Clinical, enzymatic and molecular characterization of nine new patients with malonyl-coenzyme A decarboxylase deficiency

G. S. Salomons, C. Jakobs, Landegge Pope, A. Errami, M. Potter, M. Nowaczyk, S. Olpin, N. Manning, J. A.J. Raiman, T. Slade, M. P. Champion, D. Peck, D. Gavrilov, R. Hillman, G. E. Hoganson, K. Donaldson, J. P.H. Shield, D. Ketteridge, M. Wasserstein, K. Michael Gibson

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

We report nine new patients with malonic aciduria associated with enzyme-confirmed malonyl-CoA decarboxylase (MCD) deficiency in eight. Clinical details were available on eight, and molecular genetic characterization was obtained for nine. As for 15 previously described patients, cardinal clinical manifestations included developmental delay and cardiomyopathy; metabolic perturbations (e.g. acidosis) and seizures, however, were infrequent or not observed in our patients. For all, detection of elevated malonic acid in urine (± increased C3DC acylcarnitine by analysis employing tandem mass spectrometry) led to pursuit of enzyme studies. MCD activities (nmol/h PER mg protein) revealed: control (n = 22), 16.2 ± 1.8 (SEM; range 5.7-46.2); patients (n = 8, assayed in duplicate), 1.7 ± 0.3 (10% of parallel control; range 0.6-2.8). Molecular characterization by DNA sequence analysis and multiplex ligation-dependent probe amplification revealed nine novel mutations (c.796C>T; p.Gln266X, c.481delC; p.Leu161CysfsX18, c.1367A>C; p.Tyr456Ser, c.1319G>T; p.Ser440Ile, c.1430C>T; p.Ser477Phe, c.899G>T; p.Gly300Val, c.799-1683_949-1293del3128, and two other large genomic deletions comprising exons 1 or the complete gene) and two known mutations in the MLYCD gene. Our findings increase the number of enzyme-confirmed MCD-deficient patients by >50%, and expand our understanding of the phenotypic and molecular heterogeneity of this rare disorder.

Original languageEnglish (US)
Pages (from-to)23-28
Number of pages6
JournalJournal of Inherited Metabolic Disease
Volume30
Issue number1
DOIs
StatePublished - Feb 2007
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Clinical, enzymatic and molecular characterization of nine new patients with malonyl-coenzyme A decarboxylase deficiency'. Together they form a unique fingerprint.

Cite this