Delineating the clinical spectrum of isolated methylmalonic acidurias: cblA and mut.


INTRODUCTION:Long-term outcome is postulated to be different in isolated methylmalonic aciduria caused by mutations in the MMAA gene (cblA type) compared with methylmalonyl-CoA mutase deficiency (mut), but case definition was previously difficult. METHOD:Cross-sectional analysis of data from the European Registry and Network for Intoxication type Metabolic Diseases (Chafea no. December 1, 2010). RESULTS:Data from 28 cblA and 95 mut patients in most cases confirmed by mutation analysis (including 4 new mutations for cblA and 19 new mutations for mut). Metabolic crisis is the predominant symptom leading to diagnosis in both groups. Biochemical disturbances during the first crisis were similar in both groups, as well as the age at diagnosis. Z scores of body height and body weight were similar in both groups at birth, but were significantly lower in the mut group at the time of last visit. Glomerular filtration rate was significantly higher in cblA; and as a consequence, chronic renal failure and related complications were significantly less frequent and renal function could be preserved even in older patients. Neurological complications were predominantly found in the mut subgroup. Methylmalonic acidemia (MMA) levels in urine and plasma were significantly lower in cblA. 27/28 cblA patients were reported to be responsive to cobalamin, only 86% of cblA patients were treated with i.m. hydroxocobalamin. In total, 73% of cblA and 98% of mut patients followed a calculated diet with amino acid supplements in 27% (cblA) and 69% (mut). During the study interval, six patients from the mut group died, while all cblA patients survived. CONCLUSION:Although similar at first, cblA patients respond to hydroxocobalamin treatment, subsequently show significantly lower levels of MMA and a milder course than mut patients.


J Inherit Metab Dis


Hörster F,Tuncel AT,Gleich F,Plessl T,Froese SD,Garbade SF,Kölker S,Baumgartner MR,Additional Contributors from E-IMD.




Has Abstract


2021-01-01 00:00:00












  • Prediction of outcome in isolated methylmalonic acidurias: combined use of clinical and biochemical parameters.

    abstract::Objectives Isolated methylmalonic acidurias (MMAurias) are caused by deficiency of methylmalonyl-CoA mutase or by defects in the synthesis of its cofactor 5'-deoxyadenosylcobalamin. The aim of this study was to evaluate which parameters best predicted the long-term outcome. Methods Standardized questionnaires were sen...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,多中心研究


    authors: Hörster F,Garbade SF,Zwickler T,Aydin HI,Bodamer OA,Burlina AB,Das AM,De Klerk JBC,Dionisi-Vici C,Geb S,Gökcay G,Guffon N,Maier EM,Morava E,Walter JH,Schwahn B,Wijburg FA,Lindner M,Grünewald S,Baumgartner MR,Kölke

    更新日期:2009-10-01 00:00:00

  • Alpha- and beta-mannosidoses.

    abstract::Clinical, pathological and biochemical findings in the mannosidoses are described. Family studies showed granulocyte-rich white cell fractions to be the tissue of choice for carrier detection in beta-mannosidosis. Metabolic labelling studies using [3H] mannose demonstrated accumulation of Man beta 1-4GlcNAc in culture...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


    authors: Cooper A,Hatton CE,Thornley M,Sardharwalla IB

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  • The impact of the immune system on the safety and efficiency of enzyme replacement therapy in lysosomal storage disorders.

    abstract::In the light of clinical experience in infantile onset Pompe patients, the immunological impact on the tolerability and long-term efficacy of enzyme replacement therapy (ERT) for lysosomal storage disorders has come under renewed scrutiny. This article details the currently proposed immunological mechanisms involved i...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,评审


    authors: Broomfield A,Jones SA,Hughes SM,Bigger BW

    更新日期:2016-07-01 00:00:00

  • Analysis of synaptic proteins in the cerebrospinal fluid as a new tool in the study of inborn errors of neurotransmission.

    abstract::In a few rare diseases, specialised studies in cerebrospinal fluid (CSF) are required to identify the underlying metabolic disorder. We aimed to explore the possibility of detecting key synaptic proteins in the CSF, in particular dopaminergic and gabaergic, as new procedures that could be useful for both pathophysiolo...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


    authors: Duarte ST,Ortez C,Pérez A,Artuch R,García-Cazorla A

    更新日期:2011-04-01 00:00:00

  • Mitochondrial myopathies.

