Abstract Introduction Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an irresistible urge to move the legs, which often disrupts sleep onset and can significantly impact quality of life. Iron deficiency is a common primary cause of RLS. Huntington disease (HD) is a neurodegenerative disorder that has been reported to present with RLS. We present a patient with RLS with iron deficiency whose symptoms persisted despite iron supplementation, ultimately leading to a diagnosis of HD. Case Description A 34-year-old male with no significant medical history presents to the sleep clinic with leg discomfort and insomnia. A recent sleep study reported that he had 325 episodes of periodic limb movement, indicating a periodic limb movement index of 50.5 and a periodic limb movement arousal index of 28.4 arousals/hour. Initial laboratory evaluation was notable for a ferritin level of 17 ng/mL, for which he was started on iron supplementation and dopaminergic therapy. His iron deficiency anemia was attributed to his frequent blood donations. His RLS symptoms partially improved after normalization of ferritin levels. Family history revealed Huntington disease in his mother and aunt. Genetic testing revealed a fully penetrant and pathogenic allele with 41 CAG repeats. He was subsequently established at a tertiary Huntington clinic. His periodic limb movements remained the most disabling symptom, causing sleep disruption. Optimization of gabapentin was planned with consideration of low-dose opioids if symptoms remained refractory. Discussion RLS can be idiopathic and present independently, or it can be secondary. RLS has been associated with conditions such as iron deficiency, kidney disease, diabetes mellitus, pregnancy, and certain neurological disorders like Huntington disease. Tyrosine hydroxylase is one of the enzymes responsible for producing dopamine, requiring iron as a cofactor. For the same reason, iron deficiency leads to altered dopaminergic neurotransmission, one of the main pathophysiological mechanisms in RLS. Dopaminergic dysfunction also occurs in Huntington disease. However, dysfunction of the basal ganglia and striatal pathways is what leads to dopaminergic dysfunction in HD. A high suspicion of neurological causes is essential when symptoms are atypical, asymmetrical, or the illness is treatment-refractory. In the literature, only a few cases of HD describe RLS as the initial manifestation, for which awareness is critical. Timely identification can lead to genetic counseling and a collaborative approach to management. This abstract is funded by: None
Archila et al. (Fri,) studied this question.