Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Störungen des Cobalaminstoffwechsels

Die Cobalamin-Stoffwechselstörungen überlappen mit der Methylmalonazidurie, da der Methylmalonazidurie eine Störung des Cobalamin-Stoffwechsels zugrunde liegt. Es sind autosomal rezessive Stoffwechselerkrankungen bei denen sich neben der erhöhten Konzentration von Methylmalonsäure in Blut und Urin auch megaloblastäre Anämien finden lassen.

Symptome

Anämie
Bei Cobalaminstoffwechselstörungen ist die Anämie makrozytär.

Gliederung

Erbliche Stoffwechselerkrankungen
Acoeruloplasminämie/Hypocoeruloplasminämie
Coenzym Q10-Mangel
Erbliche Fettstoffwechselerkrankungen
Genetisch bedingte Hyperbilirubinämie
Glycolipidose
HADH-Mangel
Hypomagnesiämie
Hypomethylierungs-Syndrom
Kongenitale Glykosilierungsstörung
Lebensmittelunverträglichkeiten
Lysosomale Speicherkrankheiten
MELAS-Syndrom
Methioninadenosyltransferase-Mangel
Störungen des Cobalaminstoffwechsels
Homozysteinurie und megaloblastäre Anämie cblE
MTRR
Homozysteinurie und megaloblastäre Anämie cblG
MTR
Methylmalonazidurie Typ mut
MUT
Methylmalonazidurie cblA
MMAA
Methylmalonazidurie cblB
MMAB
Methylmalonazidurie mit Homozysteinurie cblC
MMACHC
Methylmalonazidurie mit Homozysteinurie cblD
MMADHC
Methylmalonazidurie mit Homozysteinurie cblF
LMBRD1
Methylmalonazidurie mit Homozysteinurie cblJ
ABCD4
Störungen des Eisenstoffwechsels
Störungen des Glucosestoffwechsels
Störungen des Harnstoffzyklus
Störungen des Harnsäurestoffwechsels
Störungen des Phosphathaushaltes

Referenzen:

1.

Acquaviva C et. al. (2001) N219Y, a new frequent mutation among mut(degree) forms of methylmalonic acidemia in Caucasian patients.

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2.

Bodamer OA et. al. (2001) Adult-onset combined methylmalonic aciduria and homocystinuria (cblC).

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3.

Lerner-Ellis JP et. al. (2006) Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type.

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4.

Morel CF et. al. (2006) Combined methylmalonic aciduria and homocystinuria (cblC): phenotype-genotype correlations and ethnic-specific observations.

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5.

Ben-Omran TI et. al. (2007) Late-onset cobalamin-C disorder: a challenging diagnosis.

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6.

Tsai AC et. al. (2007) Late-onset combined homocystinuria and methylmalonic aciduria (cblC) and neuropsychiatric disturbance.

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7.

Lerner-Ellis JP et. al. (2009) Spectrum of mutations in MMACHC, allelic expression, and evidence for genotype-phenotype correlations.

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8.

Liu MY et. al. (2010) Mutation spectrum of MMACHC in Chinese patients with combined methylmalonic aciduria and homocystinuria.

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9.

Kömhoff M et. al. (2013) Combined pulmonary hypertension and renal thrombotic microangiopathy in cobalamin C deficiency.

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10.

Sharma AP et. al. (2007) Hemolytic uremic syndrome (HUS) secondary to cobalamin C (cblC) disorder.

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11.

Cooper BA et. al. (1990) Methylmalonic aciduria due to a new defect in adenosylcobalamin accumulation by cells.

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12.

Goodman SI et. al. (1970) Homocystinuria with methylmalonic aciduria: two cases in a sibship.

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13.

Suormala T et. al. (2004) The cblD defect causes either isolated or combined deficiency of methylcobalamin and adenosylcobalamin synthesis.

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14.

Coelho D et. al. (2008) Gene identification for the cblD defect of vitamin B12 metabolism.

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15.

Stucki M et. al. (2012) Molecular mechanisms leading to three different phenotypes in the cblD defect of intracellular cobalamin metabolism.

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16.

Testai FD et al. (2010) Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders.

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17.

Willard HF et. al. (1978) Genetic complementation among inherited deficiencies of methylmalonyl-CoA mutase activity: evidence for a new class of human cobalamin mutant.

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18.

Mellman I et. al. (1978) Cobalamin binding and cobalamin-dependent enzyme activity in normal and mutant human fibroblasts.

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19.

Fenton WA et. al. (1978) Genetic and biochemical analysis of human cobalamin mutants in cell culture.

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20.

Carmel R et. al. (1980) Congenital methylmalonic aciduria--homocystinuria with megaloblastic anemia: observations on response to hydroxocobalamin and on the effect of homocysteine and methionine on the deoxyuridine suppression test.

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21.

Watkins D et. al. (2000) Complementation studies in the cblA class of inborn error of cobalamin metabolism: evidence for interallelic complementation and for a new complementation class (cblH).

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22.

Mudd SH et. al. (1970) Deranged B 12 metabolism: studies of fibroblasts grown in tissue culture.

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23.

Mudd SH et. al. (1969) A derangement in B 12 metabolism leading to homocystinemia, cystathioninemia and methylmalonic aciduria.

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24.

None (1969) Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis.

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25.

Shinnar S et. al. (1984) Cobalamin C mutation (methylmalonic aciduria and homocystinuria) in adolescence. A treatable cause of dementia and myelopathy.

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26.

Rosenblatt DS et. al. (1997) Clinical heterogeneity and prognosis in combined methylmalonic aciduria and homocystinuria (cblC).

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27.

Cerone R et. al. (1999) Minor facial anomalies in combined methylmalonic aciduria and homocystinuria due to a defect in cobalamin metabolism.

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28.

Enns GM et. al. (1999) Progressive neurological deterioration and MRI changes in cblC methylmalonic acidaemia treated with hydroxocobalamin.

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29.

Andersson HC et. al. () Long-term outcome in treated combined methylmalonic acidemia and homocystinemia.

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30.

Van Hove JL et. al. (2002) Cobalamin disorder Cbl-C presenting with late-onset thrombotic microangiopathy.

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31.

Schimel AM et. al. (2006) The natural history of retinal degeneration in association with cobalamin C (cbl C) disease.

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32.

Kaplan P et. al. (2006) Liver transplantation is not curative for methylmalonic acidopathy caused by methylmalonyl-CoA mutase deficiency.

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33.

Kruszka PS et. al. (2013) Renal growth in isolated methylmalonic acidemia.

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