Emerging trends in management of propionic acidemia

http://dx.doi.org/10.1590/0004-2730000002821 original article Emerging trends in management of propionic acidemia Tendências emergentes no manejo da academia propiônica Muhammad Rafique1 ABSTRACT Objetivo: To evaluate the therapeutic agents used during metabolic crises and in long-term management of patients with propionic acidemia (PA). Materials and methods: The records of PA patients were retrospectively evaluated. Results: The study group consisted of 30 patients with 141 admissions. During metabolic crises, hyperammonemia was found in 130 (92%) admissions and almost all patients were managed with normal saline, ≥ 10% dextrose, and restriction of protein intake. In 56 (40%) admissions, management was done in intensive care unit, 31 (22%) with mechanical ventilation, 10 (7%) with haemodialysis, 16 (11%) with vasopressor agents, and 12 (9%) with insulin. In the rescue procedure, L-carnitine was used in 135 (96%) patients, sodium bicarbonate in 116 (82%), sodium benzoate in 76 (54%), and metronidazole in 10 (7%), biotin in about one-quarter, L-arginine in one third, and antibiotics in three-quarter of the admissions. Blood/packed RBCs were used in 28 (20%) patients, platelets in 26 (18%), fresh frozen plasma in 8 (6%), and granulocyte-colony stimulating factors in 10 (7%) admissions. All patients were managed completely/partially with medical nutrition formula plus amino acid mixture, vitamins and minerals. For long-term management 24 (80%) patients were on L-carnitine, 22 (73%) on sodium benzoate, 6 (20%) on biotin, one half on alkaline therapy and 4 (13%) on regular metronidazole use. Almost all patients were on medical formula and regular follow-up. Conclusion: Aggressive and adequate management of acute metabolic crises with restriction of protein intake, stabilization of patient, reversal of catabolism, and removal of toxic metabolites are essential steps. Concerted efforts to ensure adequate nutrition, to minimize the risk of acute decompensation and additional therapeutic advances are imperative to improve the outcome of PA patients. Arq Bras Endocrinol Metab. 2014;58(3):237-42 1 Central Aseer Hospital Abha, Kingdom of Saudi Arabia Keywords Propionate; therapeutic agents; management; latest trends; metabolic crises; hyperammonaemia RESUMO Correspondence to: Muhammad Rafique Associate Professor, Department of Paediatrics, Fatima Jinnah Medical College, University of Health Sciences Lahore, Pakistan Received on May/23/2013 Accepted on Jan/24/2014 Copyright© ABE&M todos os direitos reservados. Objetivo: Avaliar os agentes terapêuticos usados durante as crises metabólicas e para o manejo de longo prazo de pacientes com academia propiônica (AP). Materiais e métodos: Avaliação retrospectiva das fichas médicas de pacientes com AP. Resultados: O grupo estudado consistiu de 30 pacientes com 141 hospitalizações. Durante as crises metabólicas, a hiperamonemia foi observada em 130 (92%) pacientes hospitalizados e quase todos foram tratados com solução salina regular, ≥ 10% dextrose e restrição da ingestão de proteína. Em 56 (40%) das hospitalizações, o manejo foi feito na unidade de terapia intensiva, 31(22%) com ventilação mecânica, 10 (7%) com hemodiálise, 16 (11%) com vasopressores e 12 (9%) com insulina. Para o resgate, a L-carnitina foi usada em 135 (96%) pacientes, o bicarbonato de sódio em 116 (82%), o benzoato de sódio em 76 (54%), o metronidazole em 10 (7%), a biotina em cerca de um quarto, a L-arginina em um quarto e antibióticos em três quartos dos pacientes hospitalizados. Sangue/concentrado de hemácias foram usados em 28 (20%), plaquetas em 26 (18%), plasma fresco congelado em 8 (6%) e fatores estimulantes de colônias de granulócitos em 10 (7%) pacientes hospitalizados. Todos os pacientes foram manejados completamente/parcialmente com fórmula de nutrição hospitalar mais uma mistura de aminoácidos, vitaminas e minerais. Para o manejo de longo prazo, 24 (80%) dos pacientes foram tratados com L-carnitina, 22 (73%) com benzoato de sódio, 6 (20%) com biotina, a metade com tratamento alcalino e 4 (13%) com uso regular de metronidazole. Quase todos os pacientes foram tratados com fórmulas médicas e acompanhamento regular. Conclusão: O manejo adequado e agressivo de crises metabólicas com restrição da ingestão de proteína, estabilização do pacientes e reversão do catabolismo, e remoção dos metabólitos tóxicos são passos essenciais. Esforços concentrados para garantir a nutrição adequada, minimizar o risco de descompensação aguda e avanços terapêuticos adicionais são imperativos na melhora dos desfechos de pacientes com AP. Arq Bras Endocrinol Metab. 2014;58(3):237-42 Descritores Propionato; agentes terapêuticos; manejo; últimas tendências; crises metabólicas; hiperamonemia Arq Bras Endocrinol Metab. 2014;58/3 237 Management of propionic acidemia INTRODUCTION P Copyright© ABE&M todos os direitos reservados. ropionic acidemia (PA) is a rare metabolic disorder, caused by deficiency of a mitochondrial enzyme propionyl CoA carboxylase (PCC) resulting in accumulation of highly toxic metabolites. The disorder is unusually frequent in Saudi Arabia, and has been reported to occur in 1 in 2,000 to 1 in 5,000 live births in this region (1). About 80% PA patients are early-onset cases (diagnosed < 3 months of age). They have more severe disease and classically present, in the neonatal period, lethargy, vomiting, refusal to feed, hypotonia and, less frequently, dehydration and seizures. Some patients have late-onset disease (manifested any time after three months of age), show milder symptoms, and long survival rate. PA is usually associated with long-term neurological complications and is characterized by recurrent episodes of metabolic crises (2). Several metabolites and physiological stressors are thought to account for many of the acute and chronic disease manifestations. Common findings include metabolic acidosis, ketosis, hyperammonemia, increased incidence of infections and bone marrow suppression. During metabolic crises, total protein restriction, reversal of catabolism and rapid detoxification are essential life-saving steps to prevent acute brain injury, severe morbidity and mortality (2). Treatment options include low protein diet, carnitine, biotin, a precursor free amino acid formula and alkaline therapy. Hemodiafilteration/hemodialysis is recommended for severe hyperammonemia, extreme acidosis, and dangerous electrolyte imbalance (3). Packed red blood cells (RBCs) transfusion and/or granulocyte colony stimulating factors (G-CSF) are recommended in anemia, neutropenia, or bone marrow suppression (2). Antibiotics are commonly used during metabolic crises, which have strong association with immuno-suppression and sepsis (1). The objective of this study was to evaluate the therapeutic agents used for acute management during metabolic crisis and those used on a regular basis for long term management of the PA patients to minimize the risk of recurrent me (...truncated)