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Abnormal circulating vitamin B12 concentration

MedGen UID:
866685
Concept ID:
C4021032
Finding
Synonyms: Abnormal serum cobalamin level; Abnormal vitamin B12 level
 
HPO: HP:0040126

Definition

A deviation from the normal concentration of cobalamin (vitamin B12) in the blood. Vitamin B12 is one of the eight B vitamins. [from HPO]

Conditions with this feature

Transcobalamin II deficiency
MedGen UID:
137976
Concept ID:
C0342701
Disease or Syndrome
Transcobalamin II deficiency is an autosomal recessive disorder with onset in early infancy characterized by failure to thrive, megaloblastic anemia, and pancytopenia. Other features include methylmalonic aciduria, recurrent infections, and vomiting and diarrhea. Treatment with cobalamin results in clinical improvement, but the untreated disorder may result in mental retardation and neurologic abnormalities (summary by Haberle et al., 2009). Hall (1981) gave a clinically oriented review of congenital defects of vitamin B12 transport, and Frater-Schroder (1983) gave a genetically oriented review.
Cobalamin C disease
MedGen UID:
341256
Concept ID:
C1848561
Disease or Syndrome
Disorders of intracellular cobalamin metabolism have a variable phenotype and age of onset that are influenced by the severity and location within the pathway of the defect. The prototype and best understood phenotype is cblC; it is also the most common of these disorders. The age of initial presentation of cblC spans a wide range: In utero with fetal presentation of nonimmune hydrops, cardiomyopathy, and intrauterine growth restriction. Newborns, who can have microcephaly, poor feeding, and encephalopathy. Infants, who can have poor feeding and slow growth, neurologic abnormality, and, rarely, hemolytic uremic syndrome (HUS). Toddlers, who can have poor growth, progressive microcephaly, cytopenias (including megaloblastic anemia), global developmental delay, encephalopathy, and neurologic signs such as hypotonia and seizures. Adolescents and adults, who can have neuropsychiatric symptoms, progressive cognitive decline, thromboembolic complications, and/or subacute combined degeneration of the spinal cord.
Methylmalonic aciduria, cblB type
MedGen UID:
344420
Concept ID:
C1855102
Disease or Syndrome
For this GeneReview, the term "isolated methylmalonic acidemia" refers to a group of inborn errors of metabolism associated with elevated methylmalonic acid (MMA) concentration in the blood and urine that result from the failure to isomerize (convert) methylmalonyl-coenzyme A (CoA) into succinyl-CoA during propionyl-CoA metabolism in the mitochondrial matrix, without hyperhomocysteinemia or homocystinuria, hypomethioninemia, or variations in other metabolites, such as malonic acid. Isolated MMA is caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut0 enzymatic subtype or mut– enzymatic subtype, respectively), a defect in the transport or synthesis of its cofactor, 5-deoxy-adenosyl-cobalamin (cblA, cblB, or cblD-MMA), or deficiency of the enzyme methylmalonyl-CoA epimerase. Prior to the advent of newborn screening, common phenotypes included: Infantile/non-B12-responsive form (mut0 enzymatic subtype, cblB), the most common phenotype, associated with infantile-onset lethargy, tachypnea, hypothermia, vomiting, and dehydration on initiation of protein-containing feeds. Without appropriate treatment, the infantile/non-B12-responsive phenotype could rapidly progress to coma due to hyperammonemic encephalopathy. Partially deficient or B12-responsive phenotypes (mut– enzymatic subtype, cblA, cblB [rare], cblD-MMA), in which symptoms occur in the first few months or years of life and are characterized by feeding problems, failure to thrive, hypotonia, and developmental delay marked by episodes of metabolic decompensation. Methylmalonyl-CoA epimerase deficiency, in which findings range from complete absence of symptoms to severe metabolic acidosis. Affected individuals can also develop ataxia, dysarthria, hypotonia, mild spastic paraparesis, and seizures. In those individuals diagnosed by newborn screening and treated from an early age, there appears to be decreased early mortality, less severe symptoms at diagnosis, favorable short-term neurodevelopmental outcome, and lower incidence of movement disorders and irreversible cerebral damage. However, secondary complications may still occur and can include intellectual disability, tubulointerstitial nephritis with progressive impairment of renal function, "metabolic stroke" (bilateral lacunar infarction of the basal ganglia during acute metabolic decompensation), pancreatitis, growth failure, functional immune impairment, bone marrow failure, optic nerve atrophy, arrhythmias and/or cardiomyopathy (dilated or hypertrophic), liver steatosis/fibrosis/cancer, and renal cancer.
Methylmalonic aciduria, cblA type
MedGen UID:
344422
Concept ID:
C1855109
Disease or Syndrome
