Mudd's disease (MAT I/III deficiency): A survey of data for MAT1A homozygotes and compound heterozygotes
Journal
Orphanet Journal of Rare Diseases
Journal Volume
10
Journal Issue
1
Pages
99
Date Issued
2015
Author(s)
Abdenur J.E.
Baronio F.
Bannick A.A.
Corrales F.
Couce M.
Donner M.G.
Ficicioglu C.
Freehauf C.
Frithiof D.
Gotway G.
Hirabayashi K.
Hofstede F.
Hoganson G.
James P.
Kim S.
Korman S.H.
Lachmann R.
Levy H.
Lindner M.
Lykopoulou L.
Mayatepek E.
Muntau A.
Okano Y.
Raymond K.
Rubio-Gozalbo E.
Scholl-B?rgi S.
Schulze A.
Singh R.
Stabler S.
Stuy M.
Thomas J.
Wagner C.
Wilson W.G.
Wortmann S.
Yamamoto S.
Pao M.
Blom H.J.
Abstract
Background: This paper summarizes the results of a group effort to bring together the worldwide available data on patients who are either homozygotes or compound heterozygotes for mutations in MAT1A. MAT1A encodes the subunit that forms two methionine adenosyltransferase isoenzymes, tetrameric MAT I and dimeric MAT III, that catalyze the conversion of methionine and ATP to S-adenosylmethionine (AdoMet). Subnormal MAT I/III activity leads to hypermethioninemia. Individuals, with hypermethioninemia due to one of the MAT1A mutations that in heterozygotes cause relatively mild and clinically benign hypermethioninemia are currently often being flagged in screening programs measuring methionine elevation to identify newborns with defective cystathionine β-synthase activity. Homozygotes or compound heterozygotes for MAT1A mutations are less frequent. Some but not all, such individuals have manifested demyelination or other CNS abnormalities. Purpose of the study: The goals of the present effort have been to determine the frequency of such abnormalities, to find how best to predict whether they will occur, and to evaluate the outcomes of the variety of treatment regimens that have been used. Data have been gathered for 64 patients, of whom 32 have some evidence of CNS abnormalities (based mainly on MRI findings), and 32 do not have such evidence. Results and Discussion: The results show that mean plasma methionine concentrations provide the best indication of the group into which a given patient will fall: those with means of 800 μM or higher usually have evidence of CNS abnormalities, whereas those with lower means usually do not. Data are reported for individual patients for MAT1A genotypes, plasma methionine, total homocysteine (tHcy), and AdoMet concentrations, liver function studies, results of 15 pregnancies, and the outcomes of dietary methionine restriction and/or AdoMet supplementation. Possible pathophysiological mechanisms that might contribute to CNS damage are discussed, and tentative suggestions are put forth as to optimal management. ? 2015 Chien et al.
SDGs
Other Subjects
cystathionine; homocysteine; methionine; methionine adenosyltransferase; pyridoxine; s adenosylmethionine; MAT1A protein, human; methionine adenosyltransferase; adult; amino acid blood level; Article; central nervous system disease; child; controlled study; diet restriction; drug megadose; female; gene; gene mutation; genetic disorder; genotype; heterozygote; homozygote; human; liver cell carcinoma; liver function; major clinical study; male; MAT1A gene; Mudd disease; outcome assessment; pregnancy outcome; adolescent; disorders of amino acid and protein metabolism; genetics; heterozygote; homozygote; infant; middle aged; preschool child; questionnaire; young adult; Adolescent; Adult; Amino Acid Metabolism, Inborn Errors; Child, Preschool; Female; Heterozygote; Homozygote; Humans; Infant; Male; Methionine Adenosyltransferase; Middle Aged; Surveys and Questionnaires; Young Adult
Publisher
BioMed Central Ltd.
Type
journal article