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Indian Pediatr 2016;53: 263 |
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A Novel Missense Mutation in Very Long-chain
Acyl-CoA Dehydrogenase Deficiency
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#Qingting Bu and *Zhenyu Pan
#Department of Genetics, Northwest Women’s and
Children’s Hospital, No.1616 Yanxiang Road and *Department of Clinical
Pharmacy, Xi’an Jiaotong University Affiliated Children’s Hospital,
No.69 Xijuyuan Road, Xi’an, China.
Email: [email protected]
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Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a rare
disease [1], and may cause sudden death in infants if undiagnosed [2].
The molecular basis of VLCADD is complicated, with about one hundred
mutations reported. VLCADD can now be detected through newborn screening
(NBS). Sequence analysis of ACADVL, the gene for VLCAD, is used
to confirm the diagnosis of VLCADD.
The proband, a girl, was born at 40 weeks of
gestation following an uncomplicated pregnancy. Her NBS was performed at
14 days of age in our facility. The result was positive for VLCADD, with
a elevated c14:1 level of 4.38 µmol/L
(normal, 0.02 to 0.19 µmol/L).
Subsequent acylcarnitine profile in a new dried blood spot was tested
again by tandom mass spectrometry, and the organic acid profile in urea
was tested by gas chromotography mass spectrometry. The samples were
sent to a commercial laboratory where the following levels were
described: c14:1 of 2.75 µmol/L
(normal, 0.02 to 0.25 µmol/L),
adipic acid of 114.9 (normal, 0.5 to 5.0), pimelic acid of 24.3 (normal,
0.0 to 9.3), suberic acid of 69.7 (normal, 0.3 to 4.7) and 3-hydroxy
sebacic acid of 51.7 (normal, 0.0 to 4.4). During this period, she
developed feeding and vomiting. In the evening, her parents found her
drowsy in her crib. Combined with laboratory investigations, she was
diagnosed with alveobronchiolitis, bloodstream infection, and inherited
metabolic disease.
VLCAD gene sequencing of the proband revealed
compound heterozygous for the c.1843C>T (p.Arg615*) null mutation and
another novel mutation, c.1292A>G (p.Asp431Gly) on the other allele.
Targeted mutational analyses were also studied for all family members.
Her mother was heterozygous for c.1843C>T (p.Arg615*) and her father was
heterozygous for c.1292A>G (p.Asp431Gly). Because VLCADD is an autosomal
recessive inherited disease [3,4], this case indicates the ACADVL
c.1292A>G (p.Asp431Gly) might be a disease-causing mutation in human. In
summary, it is essential to find and summarize new mutations in future
clinical work because of the diversity of ACADVL mutations to
provide a theoretical basis for clinical diagnosis.
Acknowledgment: Dr. Rong Qiang.
Funding: Health Bureau of Xi’an
(No.QFO1330). Competing interests: None stated.
References
1 Arnold GL, Van Hove J, Freedenberg D, Strauss A,
Longo N, Burton B, et al. A delphi clinical practice protocol for
the management of very long chain acyl-coA dehydrogenase deficiency. Mol
Genet Metab. 2009;96:85-90.
2. Coughlin CR 2nd, Ficicioglu C. Genotype-phenotype
correlations: sudden death in an infant with very-long-chain acyl-CoA
dehydrogenase deficiency. J Inherit Metab Dis. 2010;33:129-31.
3. Yamaguchi S, Indo Y, Coates PM, Hashimoto T,
Tanaka K. Identiûcation of very long chain acyl-CoA dehydrogenase
deûciency in three patients previously diagnosed with long-chain
acyl-CoA dehydrogenase deûciency. Pediatr Res. 1993;34:111-3.
4. Aoyama T, Uchida Y, Kelley RI, Marble M, Hofman K,
Tonsgard JH, et al. A novel disease with deficiency of
mitochondrial very-long-chain acyl-CoA dehydrogenase. Biochem Biophys
Res Commun. 1993;191:1369-72.
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