RESUMO
Biallelic variants in PPA2 gene cause a rare but lethal mitochondrial disorder. We describe the first four cases reported in Spain of PPA2 disease in two unrelated families. We have conducted a revision of the clinical history, necropsies, and postmortem genetic testing from probands, and clinical evaluation, genetic testing and blood transcript analysis in family members. All the cases harbored biallelic PPA2 variants in compound heterozygous status. Two brothers from family 1 suffered sudden death after a small first intake of alcohol in 2013 and 2022. The sister remains alive but affected with cardiomyopathy, extensive scar on cardiac imaging, and high sensitivity to alcohol intake. The three siblings carried PPA2 c.290A > G (p.Glu97Gly) novel missense variant and PPA2 c.513C > T (p.Cys171 = ) altering splicing site variant, both probably leading to mRNA degradation based on in-silico and transcript analyses. A teenager from family 2 suffered sudden death after a small intake of alcohol in 2018 and carried PPA2 c.683C > T (p.Pro228Leu) missense and PPA2 c.980_983del (p.Gln327fs) novel frameshift variant, both probably leading to abnormal protein structure. All cases were asymptomatic until adolescence. Furthermore, the sister in family 1 has survived as an asymptomatic adult. PPA2 disease can manifest as cardiac arrest in the young, especially after alcohol exposure. Our results show that PPA2 deficiency can be related to different pathogenicity mechanisms such as abnormal protein structure but also mRNA decay caused by synonymous or missense variants. Strict avoidance of alcohol consumption and early defibrillator implantation might prevent lethal arrhythmias in patients at risk.
Assuntos
Consumo de Bebidas Alcoólicas , Morte Súbita Cardíaca , Pirofosfatase Inorgânica , Proteínas Mitocondriais , Adolescente , Adulto , Feminino , Humanos , Masculino , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/efeitos adversos , Morte Súbita Cardíaca/etiologia , Mutação de Sentido Incorreto , Linhagem , Espanha , Proteínas Mitocondriais/genética , Pirofosfatase Inorgânica/genéticaRESUMO
No disponible
Assuntos
Humanos , Feminino , Lactente , Miocardite , Bloqueio Atrioventricular , Bronquiolite , Unidades de Terapia Intensiva , Respiração ArtificialRESUMO
La ventana aortopulmonar es una causa poco frecuente de insuficiencia cardiaca en el neonato. Debe ser descartada en caso de existir edema pulmonar sin los shunts izquierda-derecha más frecuentes. Presentamos las imágenes ecocardiográficas de un recién nacido que ingresó con clínica de insuficiencia cardiaca en nuestra institución.
The aortopulmonary window is a rare cause of heart failure in the neonate. It must be ruled out if there are signs of pulmonary edema without the most frequents left-right shunts. We report the echocardiographic images of a newborn who was admitted with symptoms of heart failure at our institution.
Assuntos
Humanos , Feminino , Recém-Nascido , Defeito do Septo Aortopulmonar/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico por imagem , Defeito do Septo Aortopulmonar/complicações , Ultrassonografia , Insuficiência Cardíaca/etiologiaRESUMO
The aortopulmonary window is a rare cause of heart failure in the neonate. It must be ruled out if there are signs of pulmonary edema without the most frequent left-right shunts. We report the echocardiographic images of a newborn who was admitted with symptoms of heart failure at our institution.
Assuntos
Defeito do Septo Aortopulmonar/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico por imagem , Defeito do Septo Aortopulmonar/complicações , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Recém-Nascido , UltrassonografiaRESUMO
Describimos un caso de síndrome SAPHO (sinovitis, acné, pustulosis, hiperostosis y osteítis) con una forma de presentación poco habitual, en una niña de 14 años de edad con febrícula de 8 meses de duración, dolor lumbar izquierdo y reactantes de fase aguda elevados con anemia normocítica y normocrómica. En una radiografía de miembros inferiores se evidenció una imagen lítica con osteítis e hiperostosis en peroné derecho, como hallazgo casual tras una caída accidental. Estos datos, además del acné, la pustulosis, la artritis esternoclavicular y los estudios obtenidos por resonancia magnética (RM) de columna y gammagrafía ósea, orientaron el diagnóstico de SAPHO (AU)
We describe a case of SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) with an unusual presentation in a 14 year-old girl with low grade fever which lasts 8 months, left low back pain and elevated erythrocyte sedimentation rates and protein C-reactive with chronic anaemia. A radiograhy of the lower limbs showed a lytic image with osteitis and hyperostose in the right fibula, as a casual finding. This information, in addition to the acne, pustulosis, sternoclavicular arthritis and the studies got from the magnetic resonance image (MR) of spine, pointed out the diagnosis of SAPHO (AU)
Assuntos
Humanos , Feminino , Adolescente , Síndrome de Hiperostose Adquirida/diagnóstico , Doenças Reumáticas/complicações , Acne Vulgar/etiologia , Proteínas de Fase Aguda , Febre/etiologiaRESUMO
We describe a case of SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) with an unusual presentation in a 14 year-old girl with low grade fever which lasts 8 months, left low back pain and elevated erythrocyte sedimentation rates and protein C-reactive with chronic anaemia. A radiograhy of the lower limbs showed a lytic image with osteitis and hyperostose in the right fibula, as a casual finding. This information, in addition to the acne, pustulosis, sternoclavicular arthritis and the studies got from the magnetic resonance image (MR) of spine, pointed out the diagnosis of SAPHO.
