scholarly journals Brain Circuit Alterations and Cognitive Disability in Late-Onset Cobalamin D Disorder

2020 ◽  
Vol 9 (4) ◽  
pp. 990
Author(s):  
Javier De Las Heras ◽  
Ibai Diez ◽  
Antonio Jimenez-Marin ◽  
Alberto Cabrera ◽  
Daniela Ramos-Usuga ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Late Onset ◽  
Ventricular Volume ◽  
Methylmalonic Aciduria ◽  
Cognitive Disability ◽  
Clinical Genetic ◽  
Inborn Errors ◽  
Motor Tracts ◽  
Brain Circuit ◽  
Cobalamin Metabolism

Neuroimaging studies describing brain circuits’ alterations in cobalamin (vitamin B12)-deficient patients are limited and have not been carried out in patients with inborn errors of cobalamin metabolism. The objective of this study was to assess brain functionality and brain circuit alterations in a patient with an ultra-rare inborn error of cobalamin metabolism, methylmalonic aciduria, and homocystinuria due to cobalamin D disease, as compared with his twin sister as a healthy control (HC). We acquired magnetic resonance imaging (including structural, functional, and diffusion images) to calculate brain circuit abnormalities and combined these results with the scores after a comprehensive neuropsychological evaluation. As compared with HC, the patient had severe patterns of damage, such as a 254% increment of ventricular volume, pronounced subcortical and cortical atrophies (mainly at striatum, cingulate cortex, and precuneus), and connectivity alterations at fronto-striato-thalamic circuit, cerebellum, and corpus callosum. In agreement with brain circuit alterations, cognitive deficits existed in attention, executive function, inhibitory control, and mental flexibility. This is the first study that provides the clinical, genetic, neuroanatomical, neuropsychological, and psychosocial characterization of a patient with the cobalamin D disorder, showing functional alterations in central nervous system motor tracts, thalamus, cerebellum, and basal ganglia, that, as far as we know, have not been reported yet in vitamin B12-related disorders.

METHYLMALONIC ACID

PEDIATRICS ◽  
1973 ◽  
Vol 51 (6) ◽  
pp. 1012-1015
Author(s):  
Lewis A. Barness
Keyword(s):  
Vitamin B12 ◽  
Inborn Errors Of Metabolism ◽  
Methylmalonic Acid ◽  
Methylmalonic Aciduria ◽  
Organic Aciduria ◽  
Combined System ◽  
Inborn Errors ◽  
System Disease ◽  
Amino Aciduria

Methylmalonate studies have led to some understanding of vitamin B12 metabolism as well as certain inborn errors of metabolism. These, in turn, have served as models of a group of diseases related to acidosis, so that the study of organic aciduria at present is similar to that of amino aciduria 20 years ago. Techniques for studying these have been developed. Many unanswered questions remain. (1) What does methylmalonate do? Does it, itself, cause the acidosis? Does it cause a deficiency of succinate in the oxidative cycle? (2) Are more direct ways of increasing succinate available? (3) What is the relation of methylmalonate to combined system disease or vitamin B12 neuropathy? (4) Are enzymes defective or absent? (5) What is the significance of methylmalonate in the newborn? (6) How does one counsel or treat families which include members with methylmalonic aciduria?

Vitamin B12 Deficiency and West Syndrome: An Uncommon but Preventable Cause of Neurological Disorder. Report on Three Cases, One of Them with Late Onset during Vitamin B12 Treatment

2021 ◽  
Author(s):  
Piero Pavone ◽  
Federica Sullo ◽  
Raffaele Falsaperla ◽  
Filippo Greco ◽  
Agustina Crespo ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Late Onset ◽  
Vitamin B12 Deficiency ◽  
West Syndrome ◽  
Water Soluble ◽  
Vegan Diet ◽  
Inborn Errors ◽  
Water Soluble Vitamin ◽  
B12 Deficiency ◽  
Somatic Diseases

AbstractVitamin B12 is a water-soluble vitamin that plays a fundamental role as an essential cofactor for two enzymes responsible for the production of succinyl-CoA and methionine. Vitamin B12 deficiency can occur in infants and may be related to the breastfeeding mother's adherence to a vegan diet or somatic diseases in the mother. It should be differentiated from inborn errors of vitamin B12 metabolism. Herein, we report the cases of three infants with West syndrome; all three were breastfed by mothers who followed a strict vegan diet. In one of the three infants, West syndrome developed during treatment with vitamin B12 and normalization of the vitamin B12 level. Early treatment and replacement therapy are worthwhile to prevent serious neurological problems and to improve the patient's clinical course.

