Long-term effectiveness of carglumic acid in patients with propionic acidemia (PA) and methylmalonic acidemia (MMA): a randomized clinical trial.

Wafaa Eyaid, Ali Alasmari, Zuhair Rahbeeni, Mohamed A Hussein, Bayan Albdah, Majed Aljeraisy, Mohammed Almannai, Eissa Faqeih, Lina Alohali, Abdulrahman Alswaid, Majid Alfadhel, Fuad Al Mutairi, Faroug Ababneh, Hind Ahmed, Muhammad Umair, Ali Al Othaim, Ahmed Alfares, Mohammed Elamin, Mohammed Saleh, Marwan Nashabat

Journal: Orphanet journal of rare diseases 2021;16(1):422

PMID: 34635114

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Abstract

BACKGROUND

Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare, autosomal recessive inborn errors of metabolism that require life-long medical treatment. The trial aimed to evaluate the effectiveness of the administration of carglumic acid with the standard treatment compared to the standard treatment alone in the management of these organic acidemias.

METHODS

The study was a prospective, multicenter, randomized, parallel-group, open-label, controlled clinical trial. Patients aged ≤ 15 years with confirmed PA and MMA were included in the study. Patients were followed up for two years. The primary outcome was the number of emergency room (ER) admissions because of hyperammonemia. Secondary outcomes included plasma ammonia levels over time, time to the first episode of hyperammonemia, biomarkers, and differences in the duration of hospital stay.

RESULTS

Thirty-eight patients were included in the study. On the primary efficacy endpoint, a mean of 6.31 ER admissions was observed for the carglumic acid arm, compared with 12.76 for standard treatment, with a significant difference between the groups (p = 0.0095). Of the secondary outcomes, the only significant differences were in glycine and free carnitine levels.

CONCLUSION

Using carglumic acid in addition to standard treatment over the long term significantly reduces the number of ER admissions because of hyperammonemia in patients with PA and MMA.

Address: Genetics and Precision Medicine department (GPM), King Abdullah Specialized Children's Hospital (KASCH), King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences (KSAUHS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia. [email protected].; Genetics and Precision Medicine department (GPM), King Abdullah Specialized Children's Hospital (KASCH), King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences (KSAUHS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.; Medical Genetics Section, King Fahad Medical City, Children's Hospital, Riyadh, Kingdom of Saudi Arabia.; Department of Pediatrics, College of Medicine, Qassim University, Buraidah, Kingdom of Saudi Arabia.; Department of Pathology, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Science, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (NGHA), Riyadh, Kingdom of Saudi Arabia.; Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences, King AbdulAziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia.; King Abdullah International Medical Research Centre, College of Pharmacy, King Saud bin Abdulaziz University for Health Science, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Kingdom of Saudi Arabia.; Department Biostatistics and Bioinformatics, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Science, Ministry of National Guard-Health Affairs, Riyadh, Kingdom of Saudi Arabia.; Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia.

DOI: 10.1186/s13023-021-02032-8

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MeSH Terms: Amino Acid Metabolism, Inborn Errors, Glutamates, Humans, Methylmalonic Acid, Propionic Acidemia, Prospective Studies