The ubiquitously expressed iron storage protein ferritin plays a central role in 
maintaining cellular iron homeostasis. Cytosolic ferritins are composed of heavy 
(H) and light (L) subunits that co-assemble into a hollow spherical shell with 
an internal cavity where iron is stored. The ferroxidase activity of the 
ferritin H chain is critical to store iron in its Fe3+ oxidation state, while 
the L chain shows iron nucleation properties. We describe a unique case of a 
23-yr-old female patient affected by a homozygous loss of function mutation in 
the L-ferritin gene, idiopathic generalized seizures, and atypical restless leg 
syndrome (RLS). We show that L chain ferritin is undetectable in primary 
fibroblasts from the patient, and thus ferritin consists only of H chains. 
Increased iron incorporation into the FtH homopolymer leads to reduced cellular 
iron availability, diminished levels of cytosolic catalase, SOD1 protein levels, 
enhanced ROS production and higher levels of oxidized proteins. Importantly, key 
phenotypic features observed in fibroblasts are also mirrored in reprogrammed 
neurons from the patient's fibroblasts. Our results demonstrate for the first 
time the pathophysiological consequences of L-ferritin deficiency in a human and 
help to define the concept for a new disease entity hallmarked by idiopathic 
generalized seizure and atypical RLS.