Mitochondrial vitamin B12-binding proteins in patients with inborn errors of cobalamin metabolism

2007 ◽  
Vol 90 (2) ◽  
pp. 140-147 ◽  
Author(s):  
E. Moras ◽  
A. Hosack ◽  
D. Watkins ◽  
D.S. Rosenblatt
Keyword(s):  
Vitamin B12 ◽  
Binding Proteins ◽  
Inborn Errors ◽  
Cobalamin Metabolism

scholarly journals PRDX1 gene-related epi-cblC disease is a common type of inborn error of cobalamin metabolism with mono- or bi-allelic MMACHC epimutations

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Catia Cavicchi ◽  
Abderrahim Oussalah ◽  
Silvia Falliano ◽  
Lorenzo Ferri ◽  
Alessia Gozzini ◽  
...  
Keyword(s):  
Genetic Variant ◽  
Clinical Phenotype ◽  
Antisense Transcription ◽  
Methylmalonic Aciduria ◽  
Metabolic Phenotype ◽  
Inborn Errors ◽  
Gene Testing ◽  
Genome Wide ◽  
Determining Factors ◽  
Cobalamin Metabolism

Abstract Background The role of epigenetics in inborn errors of metabolism (IEMs) is poorly investigated. Epigenetic changes can contribute to clinical heterogeneity of affected patients but could also be underestimated determining factors in the occurrence of IEMs. An epigenetic cause of IEMs has been recently described for the autosomal recessive methylmalonic aciduria and homocystinuria, cblC type (cblC disease), and it has been named epi-cblC. Epi-cblC has been reported in association with compound heterozygosity for a genetic variant and an epimutation at the MMACHC locus, which is secondary to a splicing variant (c.515-1G > T or c.515-2A > T) at the adjacent PRDX1 gene. Both these variants cause aberrant antisense transcription and cis-hypermethylation of the MMACHC gene promotor with subsequent silencing. Until now, only nine epi-cblC patients have been reported. Methods We report clinical/biochemical assessment, MMACHC/PRDX1 gene sequencing and genome-wide DNA methylation profiling in 11 cblC patients who had an inconclusive MMACHC gene testing. We also compare clinical phenotype of epi-cblC patients with that of canonical cblC patients. Results All patients turned out to have the epi-cblC disease. One patient had a bi-allelic MMACHC epimutation due to the homozygous PRDX1:c.515-1G > T variant transmitted by both parents. We found that the bi-allelic epimutation produces the complete silencing of MMACHC in the patient’s fibroblasts. The remaining ten patients had a mono-allelic MMACHC epimutation, due to the heterozygous PRDX1:c.515-1G > T, in association with a mono-allelic MMACHC genetic variant. Epi-cblC disease has accounted for about 13% of cblC cases diagnosed by newborn screening in the Tuscany and Umbria regions since November 2001. Comparative analysis showed that clinical phenotype of epi-cblC patients is similar to that of canonical cblC patients. Conclusions We provide evidence that epi-cblC is an underestimated cause of inborn errors of cobalamin metabolism and describe the first instance of epi-cblC due to a bi-allelic MMACHC epimutation. MMACHC epimutation/PRDX1 mutation analyses should be part of routine genetic testing for all patients presenting with a metabolic phenotype that combines methylmalonic aciduria and homocystinuria.

scholarly journals Current Nanocarrier Strategies Improve Vitamin B12 Pharmacokinetics, Ameliorate Patients’ Lives, and Reduce Costs

Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 743
Author(s):  
Marco Fidaleo ◽  
Stefano Tacconi ◽  
Carolina Sbarigia ◽  
Daniele Passeri ◽  
Marco Rossi ◽  
...  
Keyword(s):  
Side Effects ◽  
Vitamin B12 ◽  
Memory Performance ◽  
Oral Route ◽  
High Dose ◽  
Human Beings ◽  
Inborn Errors ◽  
Essential Nutrient

Vitamin B12 (VitB12) is a naturally occurring compound produced by microorganisms and an essential nutrient for humans. Several papers highlight the role of VitB12 deficiency in bone and heart health, depression, memory performance, fertility, embryo development, and cancer, while VitB12 treatment is crucial for survival in inborn errors of VitB12 metabolism. VitB12 is administrated through intramuscular injection, thus impacting the patients’ lifestyle, although it is known that oral administration may meet the specific requirement even in the case of malabsorption. Furthermore, the high-dose injection of VitB12 does not ensure a constant dosage, while the oral route allows only 1.2% of the vitamin to be absorbed in human beings. Nanocarriers are promising nanotechnology that can enable therapies to be improved, reducing side effects. Today, nanocarrier strategies applied at VitB12 delivery are at the initial phase and aim to simplify administration, reduce costs, improve pharmacokinetics, and ameliorate the quality of patients’ lives. The safety of nanotechnologies is still under investigation and few treatments involving nanocarriers have been approved, so far. Here, we highlight the role of VitB12 in human metabolism and diseases, and the issues linked to its molecule properties, and discuss how nanocarriers can improve the therapy and supplementation of the vitamin and reduce possible side effects and limits.

