| Clinical features Autosomal recessive mutations in ISCA2 gene cause “multiple mitochondrial dysfunctions syndrome 4” characterized by leukodystrophy, optic atrophy, nystagmus, hypotonia with spasticity and neurodevelopmental regression to vegetative state. Additional symptoms may include visual impairment, loss of eye contact, cognitive disability, spasticity, hyperreflexia, speech absent, periventricular white matter abnormalities, and seizures. Newborns typically attain normal development during initial months of life. Between 3-7 months of first year, patients show a triad of diffuse white matter disease, nystagmus with optic atrophy, and neurodevelopmental regression. As the disease advances, global psychomotor regression continues with varying degree. In certain instances seizures may appear. Affected individuals end up with vegetative state that eventual leads to death during early childhood. |
Prevalence
The prevalence of the disease is not known. Twenty one affected individuals, mostly Arab, from 20 families have been reported in the literature. Ethnicity of a few patients (n=3) is not reported; one of which is presumably Italian. Remaining patients are Arab descendants from Saudi Arabia (19/22), which may suggest a higher prevalence of the disorder among Arabs.
Inheritance
“Multiple mitochondrial dysfunctions syndrome 4” is inherited in an autosomal recessive manner.