Biochemical and genetic analysis of Restless Legs syndrome (RLS): A pilot study

Objectives Restless Leg Syndrome (RLS) is a neurological disorder characterized by an uncontrollable urge to move the legs, often worsening at night, leading to insomnia and discomfort. RLS is linked to genetic factors, defects in iron metabolism, dopaminergic dysfunction, and disturbances in the central opiate system. Specific genetic variants, including MEIS1, BTBD9, PTPRD, and MAP2K5/SCOR1, affect dopamine synthesis, iron transport, and neuroprotection. Research on RLS prevalence and its underlying causes in India is limited, highlighting the need for more in-depth genetic and biochemical studies to improve diagnosis and treatment. Material and Methods A hundred suspected RLS patients were screened at AIIMS Bhopal’s Pulmonary Medicine department. After obtaining consent, 36 confirmed RLS cases and age-matched healthy controls were enrolled. Blood samples were collected for fasting blood sugar (FBS), liver function tests (LFT), renal function tests (RFT), serum ferritin, and iron analysis using an auto-analyzer. Genotyping for single nucleotide polymorphisms (SNPs) was performed using ARMS-PCR. Results RLS significantly impacts daily life, contributing to insomnia, irritability, and other comorbidities. The study revealed lower iron levels in RLS patients, suggesting a potential secondary form of the condition linked to iron deficiency. Variations in serum iron, total iron-binding capacity, iron saturation, and ferritin further underscore the relationship between iron metabolism and RLS. Genetic analysis identified SNPs in genes such as MEIS1, TOX3, and PTPRD, potentially contributing to RLS. Although no specific at-risk alleles were prevalent, heterozygous mutations, particularly at the T allele, suggested a possible genetic predisposition that may exacerbate RLS. Conclusion This study supports the iron-dopamine hypothesis, linking RLS to brain iron deficiency that disrupts dopamine signaling. Genetic factors may further aggravate this disruption. Understanding the interplay between iron levels and dopaminergic function is crucial for effectively managing both primary and secondary RLS, aiding the development of better long-term treatment strategies.