2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-PPA2 Deficiency Phenotype

Pdf Summary

This abstract discusses a case report on PPA2 deficiency, a genetic condition caused by mutations in the PPA2 gene. The PPA2 gene is responsible for converting pyrophosphate into inorganic phosphate in mitochondria. Pathologic variants in PPA2 have been linked to sudden cardiac arrhythmia death and cardiomyopathy.<br /><br />The case presented in this report is about a 16-year-old male who experienced sudden cardiac arrest while playing basketball. He had a history of digital ulcers, muscle contracture and atrophy, and atypical Raynaud's phenomenon. Cardiac testing revealed abnormalities such as apical hypokinesis and global hypokinesis. Genetic testing identified a variant in the PPA2 gene, which is suspected to be the cause of the patient's cardiac arrhythmia.<br /><br />Histology and electron microscopy showed evidence of capillaritis, a condition characterized by inflammation and narrowing of capillaries, in both skeletal and cardiac muscle. This finding suggests that capillaritis may be an important feature of PPA2 deficiency, contributing to the broader phenotype of the condition.<br /><br />Further testing on the patient's fibroblasts confirmed a functional deficiency of PPA2, with low protein amount and enzyme activity. The patient's findings primarily matched endothelial cell metabolic dysfunction, and myopathy appeared to be secondary.<br /><br />The abstract also mentions previous studies that have described families with PPA2 variants and associated cardiac and neurological symptoms. All identified cases so far have been homozygous or biallelic compound heterozygous.<br /><br />In summary, this case report highlights the importance of PPA2 deficiency in sudden cardiac events and cardiomyopathy. It also suggests that capillaritis may be an unrecognized feature of the condition. Further research is needed to understand the mechanism of injury in PPA2 deficiency.

Asset Subtitle

Presenting Author - donna novacic, MD; Co-Author - William A. Gahl, MD, Ph.D; Co-Author - Johan LK. Van Hove, MD PhD, MBA; Co-Author - Marisa W. Friederich W. Friederich, PhD; Co-Author - Dana K. Strode, BS; Co-Author - Roxanne A. Van Hove, BS;

Meta Tag

Sequencing

Polymorphism

Phenotypic delineation of disorders

Phenotype

Pathology

Pathogenesis

Musculoskeletal system

Mitochondria

Metabolic Disorder

Genome sequencing

Genetic Testing

Clinical History

Cardiovascular System

Cardiac/circulatory disorders

Bioinformatics

Co-Author Roxanne A. Van Hove, BS

Co-Author Dana K. Strode, BS

Co-Author Marisa W. Friederich W. Friederich, PhD

Co-Author Johan LK. Van Hove, MD PhD, MBA

Co-Author William A. Gahl, MD, Ph.D

Presenting Author donna novacic, MD

Keywords

PPA2 deficiency

genetic condition

mutations

PPA2 gene

sudden cardiac arrhythmia death

cardiomyopathy

capillaritis

fibroblasts

endothelial cell metabolic dysfunction

myopathy