A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening.
Isovaleric acidemia (IVA) is an inborn error of leucine metabolism that can cause significant morbidity and mortality. Since the implementation, in many states and countries, of newborn screening (NBS) by tandem mass spectrometry, IVA can now be diagnosed presymptomatically. Molecular genetic analysis of the IVD gene for 19 subjects whose condition was detected through NBS led to the identification of one recurring mutation, 932C-->T (A282V), in 47% of mutant alleles. Surprisingly, family studies identified six healthy older siblings with identical genotype and biochemical evidence of IVA. Our findings indicate the frequent occurrence of a novel mild and potentially asymptomatic phenotype of IVA. This has significant consequences for patient management and counseling.
Ensenauer
Regina
R
Department of Laboratory Medicine & Pathology, Division of Clinical Epidemiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. regina.ensenauer@med.uni-muenchen.de
Vockley
Jerry
J
Willard
Jan-Marie
JM
Huey
Joseph C
JC
Sass
Jörn Oliver
JO
Edland
Steven D
SD
Burton
Barbara K
BK
Berry
Susan A
SA
Santer
René
R
Grünert
Sarah
S
Koch
Hans-Georg
HG
Marquardt
Iris
I
Rinaldo
Piero
P
Hahn
Sihoun
S
Matern
Dietrich
D
D000465:Algorithms; D017931:DNA Primers; D005838:Genotype; D045782:Hemiterpenes; D006801:Humans; D007231:Infant, Newborn; D050769:Isovaleryl-CoA Dehydrogenase; D007930:Leucine / Q000378:metabolism*; D013058:Mass Spectrometry; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D015997:Neonatal Screening; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000172:deficiency* / Q000235:genetics*; D010421:Pentanoic Acids; D015183:Restriction Mapping
D017931:DNA Primers; D045782:Hemiterpenes; D010421:Pentanoic Acids; C008216:isovaleric acid; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050769:Isovaleryl-CoA Dehydrogenase; D007930:Leucine