Rapid prenatal and postnatal detection of inborn errors of propionate, methylmalonate, and cobalamin metabolism: A sensitive assay using cultured cells

1976 ◽  
Vol 34 (3) ◽  
pp. 277-283 ◽  
Author(s):  
Huntington F. Willard ◽  
Lalit M. Ambani ◽  
Anita C. Hart ◽  
Maurice J. Mahoney ◽  
Leon E. Rosenberg
Keyword(s):  
Cultured Cells ◽  
Sensitive Assay ◽  
Inborn Errors ◽  
Cobalamin Metabolism

scholarly journals Eye movement disorders and neurological symptoms in late-onset inborn errors of metabolism

2018 ◽  
Vol 33 (12) ◽  
pp. 1844-1856 ◽  
Author(s):  
Lisette H. Koens ◽  
Marina A.J. Tijssen ◽  
Fiete Lange ◽  
Bruce H.R. Wolffenbuttel ◽  
Alessandra Rufa ◽  
...  
Keyword(s):  
Eye Movement ◽  
Movement Disorders ◽  
Inborn Errors Of Metabolism ◽  
Late Onset ◽  
Neurological Symptoms ◽  
Inborn Errors ◽  
Eye Movement Disorders

scholarly journals Influence of brain-derived neurotrophic factor and apolipoprotein E genetic variants on hemispheric and lateral ventricular volume of young healthy adults

2011 ◽  
Vol 23 (3) ◽  
pp. 132-138 ◽  
Author(s):  
Christos Sidiropoulos ◽  
Kourosh Jafari-Khouzani ◽  
Hamid Soltanian-Zadeh ◽  
Panayiotis Mitsias ◽  
Panagiotis Alexopoulos ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Neurotrophic Factor ◽  
Late Onset ◽  
Apoe Genotype ◽  
Ventricular Volume ◽  
Brain Derived Neurotrophic Factor ◽  
Healthy Adults ◽  
Ventricular Volumes ◽  
Neuronal Processes ◽  
Apoe Genotypes

Objective: Brain-derived neurotrophic factor (BDNF) and apolipoprotein E (ApoE) are thought to be implicated in a variety of neuronal processes, including cell growth, resilience to noxious stimuli and synaptic plasticity. A Val to Met substitution at codon 66 in the BDNF protein has been associated with a variety of neuropsychiatric conditions. The ApoE4 allele is considered a risk factor for late-onset Alzheimer's disease, but its effects on young adults are less clear. We sought to investigate the effects of those two polymorphisms on hemispheric and lateral ventricular volumes of young healthy adults.Methods: Hemispheric and lateral ventricular volumes of 144 healthy individuals, aged 19–35 years, were measured using high resolution magnetic resonance imaging and data were correlated with BDNF and ApoE genotypes.Results: There were no correlations between BDNF or ApoE genotype and hemispheric or lateral ventricular volumes.Conclusion: These findings indicate that it is unlikely that either the BDNF Val66Met or ApoE polymorphisms exert any significant effect on hemispheric or lateral ventricular volume. However, confounding epistatic genetic effects as well as relative insensitivity of the volumetric methods used cannot be ruled out. Further imaging analyses are warranted to better define any genetic influence of the BDNF Val6Met and ApoE polymorphism on brain structure of young healthy adults.

scholarly journals Vitamin B12-responsive neonatal megaloblastic anemia and homocystinuria with associated reduced methionine synthase activity

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1128-1133 ◽  
Author(s):  
LJ Hallam ◽  
M Sawyer ◽  
AC Clark ◽  
MB Van der Weyden
Keyword(s):  
Vitamin B12 ◽  
Developmental Delay ◽  
Genetic Heterogeneity ◽  
Megaloblastic Anemia ◽  
Methylmalonic Aciduria ◽  
Methionine Synthase ◽  
Cultured Fibroblasts ◽  
Neurologic Recovery ◽  
Neurologic Development ◽  
Growth Requirement

Abstract We present findings on an infant with neonatal megaloblastic anemia, homocystinuria, and neurologic dysfunction that included developmental delay and tonic seizures. There was no methylmalonic aciduria. Cyanocobalamin therapy was accompanied by complete hematologic and neurologic recovery, diminished homocystine excretion, and subsequently normal neurologic development. Cultured fibroblasts and lymphoblasts showed a reduced methionine synthase activity and a growth requirement for methionine. Cobalamin incorporation by the patient's lymphoblasts was normal, but the proportion of cellular methylcobalamin in the patient's lymphoblasts and fibroblasts were markedly reduced and that of adenosylcobalamin normal. The reduced methionine synthase activity was independent of assay reducing (thiol) conditions, but normal levels of activity accompanied culture of the patient's lymphoblasts in medium with markedly increased cobalamin concentration. The characteristics of the reduced methionine synthase of our patient differ significantly from that of the previously described infant with cobalamin E disease and suggest that genetic heterogeneity may characterize this mutation.

Sign in / Sign up

Export Citation Format

Share Document