ABSTRACT
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.
Propionic acidemia is an infrequent disorder with an autosomal recessive inheritance pattern caused by the deficiency of the mitochondrial enzyme propionyl-CoA carboxylase that converts propionyl-CoA to D-methylmalonyl-CoA. We present the case of a male newborn who showed signs of respiratory distress, vomiting and tiredness during feeding. He presented metabolic acidosis, positive serum and urine ketone bodies, hyperammonemia, anemia, thrombocytopenia and hypoproteinemia. The biochemical study by gas chromatography coupled to mass spectrometry in a urine sample was suggestive of propionic acidemia. The molecular study in the PCCA gene found the mutations c.893A>G (p.K298R) in the father and c.937C> T (p.R313X) in the mother. There is a need to establish the diagnosis of this infrequent entity to implement the therapeutic measures available and provide the appropriate genetic counseling.
Subject(s)
Humans , Male , Infant, Newborn , Inheritance Patterns , Methylmalonyl-CoA Decarboxylase , Propionic Acidemia , Genetic CounselingABSTRACT
Subject(s)
Child , Child, Preschool , Humans , Abdominal Pain , Acidosis , Diagnosis , Diethylpropion , Hyperammonemia , Inpatients , Metabolic Diseases , Methylmalonyl-CoA Decarboxylase , Molecular Biology , Muscle Hypotonia , Pancreatitis , Parenteral Nutrition, Total , Propionic Acidemia , Seizures , Shock , VomitingABSTRACT
<p><b>OBJECTIVE</b>To analyze PCCA and PCCB gene mutations in 10 Chinese patients with propionic acidemia(PA).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood leukocytes. The 39 exons and flanking sequences of the PCCA and PCCB genes were amplified with polymerase chain reaction and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>DNA sequencing has revealed that 7 patients have carried a PCCA gene mutation, 2 patients carried PCCB gene mutation and 1 patient carried mutations in both PCCA and PCCB genes. Ten PA mutations were confirmed, including 8 affecting the PCCA gene and 2 affecting the PCCB gene. Three PCCA mutations c.245G>A, IVS15+5del5, c.1288C>T and 2 PCCB mutations c.838insC, c.1087T>C were found for the first time.</p><p><b>CONCLUSION</b>Among Chinese patients with propionic acidemia patients, their genetic mutations are mainly found on the PCCA gene.</p>
Subject(s)
Child, Preschool , Female , Humans , Infant , Male , Methylmalonyl-CoA Decarboxylase , Genetics , Mutation , Propionic Acidemia , GeneticsABSTRACT
Propionic acidemia (PA) is a rare autosomal recessive disorder of metabolism caused by deficient activity of the mitochondrial enzyme propionyl-CoA carboxylase. The clinical manifestations are metabolic acidosis, poor feeding, lethargy, vomiting, osteoporosis, neurological dysfunction, pancytopenia, developmental retardation and cardiomyopathy. Liver transplantation has recently been considered as one of the treatment options for patients with PA. This case report describes several anesthetic considerations for patients with PA undergoing liver transplantation. Understanding the patient's status and avoiding events that may precipitate metabolic acidosis are important for anesthetic management of patients with PA. In conclusion, anesthesia should be focused on minimizing the severity of metabolic acidosis with following considerations: (1) maintaining optimal tissue perfusion by avoiding hypotension, (2) preventing hypoglycemia, and (3) providing bicarbonate to compensate for the acidosis.
Subject(s)
Child , Humans , Acidosis , Acyl Coenzyme A , Anesthesia , Cardiomyopathies , Diethylpropion , Hypoglycemia , Hypotension , Lethargy , Liver , Liver Transplantation , Methylmalonyl-CoA Decarboxylase , Osteoporosis , Pancytopenia , Perfusion , Propionic Acidemia , VomitingABSTRACT
Paciente pretérmino que reingresa a la unidad de recién nacidos de la Clínica Universitaria Colombia, Bogotá DC, por problemas en la alimentación y pobre ganancia ponderal, a quien se le diagnosticó acidemia propiónica mediante cromatografía de ácidos orgánicos en orina. Los errores innatos del metabolismo son entidades que a pesar de tener una baja incidencia, se deben considerar en todo neonato con encefalopatía, problemas en la alimentación o pobre ganancia ponderal, entre otras manifestaciones, ya que el diagnóstico temprano y tratamiento oportuno previenen la aparición de secuelas neurológicas con retardo del desarrollo psicomotor y muerte temprana.
