Short-chain Acyl-CoA dehydrogenase deficiency: studies in a large family adding to the complexity of the disorder.
OBJECTIVE
To understand the expanding clinical and biochemical spectrum of short-chain acyl-CoA dehydrogenase (SCAD) deficiency, the impact of which is not fully understood.


METHODS
We studied a family with SCAD deficiency and determined urinary ethylmalonic acid excretion, plasma C(4)-carnitine, SCAD enzyme activity in fibroblasts and lymphocytes, DNA mutations in the SCAD gene, and clinical expression. The index patient was born prematurely and had otherwise unexplained cholestasis and hepatomegaly during the first year of life. His mother developed a hemolysis-elevated liver enzymes-low platelets (HELLP) syndrome while pregnant with the index patient.


RESULTS
Two siblings had a homozygous inactivating 1138C>T mutation, whereas the father was compound heterozygous for this mutation and the common 625G>A polymorphism. There was a good correlation between the type of SCAD mutation, the residual SCAD enzyme activity, and the levels of urinary ethylmalonic acid and plasma C(4)-carnitine in each of the eight family members. Retrospective acylcarnitine analysis of the index patient's Guthrie screening card confirmed the abnormal increase of C(4)-carnitine, suggestive of SCAD deficiency. None of the family members had hypotonia, developmental delay, or episodes of ketotic hypoglycemia.


CONCLUSIONS
Homozygosity for an inactivating SCAD mutation does not necessarily result in disease. The previously held opinion that SCAD deficiency is always a serious disorder may have been influenced by a clinical bias. Homozygosity for an inactivating 1138C>T SCAD mutation was assessed by neonatal screening of blood spot acylcarnitines. SCAD deficiency may be associated with maternal HELLP syndrome.
Bok
Levinus A
LA
Maxima Medisch Centrum, Veldhoven, The Netherlands.
Vreken
Peter
P
Wijburg
Frits A
FA
Wanders
Ronald J A
RJ
Gregersen
Niels
N
Corydon
Morten J
MJ
Waterham
Hans R
HR
Duran
Marinus
M
D019943:Amino Acid Substitution; D000743:Anemia, Hemolytic / Q000235:genetics; D044926:Butyryl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D002331:Carnitine / Q000097:blood; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008107:Liver Diseases / Q000235:genetics; D008297:Male; D008314:Malonates / Q000652:urine; D020125:Mutation, Missense; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011248:Pregnancy Complications; D013577:Syndrome; D013921:Thrombocytopenia / Q000235:genetics
D008314:Malonates; C038080:ethylmalonic acid; D044926:Butyryl-CoA Dehydrogenase; D002331:Carnitine