Determination of methylmalonyl coenzyme A by ultra high-performance liquid chromatography tandem mass spectrometry for measuring propionyl coenzyme A carboxylase activity in patients with propionic acidemia

Gotoh, Kana; Nakajima, Yoko; Tanaka, Go; Watanabe, Yoriko; Hotta, Yuji; Kataoka, Tomoya; Kawade, Yoshihiro; Sugiyama, Naruji; Ito, Tetsuya; Kimura, Kazunori; Maeda, Yasuhiro

doi:10.1016/j.jchromb.2017.02.003

Cited by 3 publications

(5 citation statements)

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“…La AP es causada por la baja actividad de la PCC, que produce la generación tóxica del ácido propiónico a partir de la propionil-CoA acumulado en la matriz de las mitocondrias. 8,9 Este defecto genera la acumulación de intermediarios metabólicos, como el ácido 3-hidroxipropiónico y metilcitrato en la orina y la propionilcarnitina en la sangre. La hiperamonemia descrita puede ser debida a la inhibición del ciclo de la urea, que contribuye a la morbimortalidad.…”

Section: Discussionunclassified

“…Además, un déficit secundario de carnitina genera la disminución en la energía y el estrés oxidativo se debe a la disminución de la capacidad antioxidante. 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.…”

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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Section: Discussionunclassified

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

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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“…Further examinations for PA revealed genetic mutations in the PCCA gene ( PCCA c.923dupT, PCCA c.229C > T), and the patient’s PCC enzymatic activity, quantified by ultra-high-performance liquid chromatography tandem mass spectrometry, was low (2.24%; Table 2 ). 9 After he was weaned-off the LVAD, bisoprolol was uptitrated from 2.5 to 15 mg to enhance his myocardial recovery. Angiotensin II receptor antagonists were also added for cardioprotection ( Figure 2 ).…”

Section: Case Presentationmentioning

confidence: 99%

Successful heart transplantation in a patient with adolescent-onset dilated cardiomyopathy secondary to propionic acidaemia: a case report

Seguchi

Toda

Hamada

et al. 2022

European Heart Journal - Case Reports

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Background Propionic acidemia (PA) is an autosomal recessive disorder resulting from deficiency of propionyl-CoA carboxylase (PCC), a mitochondrial enzyme that metabolizes propionyl-CoA. Generally, patients with PA develop symptoms in the neonatal period due to protein intake through breastfeeding; however, late-onset PA with atypical symptoms, including cardiomyopathy, has been recently reported. Case summary We present the case of a 25-year-old male with late-onset PA complicated by advanced heart failure (HF) due to isolated secondary dilated cardiomyopathy, who required left ventricular assist device (LVAD) implantation and finally underwent heart transplantation (HTx). Initially, the patient developed HF at the age of 16 and was diagnosed with mitochondrial cardiomyopathy. Due to refractory HF, he underwent an LVAD implantation and was scheduled for HTx. During the preoperative period for HTx, the patient suffered from sepsis due to the worsening of LVAD driveline exit-site infection complicated by overt metabolic acidosis, finally leading to the diagnosis of late-onset PA. After this diagnosis, adequate nutritional interventions were introduced, and the cardiac function was partially restored enough for him to be weaned off LVAD; however, the patient became inotrope-dependent and underwent HTx. The post-HTx course was uneventful with special nutritional management, and he has experienced no adverse metabolic events in the past three years. Discussion Late-onset PA can cause isolated adult-onset cardiomyopathy, and LVAD or HTx should be considered when PA is complicated by advanced HF and is unresponsive to conventional medical therapies.

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“…The pilot study and the following official screening program revealed an unexpectedly high frequency of PA due to a common variant PCCB p.Y435C. However, it has been difficult to conclude them as false positive subjects, for PCC activities in their lymphocytes were reported to be as low as 3–8% of normal control value [ 5 , 7 ]. Therefore, it is important to determine newborns who will need medical management, which will also reduce the burden of unnecessary anxiety and treatment for patients who will remain asymptomatic throughout life [ 8 ].…”

Section: Neonatal Screening For Pa In Japan: Issues To Be Addressedmentioning

confidence: 99%

Current Perspectives on Neonatal Screening for Propionic Acidemia in Japan: An Unexpectedly High Incidence of Patients with Mild Disease Caused by a Common PCCB Variant

Tanaka

Kagawa

Sakura

et al. 2021

IJNS

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Propionic acidemia (PA) is a disorder of organic acid metabolism which typically presents with acute encephalopathy-like symptoms associated with metabolic acidosis and hyperammonemia during the neonatal period. The estimated incidence of symptomatic PA in Japan is 1/400,000. The introduction of neonatal screening using tandem mass spectrometry has revealed a far higher disease frequency of approximately 1/45,000 live births due to a prevalent variant of c.1304T>C (p.Y435C) in PCCB, which codes β-subunit of propionyl-CoA carboxylase. Our questionnaire-based follow-up study reveals that most of these patients remain asymptomatic. However, reports on symptomatic patients exhibiting cardiac complications such as cardiomyopathy and QT prolongation have been increasing. Moreover, there were even cases in which these cardiac complications were the only symptoms related to PA. A currently ongoing study is investigating the risk of cardiac complications in patients with neonatal screening-detected PA caused by this common variant.

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Determination of methylmalonyl coenzyme A by ultra high-performance liquid chromatography tandem mass spectrometry for measuring propionyl coenzyme A carboxylase activity in patients with propionic acidemia

Cited by 3 publications

References 16 publications

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

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

Successful heart transplantation in a patient with adolescent-onset dilated cardiomyopathy secondary to propionic acidaemia: a case report

Current Perspectives on Neonatal Screening for Propionic Acidemia in Japan: An Unexpectedly High Incidence of Patients with Mild Disease Caused by a Common PCCB Variant

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