Pyrophosphatase 2 Deficiency: Clinical Presentation, Diagnosis and Management.

PPA2

Biallelic PPA2 variants affecting a mitochondrial enzyme producing orthophosphate in the matrix; decompensation after viral illness or alcohol exposure

This retrospective cohort study compiles published and unpublished records of 93 individuals from 53 families with pyrophosphatase 2 deficiency, caused by biallelic PPA2 variants, including 14 families not previously reported. Presentation is invariably acute (fatigue, vomiting, seizures, collapse), with sudden cardiac death or acute heart failure after common viral illnesses in infants and toddlers, or after small amounts of alcohol in teenagers, and high mortality. Drawing on a worldwide survey of treating clinicians, the authors compile protocols for emergency and ongoing management. They also note a pronounced inheritance rate of pathogenic alleles from carrier parents, which remains to be confirmed.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A reference article for a rare emergency: in sudden death or acute heart failure following a viral illness in a young child, or a severe collapse after a small amount of alcohol in a teenager, PPA2 should be queried in the exome or genome, including post mortem. The proposed protocols rest on a survey of clinicians, not on comparative efficacy data. In practice, the key issue is identifying still-asymptomatic biallelic relatives, for whom viral illness and alcohol are the described triggers.

Analysis by Dr Thibaut Benquey