Schmid Type Metaphyseal Chondrodysplasia in a Large Single Genetic Lineage

Several subtypes of metaphyseal chondrodysplasia exist, of which the Schmid type is the most common. Characteristics include short limbed dwarfism, coxa vara, genu vara, and waddling gait. Skull, spine, and upper extremity involvement is minimal and often nonexistent. The primary defect involves a mutation affecting the metaphyseal portion of the growth plate, while the epiphysis is normal. A large single lineage family with metaphyseal chondrodysplasia, Schmid type (MCDS) was investigated. A genetic pedigree of 135 members of this family showed autosomal dominant inheritance between all 42 affected members. The large sample size allowed for the characterization of a broad range of features present in cases of MCDS. The majority of affected patients exhibited coxa vara with an average neck/shaft angle of 105 degrees. Despite coxa vara, premature osteoarthritis of the hip is not a feature of MCDS. Genu varum is the most prevalent knee disorder in this group, but greater than 30% of patients may exhibit genu valgum. This manuscript highlights MCDS background information, differential diagnoses, treatment options, and prognosis to aid in clinical decision-making.

A Brief Discussion on Chinese Medicine Behaviour and Prescription Compatibility

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.

PEX6: An Imaging Overlap Between Peroxisomal and Lysosomal Storage Diseases

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.