Why the study?
Only eight pediatric patients had been reported with biallelic ALPK3 pathogenic variants, leaving the broader clinical and molecular phenotypic spectrum poorly characterized.
This study expands the phenotypic spectrum of ALPK3-related cardiomyopathy, demonstrating that presentation can extend from infancy to the fourth decade with varying severity.
May warrant ALPK3 testing in pediatric cardiomyopathy; extends phenotypic spectrum but remains hypothesis-generating.
Cardiomyopathies are clinically heterogeneous disorders and are the leading cause of cardiovascular morbidity and mortality. Different etiologies have a significant impact on prognosis. Recently, novel biallelic loss-of-function pathogenic variants in alpha-kinase 3 (ALPK3) were implicated in causing early-onset pediatric cardiomyopathy (cardiomyopathy, familial hypertrophic 27; OMIM 618052). To date, eight patients, all presented during early childhood, were reported with biallelic ALPK3 pathogenic variants. We describe the molecular and clinical phenotype characterization of familial cardiomyopathy on one family with six affected individuals. We identified homozygosity for an ALPK3 deleterious sequence variant (NM_020778.4:c.639G>A:p.Trp213*) in all the affected individuals. They presented with either dilated cardiomyopathy that progressed to hypertrophic cardiomyopathy (HCM) or HCM with left ventricular noncompaction. The age of presentation in our cohort extends between infancy to the fourth decade. The phenotypic severity decreases with the progression of age.
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Senaidi et al. (2019) studied this question.
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