To register click here: https://attendee.gotowebinar.com/register/1345569576668745822

There are two presentations prepared:

1. Katelyn Brook - An atypical case of thalassaemia

Abstract: Epsilon gamma delta beta (εγδβ)⁰-thalassaemia, is a rare disorder caused by large deletions of the β-globin gene cluster. The disease usually presents as severe neonatal microcytic anaemia and, in adulthood, as β-thalassemia trait without increased levels of haemoglobin A2 (HbA2). Our patient presented with microcytic anaemia, polydactyly of the fifth finger, apnoeic episodes, tonic clonic seizures, and Kawasaki disease in the neonatal period. Molecular and cytogenetic studies identified a large 2.25Mb deletion, which included the entire β-globin gene cluster and the β-globin locus control region (LCR). To our knowledge, this patient’s deletion is larger than any other εγδβ⁰-thalassaemia variant currently described in the literature.

2. Isaac Bernhardt - Short-chain enoyl-CoA hydratase deficiency in Aotearoa

Short-chain enoyl-coA hydratase (SCEH) due to biallelic ECHS1 variants was first reported in 2014 in association with Leigh syndrome (LS) and increased S-(2-carboxypropyl)cysteine excretion. It is potentially treatable with a valine-restricted, high-energy diet and emergency regimen. In 2020, Simon et al. described four Samoan children harbouring a hypomorphic allele (c.489G>A, p.Pro163=) associated with reduced levels of normally-spliced mRNA. This synonymous variant, missed on standard genomic testing, is prevalent in the Samoan population (allele frequency 0.17), thus prompting a search for undiagnosed patients in Aotearoa and Australia with LS and one ECHS1 variant, with interrogation for the c.489G>A variant. Thirteen patients from 10 families were identified; all had Maori or Pacific ancestry. Excluding one pre-symptomatic infant, they had a recognisable phenotype with bilateral globus pallidi lesions and symptom-onset in early childhood. SCEH-related metabolites were non-diagnostic. Functional studies demonstrated skipping of exon four and markedly reduced ECHS1 protein. These data provide further support for the pathogenicity of this ECHS1 variant which is also prevalent in Maori, Cook Island Maori, and Tongan populations (allele frequency 0.14–0.24). It highlights the need to search for a second variant in apparent heterozygotes with an appropriate phenotype, and has implications for genetic counselling in family members who are heterozygous for the more severe ECHS1 alleles.