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?

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.

Prenatal Diagnosis of Methylmalonic Aciduria

PEDIATRICS ◽  
1974 ◽  
Vol 54 (4) ◽  
pp. 511-513
Author(s):  
D. Gompertz ◽  
Patricia A. Goodey ◽  
J. M. Saudubray ◽  
Christiane Charpentier ◽  
Agnes Chignolle ◽  
...  
Keyword(s):  
At Risk ◽  
Prenatal Diagnosis ◽  
Amniotic Fluid ◽  
Methylmalonic Acid ◽  
Methylmalonic Aciduria ◽  
Postnatal Period ◽  
Small Molecular Weight ◽  
Inborn Errors ◽  
Abnormal Accumulation ◽  
Amniotic Cell

The abnormal accumulation of small molecular weight metabolites in amniotic fluid in inborn errors of metabolism is unusual and prenatal diagnosis usually requires amniotic cell culture and specific enzyme assay. However, Morrow et al.1 reported raised concentrations of methylmalonic acid in the amniotic fluid of a pregnancy at risk from methylmalonic aciduria and confirmed the diagnosis in the postnatal period. More recently Mahoney et al.2 have reported an abnormal methylmalonic acid concentration in the amniotic fluid of one of two pregnancies at risk. They confirmed that the fetus in this case was affected by showing an impaired oxidation of methylmalonic acid in cultured amniotic cells.

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.

scholarly journals Proteinuria as a presenting sign of combined methylmalonic acidemia and homocysteinemia: case report

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ru-Yue Chen ◽  
Xiao-Zhong Li ◽  
Qiang Lin ◽  
Yun Zhu ◽  
Yun-Yan Shen ◽  
...  
Keyword(s):  
Organic Acids ◽  
Vitamin B12 ◽  
Metabolic Diseases ◽  
Methylmalonic Acid ◽  
Clinical Manifestations ◽  
Methylmalonic Aciduria ◽  
Methylmalonic Acidemia ◽  
Initial Presentation ◽  
Gas Chromatography Mass Spectrometry ◽  
Persistent Proteinuria

Abstract Background Disorders of the metabolism and absorption of vitamin B12 can lead to decrease in activity of methionine synthetase and methylmalonate coenzyme A mutase (MMUT), which results in increased levels of methylmalonic acid and homocysteine in blood and urine. Often, combined methylmalonic acidemia (MMA) and homocysteinemia is misdiagnosed due to a lack of specific symptoms. The clinical manifestations are diverse, but proteinuria as the initial presentation is rare. Case presentation Two cases of MMA with homocysteinemia in children are reported. Proteinuria were a primary presenting symptom, followed by anemia and neurologic symptoms (frequent convulsions and unstable walking, respectively). Screening of amino acids and acyl carnitine in serum showed that the propionyl carnitine:acetylcarnitine ratio increased. Profiling of urinary organic acids by gas chromatography–mass spectrometry revealed high levels of methylmalonic acid. Homocysteine content in blood was increased. Comprehensive genetic analyses of peripheral blood-derived DNA demonstrated heterozygous variants of methylmalonic aciduria type C and homocystinuria (MMACHC) and amnionless (AMN) genes in our two patients, respectively. After active treatment, the clinical manifestations in Case 1 were relieved and urinary protein ceased to be observed; Case 2 had persistent proteinuria and was lost to follow-up. Conclusions Analyses of the organic acids in blood and urine suggested MMA combined with homocysteinemia. In such diseases, reports of renal damage are uncommon and proteinuria as the initial presentation is rare. Molecular analysis indicated two different genetic causes. Although the pathologic mechanisms were related to vitamin B12, the severity and prognosis of renal lesions were different. Therefore, gene detection provides new insights into inherited metabolic diseases.

Two-Dimensional Paper Chromatographic Determination of Amino Acids in Urine

1969 ◽  
Vol 15 (10) ◽  
pp. 1011-1016 ◽  
Author(s):  
Carmine J Spinella
Keyword(s):  
Amino Acids ◽  
Paper Chromatography ◽  
Inborn Errors Of Metabolism ◽  
Chromatographic Determination ◽  
Two Dimensional ◽  
Standard Mixture ◽  
Inborn Errors ◽  
Chromatography Method ◽  
Amino Aciduria

Abstract In an attempt to screen children for amino-aciduria related to various inborn errors of metabolism, a two-dimensional paper chromatography method was developed. This method requires no expensive equipment, resolves a standard mixture of 17 α-amino acids, is consistently reproducible, and requires less than 7 hr from start to visualization of the chromatogram.

scholarly journals Functional neurologic disorders in an adult with propionic acidemia: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Alexis Tarrada ◽  
Solène Frismand-Kryloff ◽  
Coraline Hingray
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Metabolic Diseases ◽  
Neurodevelopmental Disorder ◽  
Propionic Acidemia ◽  
Organic Aciduria ◽  
Obsessive Compulsive ◽  
Inborn Errors ◽  
Neurologic Disorders ◽  
Psychiatric Syndrome ◽  
Obsessive Compulsive Disorders

Abstract Background Inborn errors of metabolism are often characterized by various psychiatric syndromes. Previous studies tend to classify psychiatric manifestations into clinical entities. Among inborn errors of metabolism, propionic acidemia (PA) is a rare inherited organic aciduria that leads to neurologic disabilities. Several studies in children with PA demonstrated that psychiatric disorders are associated to neurological symptoms. To our knowledge, no psychopathological description in adult with propionic acidemia is available. Case presentation We aimed to compare the case of a 53-year-old woman with PA, to the previous psychiatric descriptions in children with PA and in adults with other inborn errors of metabolism. Our patient presented a large variety of signs: functional neurologic disorders, borderline personality traits (emotional dyregulation, dissociative and alexithymic trends, obsessive-compulsive disorders), occurring in a context of neurodevelopmental disorder. Conclusion Clinical and paraclinical examinations are in favor of a mild mental retardation since childhood and disorders of behavior and personality without any definite psychiatric syndrome, as already described in other metabolic diseases (group 3). Nonetheless, further studies are needed to clarify the psychiatric alterations within adult patients with PA.

A Gas Chromatographic Procedure for Detection of Pathological Organic Aciduria

1970 ◽  
Vol 16 (3) ◽  
pp. 212-214 ◽  
Author(s):  
K B Hammond ◽  
S I Goodman
Keyword(s):  
Organic Acids ◽  
Carbon Disulfide ◽  
Dicarboxylic Acids ◽  
Short Chain Fatty Acids ◽  
Methylmalonic Aciduria ◽  
Organic Aciduria ◽  
Glycol Succinate ◽  
Glycol Adipate ◽  
Inborn Errors ◽  
Chromatographic Procedure

Abstract A number of nonamino organic acids associated with inborn errors of metabolism can be detected by gas chromatography. The organic acids are extracted into ethyl acetate and diethyl ether, the extracts combined, and the solvents evaporated under nitrogen. The residue is taken up in carbon disulfide and an aliquot chromatographed on 5% neopentyl glycol adipate to separate short-chain fatty acids (C 2 to 6). The remaining carbon disulfide is evaporated, the residue taken up in methanol, and the acids are methylated with diazomethane. The solvent is evaporated, the residue taken up in tetrahydrofuran, and an aliquot chromatographed on 15% diethylene glycol succinate to separate keto, hydroxy, and dicarboxylic acids. Chromatographic patterns for normal and abnormal urines have been established. Four cases of congenital methylmalonic aciduria have been diagnosed by this procedure.

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.

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