For this GeneReview, the term "isolated methylmalonic acidemia" refers to a group of inborn errors of metabolism associated with elevated methylmalonic acid (MMA) concentration in the blood and urine that result from the failure to isomerize (convert) methylmalonyl-coenzyme A (CoA) into succinyl-CoA during propionyl-CoA metabolism in the mitochondrial matrix, without hyperhomocysteinemia or homocystinuria, hypomethioninemia, or variations in other metabolites, such as malonic acid. Isolated MMA is caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut0 enzymatic subtype or mut– enzymatic subtype, respectively), a defect in the transport or synthesis of its cofactor, 5-deoxy-adenosyl-cobalamin (cblA, cblB, or cblD-MMA), or deficiency of the enzyme methylmalonyl-CoA epimerase. Prior to the advent of newborn screening, common phenotypes included: Infantile/non-B12-responsive form (mut0 enzymatic subtype, cblB), the most common phenotype, associated with infantile-onset lethargy, tachypnea, hypothermia, vomiting, and dehydration on initiation of protein-containing feeds. Without appropriate treatment, the infantile/non-B12-responsive phenotype could rapidly progress to coma due to hyperammonemic encephalopathy. Partially deficient or B12-responsive phenotypes (mut– enzymatic subtype, cblA, cblB [rare], cblD-MMA), in which symptoms occur in the first few months or years of life and are characterized by feeding problems, failure to thrive, hypotonia, and developmental delay marked by episodes of metabolic decompensation. Methylmalonyl-CoA epimerase deficiency, in which findings range from complete absence of symptoms to severe metabolic acidosis. Affected individuals can also develop ataxia, dysarthria, hypotonia, mild spastic paraparesis, and seizures. In those individuals diagnosed by newborn screening and treated from an early age, there appears to be decreased early mortality, less severe symptoms at diagnosis, favorable short-term neurodevelopmental outcome, and lower incidence of movement disorders and irreversible cerebral damage. However, secondary complications may still occur and can include intellectual disability, tubulointerstitial nephritis with progressive impairment of renal function, "metabolic stroke" (bilateral lacunar infarction of the basal ganglia during acute metabolic decompensation), pancreatitis, growth failure, functional immune impairment, bone marrow failure, optic nerve atrophy, arrhythmias and/or cardiomyopathy (dilated or hypertrophic), liver steatosis/fibrosis/cancer, and renal cancer.
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
MedGen UID:
344424
Concept ID:
C1855114
Disease or Syndrome
For this GeneReview, the term "isolated methylmalonic acidemia" refers to a group of inborn errors of metabolism associated with elevated methylmalonic acid (MMA) concentration in the blood and urine that result from the failure to isomerize (convert) methylmalonyl-coenzyme A (CoA) into succinyl-CoA during propionyl-CoA metabolism in the mitochondrial matrix, without hyperhomocysteinemia or homocystinuria, hypomethioninemia, or variations in other metabolites, such as malonic acid. Isolated MMA is caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut0 enzymatic subtype or mut– enzymatic subtype, respectively), a defect in the transport or synthesis of its cofactor, 5-deoxy-adenosyl-cobalamin (cblA, cblB, or cblD-MMA), or deficiency of the enzyme methylmalonyl-CoA epimerase. Prior to the advent of newborn screening, common phenotypes included: Infantile/non-B12-responsive form (mut0 enzymatic subtype, cblB), the most common phenotype, associated with infantile-onset lethargy, tachypnea, hypothermia, vomiting, and dehydration on initiation of protein-containing feeds. Without appropriate treatment, the infantile/non-B12-responsive phenotype could rapidly progress to coma due to hyperammonemic encephalopathy. Partially deficient or B12-responsive phenotypes (mut– enzymatic subtype, cblA, cblB [rare], cblD-MMA), in which symptoms occur in the first few months or years of life and are characterized by feeding problems, failure to thrive, hypotonia, and developmental delay marked by episodes of metabolic decompensation. Methylmalonyl-CoA epimerase deficiency, in which findings range from complete absence of symptoms to severe metabolic acidosis. Affected individuals can also develop ataxia, dysarthria, hypotonia, mild spastic paraparesis, and seizures. In those individuals diagnosed by newborn screening and treated from an early age, there appears to be decreased early mortality, less severe symptoms at diagnosis, favorable short-term neurodevelopmental outcome, and lower incidence of movement disorders and irreversible cerebral damage. However, secondary complications may still occur and can include intellectual disability, tubulointerstitial nephritis with progressive impairment of renal function, "metabolic stroke" (bilateral lacunar infarction of the basal ganglia during acute metabolic decompensation), pancreatitis, growth failure, functional immune impairment, bone marrow failure, optic nerve atrophy, arrhythmias and/or cardiomyopathy (dilated or hypertrophic), liver steatosis/fibrosis/cancer, and renal cancer.
Methylcobalamin deficiency type cblG
MedGen UID:
344426
Concept ID:
C1855128
Disease or Syndrome
Disorders of intracellular cobalamin metabolism have a variable phenotype and age of onset that are influenced by the severity and location within the pathway of the defect. The prototype and best understood phenotype is cblC; it is also the most common of these disorders. The age of initial presentation of cblC spans a wide range: In utero with fetal presentation of nonimmune hydrops, cardiomyopathy, and intrauterine growth restriction. Newborns, who can have microcephaly, poor feeding, and encephalopathy. Infants, who can have poor feeding and slow growth, neurologic abnormality, and, rarely, hemolytic uremic syndrome (HUS). Toddlers, who can have poor growth, progressive microcephaly, cytopenias (including megaloblastic anemia), global developmental delay, encephalopathy, and neurologic signs such as hypotonia and seizures. Adolescents and adults, who can have neuropsychiatric symptoms, progressive cognitive decline, thromboembolic complications, and/or subacute combined degeneration of the spinal cord.

