Restless legs syndrome in DNAJC12 deficiency

Area of Science:

• Neuroscience
• Metabolic Disorders
• Genetics

Background:

• Restless Legs Syndrome (RLS) involves lower limb sensations relieved by movement, potentially linked to dopaminergic system dysfunction.
• DNAJC12 deficiency is an inherited metabolic disorder causing hyperphenylalaninemia and impaired neurotransmission.
• Previous reports detail a range of clinical symptoms in 43 identified DNAJC12 deficiency patients.

Purpose of the Study:

• To identify and report Restless Legs Syndrome (RLS) as a novel clinical manifestation of DNAJC12 deficiency.
• To evaluate the efficacy of dopaminergic medication in treating RLS in DNAJC12 deficiency patients.
• To assess the impact of treatment on dopaminergic homeostasis in these patients.

Main Methods:

• Longitudinal follow-up of two adult patients with DNAJC12 deficiency.
• Observation of RLS symptoms during L-dopa treatment.
• Introduction of low-dose pramipexole for RLS management.
• Monitoring of clinical improvement and peripheral short prolactin profiles to assess dopaminergic homeostasis.

Main Results:

• Restless Legs Syndrome (RLS) was identified as a new clinical manifestation in two adult patients with DNAJC12 deficiency.
• Adjunctive low-dose pramipexole treatment was effective in alleviating RLS symptoms.
• Treatment led to clinical improvement and stabilization of dopaminergic homeostasis, indicated by prolactin profiles.

Conclusions:

• Restless Legs Syndrome (RLS) should be considered a new, treatable clinical manifestation of DNAJC12 deficiency.
• These findings suggest that screening for DNAJC12 deficiency may be beneficial for patients with idiopathic RLS.