Table of Contents

HK J Paediatr (New Series)
Vol 24. No. 1, 2019

HK J Paediatr (New Series) 2019;24:43-47

Case Report

The First Case of Cobalamin F Disorder in China: Report and Literature Review

F Tong, RL Yang, R Chen, ZY Zhao


Objectives: To investigate the phenotype, genotype and prognosis of cblF disorder (CblF). Methodology: Data including newborn screening and clinical features, LMBRD1 mutations, treatment and prognosis of the first CblF case in China and 17 reported CblF cases were collected and analysed. Results: This case was picked up by newborn screening (NBS) due to elevated blood propionylcarnitine (C3) (5.50 μmol/L), propionylcarnitine / acetylcarnitine (C3/C2) ratio (0.47), propionylcarnitine / free carnitine C3/C0 ratio (0.25) and decreased methionine (Met) (5.27 μmol/L) identified by tandem mass spectrometry (MS-MS), then decreased serum Vitamin B12 (cobalamin; Vit B12) (116 pmol/L), elevated homocysteine (tHCY) (82.9 μmol/L), macrocytic anaemia and atrial septal defect, and patent ductus arteriosus were confirmed. This is similar to what has been reported in the literature. Besides, two novel truncated LMBRD1 mutations of p.R277* and p.C29* were confirmed. The data of all the 18 cases show that the common clinical features are macrocytic anaemia, failure to thrive, developmental delay, congenital heart disease, and small for gestational age. Similar biochemical characters were identified in all 3 cases from NBS, and a total of 35 LMBRD1 mutations in 10 different sites including frame-shift mutations (30/35), splice site mutations (2/35), nonsense mutations (2/35), and large fragment deletions (1/35) were observed, among which c.1056delG mutation was reported the most frequently (24/35). After Vit B12 injection and supportive treatment, all of the biochemical abnormalities and most of the clinical presentations have been significantly improved within 3 months in all cases. Conclusion: The biochemical characters of CblF are similar to the combined methylmalonic acid (MMA), except for decreased serum Vit B12, which should be distinguished from Vit B12 deficiency. Typical phenotype includes macrocytic anaemia, growth and development problems, and congenital malformations, all of which are nonspecific. The c.1056delG mutation is the common mutation. The concentrations of C3, C3/C2, C3/C0 and Met by MS-MS and the target genetic panel of MMA should be chosen for suspected MMA cases. CblF is a treatable disease, and injection of Vit B12 is effective, but the appropriate dosage remains unclear.

Keyword : Cobalamin; Genotype; Phenotype; Prognosis; Treatment

Abstract in Chinese


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