Recent clinical studies

Etiology

McDonnell M, Sartain S, Westoby C, Katarachia V, Wootton SA, Cummings JRF
Nutrients 2023 Nov 14;15(22) doi: 10.3390/nu15224777. PMID: 38004171Free PMC Article
Li M, Chen X, Zhang Y, Chen H, Wang D, Cao C, Jiang Y, Huang X, Dou Y, Wang Y, Ma X, Sheng W, Yan W, Huang G; Birth Defect Prevention Group
J Nutr 2022 Jun 9;152(6):1496-1506. doi: 10.1093/jn/nxac050. PMID: 35259272
Taneja K, Taneja J, Kaur C, Patel S, Haldar D
Clin Lab 2020 Oct 1;66(10) doi: 10.7754/Clin.Lab.2020.200120. PMID: 33073941
Deshmukh U, Katre P, Yajnik CS
Nestle Nutr Inst Workshop Ser 2013;74:145-54; discussion 154-6. Epub 2013 Jul 19 doi: 10.1159/000348463. PMID: 23887113
Obeid R, Holzgreve W, Pietrzik K
J Perinat Med 2013 Sep 1;41(5):469-83. doi: 10.1515/jpm-2012-0256. PMID: 23482308

Diagnosis

Taneja K, Taneja J, Kaur C, Patel S, Haldar D
Clin Lab 2020 Oct 1;66(10) doi: 10.7754/Clin.Lab.2020.200120. PMID: 33073941
Nilsson K, Gustafson L, Hultberg B
Dement Geriatr Cogn Disord 1999 Nov-Dec;10(6):476-82. doi: 10.1159/000017193. PMID: 10559563

