discoveries magazine

New Neuro Disorder Discovered

Montage of a woman holding a small child, a microscope and a double helix.

A rare disorder that disrupts the motor skills of infants and teenagers has been discovered thanks to a research collaboration involving a Cedars-Sinai pediatric neurologist. Dr. Tyler Mark Pierson, joined scientists from nearly 50 institutions worldwide to report on 31 children with this condition, known as HPDL deficiency.

The genetic disorder occurs in two forms. The more severe form consists of lower-extremity spasticity associated with significant cognitive delays and frequent seizures. The milder type has a later onset and produces weakness and muscle stiffness in the legs of otherwise healthy teens. Both forms stem from abnormal activity in the cerebral cortex, which is responsible for functions such as thought, muscle tone and voluntary physical action.

Dr. Pierson and his colleagues found that the study’s subjects had abnormalities in both copies of their human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) gene, which previously was not associated with any disease. Affected children inherit one mutation from each of their unaffected parents. The combined mutations decrease levels and activity of HPDL proteins, which are important for neurons’ cellular functioning.