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Abstract: Fucosidosis is a rare lysosomal storage disease. A 14-year-old girl is presented, with recurrent infections, progressive dystonic movement disorder and mental retardation with onset in early childhood. The clinical picture was also marked by mild morphologic features, but absent dysostosis multiplex and organomegaly. MRI images at 6.5 years of age were reminiscent of pallidal iron deposition (“eye-of-the-tiger” sign) seen in neurodegeneration with brain iron accumulation (NBIA) disorders. Progressively spreading angiokeratoma corporis diffusum led to the correct diagnosis. This case extends the scope of clinical and neuroradiological manifestations of fucosidosis. [Copyright &y& Elsevier]

Abstract: Background and aims: Infantile neuroaxonal dystrophy is a rare neurodegenerative disorder, with onset in the first 2 years of life. Mutations in the PLA2G6 gene were identified in patients with infantile neuroaxonal dystrophy. Our purpose was to review clinical, neurophysiologic, neuroradiologic and neuropathological features of our patients in order to identify the earliest signs of disease. We also correlate these data with the genotype in the mutation positive patients. Methods: We reviewed the clinical reports, neurophysiologic and neuropathological studies and brain imaging of our patients. In five patients molecular analysis of the PLA2G6 gene was performed. Results: We report 10 patients with infantile neuroaxonal dystrophy. Earliest symptoms presented between 6 and 18 months of age. The first manifestations were arrest in the acquisition of milestones or regression. The first neurological signs were generalized hypotonia and pyramidal signs. Fast rhythms on EEG were observed in all patients. Brain imaging studies showed cerebellar atrophy in all patients, with signal hyperintensity in the cerebellar cortex on T2-weighted images in five. All cases had characteristic axonal spheroids on skin biopsy. Mutations in the PLA2G6 gene were identified in the five patients studied. Three of them had the same homozygous mutations 2370T> G, Y790X. Conclusions: Though mutations were detected in the patients studied, a clear genotype–phenotype correlation could not be ascertained. In the appropriate clinical context, characteristic brain imaging and fast rhythms on EEG can support the decision to perform molecular analysis and avoid skin biopsy to confirm diagnosis. [Copyright &y& Elsevier]

Neurodegeneration with brain iron accumulation comprises a clinically and genetically heterogeneous collection of disorders that share key features. These include progressive neurological disease accompanied by high basal ganglia iron and axonal dystrophy. To date, 2 genetic forms have been associated with mutations in PANK2 and PLA2G6, both of which encode proteins that are critical to membrane integrity. The intersection of pathways perturbed by defects in these 2 genes now enables us to test hypotheses of a common pathogenesis and ask why iron accumulates. The mechanisms implicated may contribute to our understanding of more common neurodegenerative disorders with iron dyshomeostasis, including Parkinson and Alzheimer disease. [Copyright &y& Elsevier]

Background: Tauopathy and α‐synucleinopathy often occur together in human brain diseases but most commonly in the context of β‐amyloidosis. Tauopathy induced by α‐synucleinopathy in the absence of β‐amyloid has been demonstrated in vitro and in cultured cells but compelling examples of this in human disease rarely occur, most commonly in familial Parkinson's disease due to mutations in the α‐synuclein gene. Mitochondrial protein‐associated neurodegeneration (MPAN) due to mutations in C19orf12 produces neurodegeneration with brain iron accumulation as well as widespread α‐synucleinopathy. We report here on the findings and significance of associated tauopathy in MPAN. Method: Four patients with genetically confirmed MPAN were referred for brain autopsy and a complete histologic and immunohistochemical evaluation was undertaken for lesions and proteinopathies of common neurodegenerative diseases as well as the specific reported lesions of MPAN. Result: All patients had hallmark pathologic features of MPAN including atrophy, gliosis, and iron accumulation involving the globus pallidus as well as abundant α‐synucleinopathy manifest as Lewy bodies and neurites thoughout the brain. Tauopathy was present in each case with neurofibrillary tangles distributed in Braak stages I to V with pretangles and more widely distributed tau‐positive dystrophic neurites. The distribution and regional burden of tauopathy was less than that of α‐synucleinopathy in each case. β‐amyloid or TDP‐43 abnormalities were not identified in any case. Conclusion: The lesional burden and distribution in MPAN are consistent with a pathogenetic model in which dysmetabolism of α‐synuclein is sufficient, in the absence of other common neurodegenerative pathologies, to induce tauopathy. Study of rare familial diseases such as MPAN may enhance our understanding of the pathogenesis of more common idiopathic neurodegenerative diseases. [ABSTRACT FROM AUTHOR]