    abstract::The mitochondrial myopathies or encephalomyopathies with known biochemical defects can be divided into 5 groups: (1) defects of mitochondrial transport, such as CPT deficiency or carnitine deficiencies; (2) defects of substrate utilization, such as PDHC deficiency or defects of beta-oxidation; (3) defects of the Krebs...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,评审


    authors: DiMauro S,Bonilla E,Zeviani M,Servidei S,DeVivo DC,Schon EA

    更新日期:1987-01-01 00:00:00

  • Clinical overview and treatment options for non-skeletal manifestations of mucopolysaccharidosis type IVA.

    abstract::Mucopolysaccharidosis type IVA (MPS IVA) or Morquio syndrome is a multisystem disorder caused by galactosamine-6-sulfatase deficiency. Skeletal manifestations, including short stature, skeletal dysplasia, cervical instability, and joint destruction, are known to be associated with this condition. Due to the severity o...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,评审


    authors: Hendriksz CJ,Al-Jawad M,Berger KI,Hawley SM,Lawrence R,Mc Ardle C,Summers CG,Wright E,Braunlin E

    更新日期:2013-03-01 00:00:00

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    abstract::L-2-hydroxyglutaric aciduria (L-2-HGA) is a metabolic disease with an autosomal recessive mode of inheritance. It was first reported in 1980. Patients with this disease have mutations in both alleles of the L2HDGH gene. The clinical presentation of individuals with L-2-HGA is somewhat variable, but affected individual...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,多中心研究


    authors: Sass JO,Jobard F,Topçu M,Mahfoud A,Werlé E,Cure S,Al-Sannaa N,Alshahwan SA,Bataillard M,Cimbalistiene L,Grolik C,Kemmerich V,Omran H,Sztriha L,Tabache M,Fischer J

    更新日期:2008-12-01 00:00:00

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    journal_title:Journal of inherited metabolic disease

    pub_type: 临床试验,杂志文章


    authors: Grigorescu Sido P,Drugan C,Cret V,Al-Kzouz C,Denes C,Coldea C,Zimmermann A

    更新日期:2007-10-01 00:00:00

  • Pyrimidine and purine metabolites in ornithine carbamoyl transferase deficiency.

    abstract::Detailed biochemical studies have been carried out in a female heterozygote for ornithine carbamoyl-transferase (OCT) deficiency. Increased levels of the pyrimidines, orotic acid, uridine and uracil, were observed in plasma as well as urine by utilizing an adaptation of high performance liquid chromatography (HPLC). U...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


    authors: Webster DR,Simmonds HA,Barry DM,Becroft DM

    更新日期:1981-01-01 00:00:00

  • Carnitine deficiency with cardiomyopathy presenting as neonatal hydrops: successful response to carnitine therapy.

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    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


    authors: Steenhout P,Elmer C,Clercx A,Blum D,Gnat D,van Erum S,Vertongen F,Vamos E

    更新日期:1990-01-01 00:00:00

  • Pathogenic cascades in lysosomal disease-Why so complex?

    abstract::Lysosomal disease represents a large group of more than 50 clinically recognized conditions resulting from inborn errors of metabolism affecting the organelle known as the lysosome. The lysosome is an integral part of the larger endosomal/lysosomal system, and is closely allied with the ubiquitin-proteosomal and autop...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,评审


    authors: Walkley SU

    更新日期:2009-04-01 00:00:00

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    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


    authors: Balwani M,Grace ME,Desnick RJ

    更新日期:2011-06-01 00:00:00

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    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,评审


    authors: Aicardi J

    更新日期:1993-01-01 00:00:00

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    pub_type: 杂志文章


    authors: Estrella J,Wilcken B,Carpenter K,Bhattacharya K,Tchan M,Wiley V

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    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


    authors: Hargreaves IP,Heales SJ,Briddon A,Lee PJ,Hanna MG,Land JM

    更新日期:2003-01-01 00:00:00

  • Co-cultivation of Niemann-Pick disease type C fibroblasts belonging to complementation groups alpha and beta stimulates LDL-derived cholesterol esterification.

    abstract::Niemann-Pick disease type C (NPC) is a neurovisceral storage disorder with an unknown primary deficiency. Somatic cell hybridization experiments using human cultured fibroblasts have shown that two complementation groups (NPC-alpha and NPC-beta) are associated with the biochemical and clinical phenotypes comprising NP...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


    authors: Steinberg SJ,Mondal D,Fensom AH

    更新日期:1996-01-01 00:00:00

  • Adenosine, dopamine and serotonin receptors imbalance in lymphocytes of Lesch-Nyhan patients.

    abstract::Lesch-Nyhan disease (LND) is caused by complete deficiency of the hypoxanthine-guanine phosphoribosyltransferase enzyme. It is characterized by overproduction of uric acid, jointly with severe motor disability and self-injurious behaviour which physiopathology is unknown. These neurological manifestations suggest a dy...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


    authors: García MG,Puig JG,Torres RJ

    更新日期:2012-11-01 00:00:00

  • Neuropsychological outcomes of several storage diseases with and without bone marrow transplantation.

