Cobalamin C defect is caused by pathogenic variants in the MMACHC gene leading to impaired conversion of dietary vitamin B into methylcobalamin and adenosylcobalamin. Variants in the MMACHC gene cause accumulation of methylmalonic acid and homocysteine along with decreased methionine synthesis. The spectrum of MMACHC gene variants differs in various populations. A total of 19 North Indian children (age 0-18 years) with elevated methylmalonic acid and homocysteine were included in the study, and their DNA samples were subjected to Sanger sequencing of coding exons with flanking intronic regions of MMACHC gene. The genetic analysis resulted in the identification of a common pathogenic nonsense mutation, c.394C > T (R132*) in 85.7% of the unrelated cases with suspected cobalamin C defect. Two other known mutations c.347T > C (7%) and c.316G > A were also detected. Plasma homocysteine was significantly elevated (> 100 µmol/L) in 75% of the cases and methionine was decreased in 81% of the cases. Propionyl (C3)-carnitine, the primary marker for cobalamin C defect, was found to be elevated in only 43.75% of cases. However, the secondary markers such as C3/C2 and C3/C16 ratios were elevated in 87.5% and 100% of the cases, respectively. Neurological manifestations were the most common in our cohort. Our findings of the high frequency of a single MMACHC R132* mutation in cases with combined homocystinuria and methylmalonic aciduria may be proven helpful in designing a cost-effective and time-saving diagnostic strategy for resource-constraint settings. Since the R132* mutation is located near the last exon-exon junction, this is a potential target for the read-through therapeutics.
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http://dx.doi.org/10.1007/s00726-021-02942-8 | DOI Listing |
J Med Case Rep
December 2024
Faculty of Medicine, Al-Quds University, Jerusalem, Palestine.
Background: Evans syndrome is a rare disorder characterized by the simultaneous or sequential combination of autoimmune hemolytic anemia and immunological thrombocytopenia, together with a positive direct antiglobulin test. This syndrome, which can be primary or secondary, is a rare initial manifestation of autoimmune diseases, notably systemic lupus erythematosus, with 1.7-2.
View Article and Find Full Text PDFDifferentiation
December 2024
Department of Biological Sciences, University of Texas El Paso, 500 W. University Ave 79968, El Paso, TX, USA. Electronic address:
Vitamin B, otherwise known as cobalamin, is an essential water-soluble vitamin that is obtained from animal derived dietary sources. Mutations in the genes that encode proteins responsible for cobalamin uptake, transport, or processing cause inborn errors of cobalamin metabolism, a group of disorders characterized by accumulation of homocysteine and methylmalonic acid, neurodevelopmental defects, ocular dysfunction, anemia, and failure to thrive. Mild to moderate craniofacial phenotypes have been observed but these phenotypes are not completely penetrant and have not been consistently recognized in the literature.
View Article and Find Full Text PDFBMC Pediatr
December 2024
Shiraz Transplant Research Center (STRC), Shiraz University of Medical Sciences, Shiraz, Iran.
Objective: Methylmalonic acidemia (MMAs) is known as a severe, complex, and lethal disorder of methylmalonate and cobalamin. The patients with MMA may have developmental, neurological, and metabolic disorders such as liver disease. Here, we aim to evaluate 6 Iranian patients suspected to MMA disorder.
View Article and Find Full Text PDFMol Genet Metab Rep
December 2024
Biochemical Genetics Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Methylmalonic aciduria and homocystinuria, CblC type, is an inborn error of intracellular vitamin B12 (cobalamin) metabolism caused, in the majority of cases, by mutations in the gene. Five Cypriot patients (four males and one female) were diagnosed with a CblC defect. Age at diagnosis ranged from 10 days to 9 months.
View Article and Find Full Text PDFAm J Ophthalmol Case Rep
December 2024
Mitchel and Shannon Wong Eye Institute, Department of Ophthalmology, Dell Medical School at the University of Texas at Austin, Austin, TX, USA.
Purpose: To highlight the utility of ganglion cell layer (GCL) analysis in early diagnosis of optic neuropathy secondary to copper deficiency and emphasize the importance of timely repletion for visual recovery.
Observations: A 67-year-old woman presented with four months of gradually decreasing vision bilaterally. Medical history was significant for Stage I duodenal and Stage III colon cancer treated with Whipple surgery and hemicolectomy.
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