Preterm infant readmitted to the neonatal unit at ClínicaUniversitaria Colombia, Bogotá DC, presenting poor feeding and delays in normal growth velocity, who was diagnosed with propionic acidemiaby means of a urine organic acid profiling by chromatography. Although its low incidence, inborn metabolic disorders must be considered in any newborn presenting with encefalopathy, poor feeding or delays in normal growth velocity, among other manifestations for early diagnosisandprompt treatment preventneurological sequellae including psychomotor retardation and early neonatal death.
Subject(s)
Infant, Newborn , Propionic Acidemia/diagnosis , Infant, Newborn, Diseases , Hyperammonemia , Methylmalonyl-CoA DecarboxylaseABSTRACT
<p><b>OBJECTIVE</b>Propionic acidemia is a common organic acidemia, caused by deficiency of propionyl-CoA carboxylase (PCC), which catalyzes the carboxylation of propionyl-CoA to D-methylmalonyl-CoA. PCC is a dodecameric enzyme of alpha-PCC and beta-PCC subunits, nuclearly encoded by genes PCCA and PCCB, respectively. Mutation in either gene cause propionic acidemia, the PCCA gene is located on chromosome 13q32 with 24 exons and the PCCB gene is located on chromosome 3q13.2-q22 with 15 exons. In this study, we analyzed gene mutations of 11 PCCA and PCCB deficient patients from China and to explore the possible mutation spectrum.</p><p><b>METHODS</b>All 39 exons of PCCA and PCCB genes in 11 unrelated Chinese PA patients were analyzed by polymerase chain reaction (PCR) and direct sequencing. Genomic DNA was extracted using phenol-chloroform method from the peripheral blood leukocytes of each patient. PCR amplification products were checked by 1.8% agarose gel electrophoresis and were subsequently sequenced with ABI 3700 Automated DNA Sequencer.</p><p><b>RESULTS</b>The authors identified 13 PA mutations, 8 affecting the PCCA gene, 5 affecting the PCCB gene, including 10 novel mutations and 3 previously reported mutations. Three missense mutations (1079T > G, 1102G > C and 1850T > C), one splicing mutation (716-2A > G) and one short deletion (1863delA) were found in alpha-PCC subunit while three missense mutations (484G > A, 601G > A and 1253C > T) and two short insertion-deletions (167-179del13ins1, 560-561delCCinsT) were found in beta-PCC subunit. The 167-179del13ins1 change was identified in two homozygous PA patients, with allelic frequency of 40% in beta-PCC subunit deficiencies.</p><p><b>CONCLUSION</b>Thirteen mutations were found in 11 Chinese PA patients including ten novel mutations. No mutation is predominant in Chinese PCCA and PCCB deficient patients.</p>
Subject(s)
Humans , Infant , Infant, Newborn , Base Sequence , DNA Mutational Analysis , Exons , Methylmalonyl-CoA Decarboxylase , Genetics , Molecular Sequence Data , Mutation , Propionic Acidemia , Genetics , Sequence DeletionABSTRACT
Propionic acidemia is an autosomal-recessive inborn error of branched-chain amino acid metabolism. It is caused by deficient activity of propionyl-coenzyme A carboxylase and is characterized by a spectrum of clinical and biochemical findings. It usually manifests in the neonatal period or early infancy. Since Childs et al first described the propionic acidemia of infants in 1961, it has rarely been reported. There have been no previous report of this organic acidemia in Korea. We present a case of propionic acidemia in a 4-day old male, who had poor feeding, dehydration, and hyperammonemia and died at 12 days of age. Diagnosis was established by gas chromatography and mass spectrometry, and this case is the first reported propionic acidemia in literature in Korea. A review of the related literature was included.
Subject(s)
Child , Humans , Infant , Male , Chromatography, Gas , Dehydration , Diagnosis , Diethylpropion , Hyperammonemia , Korea , Mass Spectrometry , Metabolism , Methylmalonyl-CoA Decarboxylase , Propionic AcidemiaABSTRACT
Propionic acidemia is an autosomal-recessive inborn error of branched-chain amino acid metabolism. It is caused by deficient activity of propionyl-coenzyme A carboxylase and is characterized by a spectrum of clinical and biochemical findings. It usually manifests in the neonatal period or early infancy. Since Childs et al first described the propionic acidemia of infants in 1961, it has rarely been reported. There have been no previous report of this organic acidemia in Korea. We present a case of propionic acidemia in a 4-day old male, who had poor feeding, dehydration, and hyperammonemia and died at 12 days of age. Diagnosis was established by gas chromatography and mass spectrometry, and this case is the first reported propionic acidemia in literature in Korea. A review of the related literature was included.