However, due to brain damage causing behavioral blindness in classic ISOD, the ectopia lentis doesn't further impair their vision.

Late-onset ISOD typically appears between 6 and 18 months of age, often following a feverish illness. Unlike the classic form, seizures and ectopia lentis may be absent. Developmental delay is present, and previously acquired skills may be lost (developmental regression). Movement problems such as muscle tensing (dystonia), uncontrolled limb movements (choreoathetosis), and coordination difficulties (ataxia) occur. The signs and symptoms of late-onset ISOD can either progressively worsen or occur in episodes. Some individuals with this form survive into childhood or adolescence, but due to the rarity of the disorder, their life expectancy is unknown.

Inheritance:

ISOD is an autosomal recessive disorder. This means that an affected individual has mutations in both copies of the relevant gene. Each parent of an individual with ISOD carries one copy of the mutated gene, but typically does not display any signs or symptoms of the condition.