The Application of Clinical Genetics (Jun 2025)
Intramuscular Vitamin B12 Treatment in Transcobalamin II Deficiency: Case Series Clinical Outcomes
Abstract
Ali M Sawlan,1 Msaed Alotaibi,1 Rayan M Alharbi,1 Nimr A Alwahbi,1 Manar Alshammary,2 Ali Mohammad Alasmari,2 Fuad Al Mutairi3,4 1College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia; 2Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia; 3Genetic and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia; 4King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi ArabiaCorrespondence: Fuad Al Mutairi, Genetic and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), P. O. Box 22490, Riyadh, 11426, Saudi Arabia, Tel +966-11-8011111 Ext. 53561, Fax +966-11-8011111 Ext. 53555, Email [email protected]: Transcobalamin II (TC II) deficiency is a rare autosomal recessive disorder that typically manifests in early infancy. Symptoms include failure to thrive, vomiting, weakness, and pancytopenia. If left undiagnosed and untreated, it can be life-threatening. TC II is crucial for transporting cobalamin (vitamin B12), which plays a vital role in homocysteine and methylmalonic acid metabolism. It serves as a cofactor in neurotransmitter synthesis and protein methylation processes.Methods: In this study, we reviewed the clinical presentation, treatment approaches, and long-term outcomes of four patients with confirmed TC II deficiency. All subjects were born to consanguineous parents and exhibited symptoms between birth and four months of age.Results: All patients presented with hematological abnormalities, elevated methylmalonic acid (MMA), and increased total homocysteine (tHcy) levels. Whole Exome Sequencing (WES) confirmed TC II deficiency in all cases, revealing diverse mutation spectra, primarily frameshift mutations (leu320Valfs*51, and IIe330Hisfs*9). No clear genotype-phenotype correlations were observed. The majority of patients were treated with intramuscular hydroxocobalamin (OH-Cbl), resulting in clinical and biochemical improvements.Conclusion: This study underscores the importance of early detection and appropriate management of TC II deficiency to prevent permanent morbidity and potentially fatal outcomes. Regular monitoring of clinical and neurological status, as well as MMA and tHcy levels, is essential to ensure adequate therapy. Intramuscular treatment is the preferred route to prevent neurological deficits and optimal markers normalization.Keywords: cobalamin, Cbl, vitamin B12, transcobalamin II, hydroxocobalamin, OH-Cbl
