Parkinson’s disease (PD) is recognized as a neurodegenerative condition. Parkin mutations cause approximately 50% of familial young-onset PD and 15-20% of sporadic young-onset PD. 

Etiologies to consider for early-onset parkinsonism include Huntington disease, neuroacanthocytosis, Wilson’s disease, dopa-responsive dystonia, drug-induced parkinsonism, infectious/postinfectious and structural causes. Rarely, certain mutations can be associated to parkinsonian syndromes.  

A 44-year-old female developed progressive motor, speech and cognitive impairment with associated recurrent falls with onset at around age 20. Family history is remarkable for parental consanguinity (first cousins). Examination demonstrates supranuclear gaze palsy, bradykinesia, intermittent rest tremor, spasticity, facial-faucial-finger mini-myoclonus, hyperreflexia, scissoring of gait and axial instability. After extensive work-up with laboratories that included but was not limited to serum ceruloplasmin, urine copper and CPK; unremarkable electrodiagnostic testing and brain MRI showing diffuse volume loss, genetic testing was requested. Whole-genome sequencing showed a homozygous likely pathogenic variant in the ATP13A2 gene. Defects in ATP13A2 gene and the clinical phenotype of our patient are consistent with Kufor-Rakeb Syndrome(KRS). Carbidopa-Levodopa 25 mg TID was started and re-evaluation done at 1 month. A remarkable improvement of dysphagia, cessation of rest tremor and facial movements, and a mild improvement in axial instability was reported. As a result she had increased capability to help with transfers and became more independent in the activities of daily living.  

Kufor-Rakeb Syndrome is a rare autosomal recessive form of early-onset  parkinsonian syndrome (PARK9). A mutation in ATP13A2, causing impairment mitochondrial homeostasis, and lysosomal type 5 ATPase function leads to this syndrome. Clinical presentation includes behavioral problems, facial tremor, parkinsonian features, pyramidal tract dysfunction, supranuclear gaze palsy, and cognitive decline. Treatment with carbidopa-levodopa can result in improvement of symptoms and better quality of life. Therefore, it is important to recognize this syndrome and consider genetic testing in the evaluation of patients with early onset parkinsonism.