what is Spastic Paraplegia 50?

Hereditary Spastic Paraplegia 50 (SPG50 or AP4M1-associated hereditary spastic paraplegia) is a neurodegenerative disorder that generally presents with global developmental delay, moderate to severe intellectual disability, speech delays or absent speech, small head size, seizures, and progressive motor symptoms. The child usually displays hypotonia (low-muscle tone) and later develops hypertonia (high-muscle tone). The hypertonia creates spasticity starting in the lower legs and working up. Typically the spasticity leads to a walker and then eventually wheelchair reliance. Spasticity may progress to the upper extremities, leading to the partial or total loss of use of all four limbs and torso.

Dr. Darius Ebrahimi-Fakhari and the experts in SPG50 and AP-4 related diseases at Boston Children’s Hospital have an ongoing natural history study. Through this study it is evident that disease severity ranges from child to child, but that most children fall into the severely affected (i.e. severe spasticity with paralysis and severe cognitive impairment) category. A small proportion of children, considered least severe, are able to speak in short sentences, walk with an abnormal gait, and have few to no seizures early on in the disease (less than 10 years of age). However, most children in this less severe category still experience progressive decline, ultimately losing the ability to walk and becoming quadriplegic between the ages of 10 and 20 years.

SPG50 is inherited in an autosomal recessive manner meaning both parents must pass down a disease-causing mutation to result in symptoms. SPG50 is caused by mutations in the AP4M1 gene that lead to the inability to create a protein that is necessary for a proper functioning AP-4 protein complex.

SPG47 (AP4B1), SPG51 (AP4E1), and SPG52 (AP4S1) are all similar diseases that result in similar outcomes. To learn more about the AP-4 family of disorders visit our friends at Cure AP-4.