Mepolizumab -- therapeutic strategy for a paediatric patient with eosinophilic granulomatosis with polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) is classified as an anti-neutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis. It is a multisystem disorder and can affect every organ system. EGPA is a rare disease, with an estimated prevalence of 1/70,000–100,000 in Europe. As its onset usually occurs in adulthood, data from paediatric patients are limited. We present here a very rare practical EGPA clinical case involving a paediatric patient. Presently, data on mepolizumab usage in paediatric patients are limited, with only a few case reports published.

Study of an FBXO7 patient mutation reveals Fbxo7 and PI31 co-regulate proteasomes and mitochondria

Mutations in FBXO7 have been discovered associated with an atypical parkinsonism. We report here a new homozygous missense mutation in a paediatric patient that causes an L250P substitution in the dimerization domain of Fbxo7. This alteration selectively ablates the Fbxo7-PI31 interaction and causes a significant reduction in Fbxo7 and PI31 levels in patient cells. Consistent with their association with proteasomes, L250P patient fibroblasts have reduced proteasome activity and proteasome subunits. We also show PI31 interacts directly with the MiD49/51 fission adaptor proteins, and unexpectedly, PI31 acts as an adaptor enabling SCFFbxo7 ligase to ubiquitinate MiD49. Thus, the L250P mutation changes the function of Fbxo7 by altering its substrate repertoire. Although MiD49/51 expression was reduced in L250P patient cells, there was no effect on the mitochondrial network. However, patient cells had higher levels of ROS and reduced viability under stress. Our study shows that Fbxo7 and PI31 affect each other's functions in regulating both proteasomal and mitochondrial function and demonstrate a new function for PI31, as an adaptor for the SCFFbxo7 E3 ubiquitin ligase.

Dental manifestations of pseudo-vitamin-D deficiency rickets in a paediatric patient

Vitamin D–resistant rickets shows the resistance to vitamin D (Vit-D) therapy, which traditionally works well in cases with deficiency rickets. The signs start appearing as early as in the first month of life and are characterised by the defective mineralisation at the ends of cartilage and bones despite having normal Vit-D levels in the serum. This case report highlights the dental and maxillofacial manifestations in a 3-year-old girl diagnosed with pseudo-Vit-D deficiency rickets. The report also highlights the variations in the dental manifestations of the condition reported in the literature.