3-methylglutaconic aciduria, type III

Symptoms of 3-methylglutaconic aciduria type 3 usually appear in childhood, by around 10 years old. Some of the symptoms may occur in early childhood, like decreased vision.

The health problems that can occur in 3-methylglutaconic aciduria type 3 are:

• Vision loss
• Other eye problems, like nystagmus (eye or eyes move around without the person's control), strabismus (improper alignment of the eyes), or gaze apraxia (hard time controlling eye movements)
• Movement problems (may be severe enough to prevent the person from getting around on their own and to need a wheelchair), like spasticity, ataxia (hard time controlling movement), and chorea (jerky movements)
• Intellectual disability - typically in the mild to moderate range.

High levels of 3-methylglutaconic acid can be seen in many other inborn errors of metabolism, which are conditions that affect the way our body processes certain substances. These include conditions that cause organic aciduria, defective phospholipid remodeling, and mitochondrial membrane disorders. Other syndromes can cause high levels of this molecule in urine, like Barth syndrome (TAZ defect) and DMCA syndrome (DNAJC19 defect).

3-methylglutaconic aciduria type 3 has complete penetrance, meaning that everyone will have some symptoms of the disease. However, 3-methylglutaconic aciduria type 3 has variable expression, meaning that not everyone with 3-methylglutaconic aciduria type 3 will have the same symptoms. Some people with 3-methylglutaconic aciduria type 3 will have severe movement problems requiring a wheelchair for getting around while others will not have any problems with movement. These symptoms can be highly variable even within the same family.

There have been reports of 2 changes in the OPA3 gene ("pGly93Ser" and "p.Gln105Glu") that cause autosomal dominant optic atrophy and cataract.

Optic atrophy is a relatively common symptom of many disorders.

Behr syndrome is the most similar condition to 3-methylglutaconic aciduria type 3. It is a childhood-onset syndrome with symptoms that include optic atrophy, movement problems, intellectual disability, and sensory loss. The best way to tell the difference between Behr syndrome and 3-methylglutaconic aciduria type 3 is to do urine testing for high levels of 3-methylglutaconic acid and 3-methylglutaric acid, which are high in 3-methylglutaconic aciduria type 3 but not in Behr syndrome.

Cerebral palsy can also look like 3-methylglutaconic aciduria type 3 because the neurologic symptoms (those having to do with the brain and movement problems) can look very similar to cerebral palsy. This is especially true if the vision loss is not noticed.