Patient Affected by Beta-Propeller Protein-Associated Neurodegeneration: A Therapeutic Attempt with Iron Chelation Therapy

Abstract

Here, we report the case of a 36-year-old patient with a diagnosis of de novo mutation of the WDR45 gene, responsible for beta-propeller protein-associated neurodegeneration, a phenotypically distinct, X-linked dominant form of Neurodegeneration with Brain Iron Accumulation. The clinical history is characterized by a relatively stable intellectual disability and a hypo-bradykinetic and hypertonic syndrome with juvenile onset. Genetic investigations and T1 and T2-weighted MR images align with what is described in literature. The patient was also subjected to PET with 18-FDG investigation and DaT-Scan study. In reporting relevant clinical data, we want to emphasize the fact that the patient received a chelation therapy with deferiprone (treatment already used in other forms of NBIA with encouraging results), which, however, had to be interrupted because the parkinsonian symptoms worsened. Conversely, the patient has benefited from non-drug therapies and, in particular, from an adapted motor activity with assisted pedaling (method in the process of validation in treatments of parkinsonian syndromes), which started before the treatment with deferiprone and still continues.

New Perspectives in Iron Chelation Therapy for the Treatment of Neurodegenerative Diseases

“…Indeed, excessive iron depletion could result in cognitive decline, by decreasing the activity of enzymes and iron-containing complexes [122,123] and the synthesis of neurotransmitters, such as dopamine, norepinephrine and serotonin [37,124,125,126]. Fortunately, cognitive decline has not been reported in clinical chelation trials for neurodegenerative diseases using therapeutic concentrations of deferasirox, deferiprone, PBT1 or PBT2 [115,116,117,118,119,121,127,128].…”

Parkinson’s Disease and Metal Storage Disorders: A Systematic Review

“… Fonderico, M. et al, 2017. [ 56 ] Case report BPAN 1F 26 NA NA ✓ Mild typical parkinsonism. Gasca-Salas, C. et al, 2017.…”

Childhood Dystonia-Parkinsonism Following Infantile Spasms—Clinical Clue to Diagnosis in Early Beta-Propeller Protein-Associated Neurodegeneration

“…Iron chelation therapy with deferiprone, being introduced in pantothenate kinase-associated neurodegeneration (PKAN)- NBIA treatment, worsened parkinsonism in one Italian case of adulthood BPAN. 26 An early diagnosis can be attained by genetic testing of NBIA diseases in cases of early-onset encephalopathy syndrome, infantile spasms, or Rett-like characteristics. Additional diagnostic tools, for example, T2w or sensitive SWI-MRI of GP and SN, could help complete the clinical picture of the disease, while symptoms such as hypertonic muscles and parkinsonism may emerge only later, when medical intervention for parkinsonian symptoms is already necessary.…”