Neurodevelopmental Disorder, Mitochondrial, with Abnormal Movements and Lactic Acidosis

Background and History: 

This is an inherited disorder of brain development and one of many that results in severe neurological handicaps.  Only a few families have been reported.

Clinical Correlations: 

Newborns are small, which reflects intrauterine growth delay.  Poor feeding with swallowing difficulties are present early.  Psychomotor delays result in severe intellectual disabilities and most children do not achieve normal developmental milestones.  Muscle tone is decreased especially in the trunk and there may be general muscle weakness and wasting.  However, limb muscles are often stiff and hyperactive. Various abnormal movements such as tremors and unintentional, jerky movements are common.  Some patients have seizures.

Brain imaging reveals widespread and extensive defects.  The optic nerves connecting the eyes to the brain may be pale indicating that they cannot transmit visual signals normally which may be responsible for the nystagmus (constant to-and-fro eye movements) and misalignment of the eyes (strabismus).  Some   A circulating blood metabolite (serum lactate) is elevated in many patients.

Genetics: 

This is a complex hereditary disorder.  The primary mutation in both copies of a gene results in an abnormal product that is improperly localized to the mitochondria (energy producing organelles in cells) due to an unusual configuration of another gene found in some patients.

The clinical findings in this condition seems to follow an autosomal recessive pattern of transmission.  Parents are clinically normal but carry a single copy of the primary mutation.  When both parents are carriers each of their children inherit a 25% risk of receiving both mutated copies and are likely to develop this condition.

Diagnosis and Prognosis: 

This rare disorder is difficult to diagnose at birth but the lack of normal development soon draws attention to an underlying neurological problem.  Pediatricians and neurologists are likely collaborators in the diagnosis.  No treatment has been reported for the general condition.  No single test can be used to make the diagnosis but the presence of an elevated blood component (serum lactate) and the brain MRI findings in combination should be helpful.

Most children do not survive beyond early childhood.

Additional Information
Inheritance/Pedigree: 
Autosomal recessive