    abstract::Neuropsychological assessment is essential in providing documentation of the untreated natural history of storage diseases associated with dementia and quantifying the effectiveness of treatment on central nervous system function. Baseline characterization and outcome of bone marrow transplantation (BMT) for three leu...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,评审


    authors: Shapiro EG,Lockman LA,Balthazor M,Krivit W

    更新日期:1995-01-01 00:00:00

  • Methionine adenosyltransferase (MAT) I/III deficiency with concurrent hyperhomocysteinaemia: two novel cases.

    abstract::This study reports three novel mutations of the methionine adenosyltransferase (MAT) lA gene and confirms that hyperhomocysteinaemia may be a characteristic finding in MAT I/III deficiency. Thus, MAT I/III deficiency is important in the differential diagnoses of hyperhomocysteinaemia, which may lead to clinical compli...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


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    更新日期:2005-01-01 00:00:00

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    abstract:BACKGROUND:Farber disease (FD) is a rare, lysosomal storage disorder caused by deficient acid ceramidase activity. FD has long been considered a fatal disorder with death in the first three decades of life resulting either from respiratory insufficiency as a consequence of airway involvement or from progressive neurode...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


    authors: Ehlert K,Levade T,Di Rocco M,Lanino E,Albert MH,Führer M,Jarisch A,Güngör T,Ayuk F,Vormoor J

    更新日期:2019-03-01 00:00:00

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    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


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    更新日期:2011-06-01 00:00:00

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    abstract::The retinal and neurological complications of abetalipoproteinaemia may be preventable by replacing vitamins A and E from an early age, but their role in adult presentations is less clear. Two adult females with abetalipoproteinaemia have received 8 and 10 years respectively of replacement therapy with vitamins A, E a...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


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    更新日期:1988-01-01 00:00:00

  • Correlation between the molecular effects of mutations at the dimer interface of alanine-glyoxylate aminotransferase leading to primary hyperoxaluria type I and the cellular response to vitamin B6.

    abstract::Primary hyperoxaluria type I (PH1) is a rare disease caused by the deficit of liver alanine-glyoxylate aminotransferase (AGT). AGT prevents oxalate formation by converting peroxisomal glyoxylate to glycine. When the enzyme is deficient, progressive calcium oxalate stones deposit first in the urinary tract and then at ...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


    authors: Dindo M,Oppici E,Dell'Orco D,Montone R,Cellini B

    更新日期:2018-03-01 00:00:00

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    abstract::Hexosaminidase A activities were determined in tears and peripheral leukocytes of carriers and noncarriers for Tay-Sachs Disease (TSD) as a percentage of total hexosaminidase activity. Correlation between enzyme activities in tears and leukocytes was highly significant (r = 0.75, p less than 0.01). Compared to leukocy...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


    authors: Buchalter MS,Wannmacher CM,Wajner M

    更新日期:1984-01-01 00:00:00

  • Regression of neuropsychological deficits in early-treated phenylketonurics during adolescence.

    abstract::Even early-treated phenylketonuric patients suffer from phenylalanine-associated (mild) neuropsychological impairment. To date it is still unclear whether patients' deficits show a progression on ageing. This unsolved question seems to be an important aspect in the still ongoing debate about how long and how strictly ...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


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    更新日期:1999-08-01 00:00:00

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    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,评审


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    更新日期:1992-01-01 00:00:00

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    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


    authors: Smith I,Hyland K,Kendall B

    更新日期:1985-01-01 00:00:00

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    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


    authors: Ghiasvand NM,Aledavood A,Ghiasvand R,Seyedin Borojeny F,Aledavood AR,Seyed S,Miner W,Saeb Taheri GR

    更新日期:2009-12-01 00:00:00

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    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章


    authors: Brandt NJ

    更新日期:1984-01-01 00:00:00

  • Angiogenesis in alkaptonuria.

    abstract::Alkaptonuria (AKU) is a rare genetic disease that affects the entire joint. Current standard of AKU treatment is palliative and little is known about its physiopathology. Neovascularization is involved in the pathogenesis of systemic inflammatory rheumatic diseases, a family of related disorders that includes AKU. Her...

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    pub_type: 杂志文章


    authors: Millucci L,Bernardini G,Marzocchi B,Braconi D,Geminiani M,Gambassi S,Laschi M,Frediani B,Galvagni F,Orlandini M,Santucci A

    更新日期:2016-11-01 00:00:00