Therapy

Obeid R, Holzgreve W, Pietrzik K
J Perinat Med 2013 Sep 1;41(5):469-83. doi: 10.1515/jpm-2012-0256. PMID: 23482308
Cavalieri M, Schmidt R, Chen C, Mok V, de Freitas GR, Song S, Yi Q, Ropele S, Grazer A, Homayoon N, Enzinger C, Loh K, Wong KS, Wong A, Xiong Y, Chang HM, Wong MC, Fazekas F, Eikelboom JW, Hankey GJ; VITATOPS Trial Study Group
Stroke 2012 Dec;43(12):3266-70. Epub 2012 Oct 23 doi: 10.1161/STROKEAHA.112.665703. PMID: 23093615
Nilsson K, Gustafson L, Hultberg B
Dement Geriatr Cogn Disord 1999 Nov-Dec;10(6):476-82. doi: 10.1159/000017193. PMID: 10559563
Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP, Riezler R, Vermaak WJ
J Clin Invest 1996 Jul 1;98(1):177-84. doi: 10.1172/JCI118763. PMID: 8690790Free PMC Article
Skurnick JH, Bogden JD, Baker H, Kemp FW, Sheffet A, Quattrone G, Louria DB
J Acquir Immune Defic Syndr Hum Retrovirol 1996 May 1;12(1):75-83. doi: 10.1097/00042560-199605010-00011. PMID: 8624765

Prognosis

Taneja K, Taneja J, Kaur C, Patel S, Haldar D
Clin Lab 2020 Oct 1;66(10) doi: 10.7754/Clin.Lab.2020.200120. PMID: 33073941
Deshmukh U, Katre P, Yajnik CS
Nestle Nutr Inst Workshop Ser 2013;74:145-54; discussion 154-6. Epub 2013 Jul 19 doi: 10.1159/000348463. PMID: 23887113
Fimognari FL, Loffredo L, Di Simone S, Sampietro F, Pastorelli R, Monaldo M, Violi F, D'Angelo A
Nutr Metab Cardiovasc Dis 2009 Nov;19(9):654-9. Epub 2009 Mar 17 doi: 10.1016/j.numecd.2008.12.006. PMID: 19282159
Hoffer LJ
Curr Opin Clin Nutr Metab Care 2002 Sep;5(5):511-7. doi: 10.1097/00075197-200209000-00009. PMID: 12172474
Carmel R
Am J Clin Pathol 1983 May;79(5):611-5. doi: 10.1093/ajcp/79.5.611. PMID: 6837526

Clinical prediction guides

Taneja K, Taneja J, Kaur C, Patel S, Haldar D
Clin Lab 2020 Oct 1;66(10) doi: 10.7754/Clin.Lab.2020.200120. PMID: 33073941
Oussalah A, Levy J, Filhine-Trésarrieu P, Namour F, Guéant JL
Am J Clin Nutr 2017 Oct;106(4):1142-1156. Epub 2017 Aug 16 doi: 10.3945/ajcn.117.156349. PMID: 28814397Free PMC Article
Deshmukh U, Katre P, Yajnik CS
Nestle Nutr Inst Workshop Ser 2013;74:145-54; discussion 154-6. Epub 2013 Jul 19 doi: 10.1159/000348463. PMID: 23887113
Fimognari FL, Loffredo L, Di Simone S, Sampietro F, Pastorelli R, Monaldo M, Violi F, D'Angelo A
Nutr Metab Cardiovasc Dis 2009 Nov;19(9):654-9. Epub 2009 Mar 17 doi: 10.1016/j.numecd.2008.12.006. PMID: 19282159
Hoffer LJ
Curr Opin Clin Nutr Metab Care 2002 Sep;5(5):511-7. doi: 10.1097/00075197-200209000-00009. PMID: 12172474

Recent systematic reviews

McDonnell M, Sartain S, Westoby C, Katarachia V, Wootton SA, Cummings JRF
Nutrients 2023 Nov 14;15(22) doi: 10.3390/nu15224777. PMID: 38004171Free PMC Article
Oussalah A, Levy J, Filhine-Trésarrieu P, Namour F, Guéant JL
Am J Clin Nutr 2017 Oct;106(4):1142-1156. Epub 2017 Aug 16 doi: 10.3945/ajcn.117.156349. PMID: 28814397Free PMC Article

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