Chediak-Higashi syndrome presenting as pure juvenile Parkinsonism

Case presentation: Here we present a Brazilian patient with juvenile parkinsonism as the sole manifestation of a new LYST mutation. His parents were consanguineous and he had a sister with clinical diagnosis of Chediak-Higashi syndrome based on bleeding diathesis, immunodeficiency and inclusion bodies in peripheral blood leukocytes. He began with asymmetrical parkinsonism when he was 15 years old characterized by bradykinesia, rigidity and resting tremor. By that time, he began treatment with levodopa with a good clinical response. During follow-up the patient developed motor fluctuations, an important impulse control disorder and cognitive decline. His current clinical evaluation had an UPDRS-III score of 64 and a 11/30 on the MoCA test. He was submitted to whole-exome sequencing, with the finding of a homozygous missense mutation p.R3107H in the LYST gene. Discussion: Chédiak-Higashi syndrome is a lysosomal storage disorder caused by mutations in the LYST gene with an autosomal recessive inheritance. It is characterized by the disruption of transport and fusion of lysosomes, leading to a myriad of clinical signs and symptoms. Clinically patients manifest variable degrees of partial oculocutaneous albinism, bleeding diathesis and immunodeficiency. Depending on the age of symptoms onset, cases manifesting during childhood have mainly hematological symptoms, while the ones who present in adolescence/early-adulthood usually display neurological symptoms. The latter may include parkinsonism, cerebellar ataxia, dystonia, dementia, neuropathy and epilepsy, with a prolonged clinical course and slow deterioration. Final comments: As far as we know, this is the first reported case of homozygous missense mutation p.R3107H in the LYST gene, with an atypical presentation characterized by early-onset parkinsonism without associated hematological disease.