Emerging trends in management of propionic acidemia

Rafique, Muhammad

doi:10.1590/0004-2730000002821

Cited by 9 publications

(11 citation statements)

References 12 publications

(34 reference statements)

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“…Some patients are treated with cycles of enteral antibiotics (metronidazole) to reduce the burden of propiogenic gut flora [36, 161, 173, 183]. Some brittle patients with chronic hyperammonemia may be treated orally with sodium benzoate or sodium phenylbutyrate (Buphenyl) at 10 grams/m 2 /day, with careful monitoring of amino acid levels and electrolytes [12, 36].…”

Section: Medical Managementmentioning

confidence: 99%

Methylmalonic and propionic acidemias: clinical management update

Fraser

Venditti

2016

Current Opinion in Pediatrics

160

158

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Purpose of review Recent clinical studies and management guidelines for the treatment of the organic acidopathies methylmalonic acidemia (MMA) and propionic acidemia (PA) address the scope of interventions to maximize health and quality of life. Unfortunately, these disorders continue to cause significant morbidity and mortality due to acute and chronic systemic and end-organ injury. Recent findings Dietary management with medical foods has been a mainstay of therapy for decades, yet well controlled patients can manifest growth, development, cardiac, ophthalmological, renal and neurological complications. Patients with organic acidopathies suffer metabolic brain injury which targets specific regions of the basal ganglia in a distinctive pattern, and these injuries may occur even with optimal management during metabolic stress. Liver transplantation has improved quality of life and metabolic stability, yet transplantation in this population does not entirely prevent brain injury or the development of optic neuropathy and cardiac disease. Summary Management guidelines should identify necessary screening for patients with MMA and PA, and improve anticipatory management of progressive end-organ disease. Liver transplantation improves overall metabolic control, but injury to non-regenerative tissues may not be mitigated. Continued use of medical foods in these patients requires prospective studies to demonstrate evidence of benefit in a controlled manner.

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Section: Medical Managementmentioning

confidence: 99%

Methylmalonic and propionic acidemias: clinical management update

Fraser

Venditti

2016

Current Opinion in Pediatrics

160

158

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“…Although the overall clinical presentation of patients with this genotype is not too distinct from the reported classical clinical course of early onset PA [[33], [34], [35]], several observations are summarized below based on the longitudinal follow up of patients up to almost 20 years: a) all patients present in the neonatal period with symptoms of poor feeding, vomiting, lethargy, hypotonia, tachypnoea, variable metabolic acidosis compensated by respiratory alkalosis. The condition proceeds rapidly to acute encephalopathy characterized by variably depressed level of consciousness eventually leading to coma.…”

Section: Results and Discusionmentioning

confidence: 99%

Spectrum of mutations underlying Propionic acidemia and further insight into a genotype-phenotype correlation for the common mutation in Saudi Arabia

Al‐Hamed

Imtiaz

Al‐Hassnan

et al. 2019

Molecular Genetics and Metabolism Reports

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Propionic acidemia (PA) is an autosomal recessive metabolic disorder. PA is characterized by deficiency of the mitochondrial enzyme propionyl CoA carboxylase (PCC) that results in the accumulation of propionic acid. Alpha and beta subunits of the PCC enzyme are encoded by the PCCA and PCCB genes, respectively. Pathogenic variants in PCCA or PCCB disrupt the function of the PCC enzyme preventing the proper breakdown of certain amino acids and metabolites. To determine the frequency of pathogenic variants in PA in our population, 84 Saudi Arabian patients affected with PA were sequenced for both the PCCA and PCCB genes. We found that variants in PCCA accounted for 81% of our cohort (68 patients), while variants in PCCB only accounted for 19% (16 patients). In total, sixteen different sequence variants were detected in the study, where 7 were found in PCCA and 9 in PCCB . The pathogenic variant (c.425G > A; p.Gly142Asp) in PCCA is the most common cause of PA in our cohort and was found in 59 families (70.2%), followed by the frameshift variant (c.990dupT; p.E331Xfs*1) in PCCB that was found in 7 families (8.3%). The p.Gly142Asp missense variant is likely to be a founder pathogenic variant in patients of Saudi Arabian tribal origin and is associated with a severe phenotype. All variants were inherited in a homozygous state except for one family who was compound heterozygous. A total of 11 novel pathogenic variants were detected in this study thereby increasing the known spectrum of pathogenic variants in the PCCA and PCCB genes.

