TY - JOUR
T1 - PLA2G6-associated neurodegeneration in four different populations-case series and literature review
AU - Hanna Al-Shaikh, Rana
AU - Milanowski, Lukasz M.
AU - Holla, Vikram V.
AU - Kurihara, Kanako
AU - Yadav, Ravi
AU - Kamble, Nitish
AU - Muthusamy, Babylakshmi
AU - Bellad, Anikha
AU - Koziorowski, Dariusz
AU - Szlufik, Stanislaw
AU - Hoffman-Zacharska, Dorota
AU - Fujioka, Shinsuke
AU - Tsuboi, Yoshio
AU - Ross, Owen A.
AU - Wierenga, Klaas
AU - Uitti, Ryan J.
AU - Wszolek, Zbigniew
AU - Pal, Pramod Kumar
N1 - Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/8
Y1 - 2022/8
N2 - Background: PLA2G6-Associated Neurodegeneration, PLAN, is subdivided into: Infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, and adult-onset dystonia parkinsonism [1]. It is elicited by a biallelic pathogenic variant in phospholipase A2 group VI (PLA2G6) gene. In this study we describe new cases and provide a comprehensive review of previously published cases. Methods: Eleven patients, from four different institutions and four different countries. All underwent a comprehensive chart review. Results: Ages at onset ranged from 1 to 36 years, with a median of 16 and a mean of 16.18 ± 11.91 years. Phenotypic characteristics were heterogenous and resembled that of patients with infantile neuroaxonal dystrophy (n = 2), atypical neuroaxonal dystrophy (n = 1), adult-onset dystonia parkinsonism (n = 1), complex hereditary spastic paraparesis (n = 3), and early onset Parkinson's disease (n = 2). Parental genetic studies were performed for all patients and confirmed with sanger sequencing in five. Visual evoked potential illustrated optic atrophy in P4. Mineralization was evident in brain magnetic resonance imaging of P1, P2, P4, P5, P7, and P11. Single photon emission computed tomography was conducted for three patients, revealed decreased perfusion in the occipital lobes for P10. DaTscan was performed for P11 and showed decreased uptake in the deep gray matter, bilateral caudate nuclei, and bilateral putamen. Positive response to Apomorphine was noted for P10 and to Baclofen in P2, and P3. Conclusions: PLAN encompasses a wide clinical spectrum. Age and symptom at onset are crucial when classifying patients. Reporting new variants is critical to draw more attention to this condition and identify biomarkers to arrive at potential therapeutics.
AB - Background: PLA2G6-Associated Neurodegeneration, PLAN, is subdivided into: Infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, and adult-onset dystonia parkinsonism [1]. It is elicited by a biallelic pathogenic variant in phospholipase A2 group VI (PLA2G6) gene. In this study we describe new cases and provide a comprehensive review of previously published cases. Methods: Eleven patients, from four different institutions and four different countries. All underwent a comprehensive chart review. Results: Ages at onset ranged from 1 to 36 years, with a median of 16 and a mean of 16.18 ± 11.91 years. Phenotypic characteristics were heterogenous and resembled that of patients with infantile neuroaxonal dystrophy (n = 2), atypical neuroaxonal dystrophy (n = 1), adult-onset dystonia parkinsonism (n = 1), complex hereditary spastic paraparesis (n = 3), and early onset Parkinson's disease (n = 2). Parental genetic studies were performed for all patients and confirmed with sanger sequencing in five. Visual evoked potential illustrated optic atrophy in P4. Mineralization was evident in brain magnetic resonance imaging of P1, P2, P4, P5, P7, and P11. Single photon emission computed tomography was conducted for three patients, revealed decreased perfusion in the occipital lobes for P10. DaTscan was performed for P11 and showed decreased uptake in the deep gray matter, bilateral caudate nuclei, and bilateral putamen. Positive response to Apomorphine was noted for P10 and to Baclofen in P2, and P3. Conclusions: PLAN encompasses a wide clinical spectrum. Age and symptom at onset are crucial when classifying patients. Reporting new variants is critical to draw more attention to this condition and identify biomarkers to arrive at potential therapeutics.
KW - Adult-onset dystonia parkinsonism
KW - Atypical neuroaxonal dystrophy
KW - Infantile neuroaxonal dystrophy
KW - Neurodegeneration with brain iron accumulation
KW - Phospholipase A2 group VI
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U2 - 10.1016/j.parkreldis.2022.06.016
DO - 10.1016/j.parkreldis.2022.06.016
M3 - Article
C2 - 35803092
AN - SCOPUS:85134425616
SN - 1353-8020
VL - 101
SP - 66
EP - 74
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -