In vivo andin vitro responsiveness to vitamin B12 in a case of methylmalonic aciduria

1982 ◽  
Vol 5 (S1) ◽  
pp. 35-36 ◽  
Author(s):  
A. Green ◽  
J. A. Black ◽  
A. J. Francis ◽  
R. G. F. Gray
Keyword(s):  
Vitamin B12 ◽  
Methylmalonic Aciduria

scholarly journals Genetic testing is necessary for correct diagnosis and treatment in patients with isolated methylmalonic aciduria: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Katarína Brennerová ◽  
Martina Škopková ◽  
Mária Ostrožlíková ◽  
Jana Šaligová ◽  
Juraj Staník ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Clinical Symptoms ◽  
Oral Treatment ◽  
Correct Diagnosis ◽  
Methylmalonic Aciduria ◽  
Intensive Treatment ◽  
Genetic Tests

Abstract Background Isolated methylmalonic aciduria can be caused by pathogenic mutations in the gene for methylmalonyl-CoA mutase or in the genes encoding enzymes involved in the intracellular metabolism of cobalamin. Some of these mutations may be cobalamin responsive. The type of methylmalonic aciduria cannot always be assumed from clinical manifestation and the responsiveness to cobalamin has to be assessed for appropriate cobalamin administration, or to avoid unnecessary treatment. The cases presented herein highlight the importance of genetic testing in methylmalonic aciduria cases and the need for standardisation of the in vivo cobalamin-responsiveness assessment. Case presentation We describe two patients who presented in the first week of life with rapid neurological deterioration caused by metabolic acidosis with severe hyperammonaemia requiring extracorporeal elimination in addition to protein restriction, energy support, carnitine, and vitamin B12 treatment. The severity of the clinical symptoms and high methylmalonic acid concentrations in the urine (>30,000 μmol/mmol of creatinine) without hyperhomocysteinaemia in both of our patients suggested isolated methylmalonic aciduria. Based on the neonatal manifestation and the high methylmalonic acid urine levels, we assumed the cobalamin non-responsive form. The in vivo test of responsiveness to cobalamin was performed in both patients. Patient 1 was evaluated as non-responsive; thus, intensive treatment with vitamin B12 was not used. Patient 2 was responsive to cobalamin, but the dose was decreased to 1 mg i.m. every two weeks with daily oral treatment due to non-compliance. Genetic tests revealed bi-allelic mutations in the genes MMAB and MMAA in Patient 1 and 2, respectively. Based on these results, we were able to start intensive treatment with hydroxocobalamin in both patients. After the treatment intensification, there was no acute crisis requiring hospitalisation in Patient 1, and the urine methylmalonic acid levels further decreased in Patient 2. Conclusions Despite carrying out the in vivo test of responsiveness to cobalamin in both patients, only the results of molecular genetic tests led us to the correct diagnosis and enabled intensive treatment with hydroxocobalamin. The combination of the standardized in vivo test of cobalamin responsiveness and genetic testing is needed for accurate diagnosis and appropriate treatment of isolated methylmalonic aciduria.

Bioavailability of Vitamin B12

2010 ◽  
Vol 80 (45) ◽  
pp. 330-335 ◽  
Author(s):  
Lindsay Helen Allen
Keyword(s):  
Vitamin B12 ◽  
Vitamin B12 Deficiency ◽  
The Elderly ◽  
Radioactive Isotopes ◽  
Animal Source Foods ◽  
Dietary Requirements ◽  
In Vivo Labeling ◽  
B12 Deficiency ◽  
Vitamin B12 Malabsorption

Vitamin B12 deficiency is common in people of all ages who consume a low intake of animal-source foods, including populations in developing countries. It is also prevalent among the elderly, even in wealthier countries, due to their malabsorption of B12 from food. Several methods have been applied to diagnose vitamin B12 malabsorption, including Schilling’s test, which is now used rarely, but these do not quantify percent bioavailability. Most of the information on B12 bioavailability from foods was collected 40 to 50 years ago, using radioactive isotopes of cobalt to label the corrinoid ring. The data are sparse, and the level of radioactivity required for in vivo labeling of animal tissues can be prohibitive. A newer method under development uses a low dose of radioactivity as 14C-labeled B12, with measurement of the isotope excreted in urine and feces by accelerator mass spectrometry. This test has revealed that the unabsorbed vitamin is degraded in the intestine. The percent bioavailability is inversely proportional to the dose consumed due to saturation of the active absorption process, even within the range of usual intake from foods. This has important implications for the assessment and interpretation of bioavailability values, setting dietary requirements, and interpreting relationships between intake and status of the vitamin.

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.

Acrodermatitis-Like Syndrome in Organic Aciduria

PEDIATRICS ◽  
1994 ◽  
Vol 93 (3) ◽  
pp. 537-537
Author(s):  
U. Blecker ◽  
Y. Vandenplas ◽  
L. De Meirleir ◽  
L. De Raeve ◽  
J. Ramet
Keyword(s):  
Vitamin B12 ◽  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Methylmalonic Aciduria ◽  
Organic Aciduria ◽  
Asymptomatic Patients ◽  
High Doses

Methylmalonic aciduria (MMA) is an autosomal recessive in-born error of metabolism with a variation in the severity of the clinical manifestations, ranging from asymptomatic patients to fulminating neonatal forms causing severe ketosis, acidosis, hyperammonemia, pancytopenia, coma, and death. Severe cases can be treated with high doses of vitamin B12 and a diet low in proteins. We describe an exceptional manifestation of MMA. A 14-month-old boy with a neonatal manifestation of MMA was admitted during an intercurrent infection with ketoacidosis and hypoglycemia.

scholarly journals Stimulation in vitro of vitamin B12-dependent methionine synthase by polyamines

1996 ◽  
Vol 316 (2) ◽  
pp. 661-665 ◽  
Author(s):  
Susan H. KENYON ◽  
Anna NICOLAOU ◽  
Tamara AST ◽  
William A. GIBBONS
Keyword(s):  
Enzyme Activity ◽  
Vitamin B12 ◽  
Cell Signalling ◽  
Methionine Synthase ◽  
Polyamine Metabolism ◽  
Physiological Concentration ◽  
Methylation Pathway ◽  
Important Enzyme

Vitamin B12-dependent methionine synthase is an important enzyme for sulphur amino acid, folate polyamine metabolism, S-adenosylmethionine metabolism and also in the methylation pathway of DNA, RNA, proteins and lipids. Consequently, studies aiming at exploring the control and regulation of methionine synthase are of particular interest. Here we report the modulation of enzyme activity in vitro by polyamines. Although putrescine, cadaverine, spermine and spermidine all stimulated enzyme activity, the last two were the most potent, causing increases in enzyme activity up to 400%. The EC50 for spermine was determined as 8 μM and for spermidine 40 μM. The physiological concentration for spermine has been reported to be 15–19 μM. Spermine was found to increase both the Km and the Vmax with respect to methyltetrahydrofolate for the enzyme. These data support the hypothesis that spermine and spermidine are feedback regulators of methionine synthase both in vivo and in vitro and are consistent with the polyamines' regulating cell signalling pathways.

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