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“…3 En la actualidad, no existe tratamiento curativo para la AP, por lo que el manejo es sintomático, con dieta baja en proteínas de alta energía o el suplemento con mezclas específicas libres de sustratos propiogénicos o precursores del propionil CoA, como los aminoácidos de cadena ramificada (valina, isoleucina, metionina, treonina) y ácidos grasos de cadena impar, 6,8 con el objeto de minimizar la producción de metabolitos tóxicos. 5 Se debe aumentar la ingesta de carbohidratos, evitar largos períodos de ayuno, suplir con L-carnitina para eliminar el exceso de ácido propiónico, 4,5,7 emplear laxantes para tratar o prevenir la constipación y antibióticos (metronidazol) para prevenir el sobrecrecimiento bacteriano. 4 El trasplante de hígado se ha usado para mejorar los síntomas de la hiperamonemia, 7 la supervivencia, la calidad de vida, para prevenir el deterioro neurológico 12 y para la reversión de la cardiomiopatía.…”

Section: A a C U M U L A C I ó N D E á C I D O S O R G á N I C O S unclassified

“…5 Se debe aumentar la ingesta de carbohidratos, evitar largos períodos de ayuno, suplir con L-carnitina para eliminar el exceso de ácido propiónico, 4,5,7 emplear laxantes para tratar o prevenir la constipación y antibióticos (metronidazol) para prevenir el sobrecrecimiento bacteriano. 4 El trasplante de hígado se ha usado para mejorar los síntomas de la hiperamonemia, 7 la supervivencia, la calidad de vida, para prevenir el deterioro neurológico 12 y para la reversión de la cardiomiopatía. 13 Sin embargo, estos solo mejoran parcialmente los síntomas y el resultado general en la forma grave sigue siendo decepcionante.…”

Section: A a C U M U L A C I ó N D E á C I D O S O R G á N I C O S unclassified

“…La segunda forma de aparición es la tardía o progresiva crónica, la cual muestra retardo en el crecimiento y del desarrollo. 3,[6][7][8][9] Esta entidad se asocia, por lo general, con complicaciones neurológicas; 2,3,7,8 además, puede presentar miocardiopatía, 2,8 mayormente dilatada. Se ha asociado con el síndrome de QT largo, 2 alteraciones gastrointestinales, renales, hematológicas, inmunológicas, dermatológicas 3,10 y trastorno del espectro autista.…”

Section: Introductionunclassified

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Hallazgos clínicos, bioquímicos y moleculares de la acidemia propiónica. Reporte de un caso

et al. 2019

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Presentación de casos clínicos RESUMEN La acidemia propiónica es un trastorno infrecuente con patrón de herencia autosómico recesivo causado por la deficiencia de la enzima mitocondrial propionil-CoA carboxilasa, que convierte el propionil-CoA a D-metilmalonil-CoA. Se expone el caso de un recién nacido masculino con signos de dificultad respiratoria, vómitos y cansancio durante la alimentación. Presentó acidosis metabólica, cuerpos cetónicos en el suero y la orina positivos, hiperamonemia, anemia, trombocitopenia e hipoproteinemia. El estudio bioquímico por cromatografía de gases acoplada a espectrometría de masas en la muestra de orina fue sugestivo de acidemia propiónica. El estudio molecular en el gen PCCA encontró las mutaciones c.893A>G (p.K298R) en el padre y c.937C>T (p.R313X) en la madre. Existe la necesidad de establecer el diagnóstico de esta entidad infrecuente para implementar las medidas terapéuticas disponibles y aportar el oportuno asesoramiento genético.

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Emerging trends in management of propionic acidemia

Cited by 9 publications

References 12 publications

Methylmalonic and propionic acidemias: clinical management update

Methylmalonic and propionic acidemias: clinical management update

Spectrum of mutations underlying Propionic acidemia and further insight into a genotype-phenotype correlation for the common mutation in Saudi Arabia

Hallazgos clínicos, bioquímicos y moleculares de la acidemia propiónica. Reporte de un caso

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