Vol 2-2 Case Report

PEX6: An Imaging Overlap Between Peroxisomal and Lysosomal Storage Diseases

César Augusto Pinheiro Ferreira Alves1,3*, Luisa Norbert Simonsen2, Jonathan Rodrigues1, Isabella Peixoto de Barcelos2, Clarissa Bueno2, Ramon Moura Dos Santos1, Fernando Kok2,4, Leandro Tavares Lucato1

1Neuroradiology Section, Hospital das Clínicas da Universidade de São Paulo, Brazil

2Neurogenetics Unit Neurology Department, Hospital das Clínicas da Universidade de São Paulo, Brazil

3Division of Neuroradiology, Department of Radiology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

4Mendelics Genomic Analysis, São Paulo, SP, Brazil

Peroxisomal disorders are a group of expanding genetic diseases divided into two major categories: peroxisome biogenesis defects (Zellweger spectrum disorder), and single enzymatic defects. Disorders of Peroxisome Biogenesis occur when there are biallelic pathogenic variants in any of the 13 PEX genes, which code for the peroxins, proteins required for peroxisome biogenesis. This group of disorders includes two distinct phenotypes: Rhizomelic Chondrodysplasia Punctata Type-1 and Zellweger Spectrum Disorders (ZSD), of which Zellweger syndrome is the most severe, neonatal adrenoleukodystrophy is intermediate, and infantile Refsum is the mildest. The spectrum’s most frequent defects are observed in the proteins PEX1 and PEX6, and the most common clinical presentation is Zellweger spectrum, which is often associated with craniofacial dysmorphism with neurologic abnormalities. Typically, the neuroimaging pattern shows several malformative features, including a range of cortical gyral abnormalities such as microgyria and pachygyria, and impairment of the myelination. Nevertheless, we report two siblings with peroxisomal disorder, with unexpected leukodystrophy pattern of the brain mimicking lysosomal storage disease, with classical imaging features of Krabbe disease on brain magnetic resonance image.

By whole exome sequencing, we identified two pathogenic variants in compound heterozygosity in PEX6: Chr6:42.933.455 C>T (c.2435G>A), and Chr6:42.935.188 C>T (c.1802G>A). Thus, a final diagnosis of peroxisome disorder was confirmed. The index cases highlight the importance of considering peroxisome disorders as a differential diagnosis for patients with imaging features that resemble Krabbe disease.

DOI: 10.29245/2690-0009/2020/2.1117 View / Download Pdf
Vol 2-2 Review Article

A Brief Discussion on Chinese Medicine Behaviour and Prescription Compatibility

Loh Cheng Toa Steven1, Goh Xin Yi1*

1NTU Chinese Medicine Clinic, Nanyang Technological University, Singapore, Singapore

Chinese medicine (CM) is gaining popularity in recent years, prompting researchers’ and clinicians’ interest and effort into the makings and effects of it, especially after the announcement of World Health Organisation’s incorporation of CM into the mainstream medical compendium, followed by the promising outcome brought about by the implementation of CM in the recent pandemic. Individual herb has complex properties, coming from its pharmacological properties and the Chinese medical principles of organ-directed, taste and dynamic orientational behaviours. The use of individual herb in CM prescription is rare. Formula prescriptions predominantly consist of two ingredients or more. To fully reveal the effects of CM is a great challenge. The compound reaction of various herbs, the absorption and utility rate by the body, uniqueness of individual physique, sub-types of pathological behaviours and time-line progression at the healing process add on to the complexity of understanding the full effect of CM. Various theories such as pathophysiology guidance, pharmacokinetic-pharmacodynamic compatibility method, and Global Systems Biology for Integrative Genomics, Proteomics and Metabolomics, which interactively provide a more comprehensive and greater in-depth understanding, together with the consideration of development timeline, may shed more light to revealing the full picture of the effects of compatibility prescription.

DOI: 10.29245/2690-0009/2020/2.1116 View / Download Pdf
Vol 2-2 Review Article

Yeast contributions to Alzheimer’s Disease

Jamieson B Mcdonald, Sudip Dhakal, Ian G Macreadie*

School of Science, RMIT University, Bundoora, Victoria, Australia

Alzheimer’s Disease is a highly prevalent, age-related, neurodegenerative disease associated with the accumulation of toxic proteins, including amyloid beta and tau, that affect important cellular functions. Through the study of these proteins in yeast over the past 2 decades, the effects of amyloid beta oligomerization and aggregation, and tau hyperphosphorylation on basic cellular functions, such as ageing, oxidative stress, cell cycling and proteostasis have been observed. Strategies for the prevention of damage by these proteins can be explored, thanks to the exquisite array of technologies available for yeast studies. This review summarises existing knowledge of Alzheimer’s Disease, the work over the past two decades on yeast models for Alzheimer’s Disease and how these models contribute to the development of treatments and preventative strategies for Alzheimer’s Disease.

DOI: 10.29245/2690-0009/2020/2.1114 View / Download Pdf