Recurrent vomiting and ethylmalonic aciduria associated with rare mutations of the short-chain acyl-CoA dehydrogenase gene.
We report identification of short-chain acyl-CoA dehydrogenase (SCAD) deficiency in a 12-year-old boy who suffered from recurrent attacks of vomiting once or twice a year from infancy. Growth and development were normal and there were no muscular symptoms. Metabolic screening was performed during a hospitalization at 8 years of age and revealed an increased excretion of ethylmalonic acid (EMA; 45-80 mmol/mol creatinine, normal 0.2-6.6), suggesting a degradation defect of short-chain fatty acids. An increased n-butyrylcarnitine was found in freshly collected serum (0.9 micromol/L; normal <0.4) but not in dry blood spots. Neither of the frequent SCAD gene variants 625G>A and 511C>T was present, but direct sequencing of the promoter and coding regions of the SCAD gene revealed that the patient had mutations on both alleles: 417G>C (Trpl15Cys) and 1095G>T (Gln341His). Neither mutation has been described before in compound heterozygosity or homozygosity. Enzymatic investigations subsequently confirmed a defect of SCAD in both fibroblasts and muscle extracts. Furthermore, expression studies of both mutations demonstrated impaired enzyme function or structure. To our knowledge, this case is the first description of a patient with proven SCAD deficiency presenting with recurrent emesis but without other symptoms, and emphasizes the wide clinical phenotype of this disorder.
Seidel
J
J
Department of Pediatrics, Friedrich-Schiller University, Jena, Germany. joerg.seidel@med.uni-jena.de
Streck
S
S
Bellstedt
K
K
Vianey-Saban
C
C
Pedersen
C B
CB
Vockley
J
J
Korall
H
H
Roskos
M
M
Deufel
T
T
Trefz
K F
KF
Sewell
A C
AC
Kauf
E
E
Zintl
F
F
Lehnert
W
W
Gregersen
N
N
D000483:Alleles; D044926:Butyryl-CoA Dehydrogenase / Q000235:genetics*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D005347:Fibroblasts; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008314:Malonates / Q000652:urine*; D018482:Muscle, Skeletal / Q000201:enzymology; D009154:Mutation / Q000235:genetics* / Q000502:physiology; D010084:Oxidation-Reduction; D010641:Phenotype; D012008:Recurrence; D014839:Vomiting / Q000209:etiology* / Q000235:genetics*
D018076:DNA, Complementary; D008314:Malonates; C038080:ethylmalonic acid; D044926:Butyryl-CoA Dehydrogenase