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Carnitine‐palmitoyltransferase 2 deficiency: Novel mutations and relevance of newborn screening
Author(s) -
Illsinger Sabine,
Lücke Thomas,
Peter Michael,
Ruiter Jos P.N.,
Wanders Ronald J.A.,
Deschauer Marcus,
Handig Ingrid,
Wuyts Wim,
Das Anibh M.
Publication year - 2008
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.32545
Subject(s) - newborn screening , missense mutation , carnitine , beta oxidation , asymptomatic , medicine , endocrinology , compound heterozygosity , carnitine o palmitoyltransferase , exon , chemistry , biochemistry , mutation , gene , metabolism
We report on a newborn male, born at term after an uneventful pregnancy presenting with a pathological acylcarnitine profile in routine newborn screening on the third day of life. The profile showed characteristic elevations of C14:0‐, C16:0‐, C16:1‐ and C18:1‐acylcarnitines, while the ratio of (C16 + C18:1)/C2 was increased, suggesting CPT2‐ or carnitine‐acylcarnitine‐translocase‐ deficiency. The acylcarnitine profile in blood taken on day 9 was normal with breast milk feeding. No dicarboxylic aciduria was found. In fibroblasts, the activity of CPT2 was decreased to 25%, overall oxidation of the long‐chain fatty acids was reduced to 10% of control values. Sequence analysis of the CPT2 gene showed heterozygosity for two previously undescribed mutations in exon 4: c.748‐749delAA (truncating), and c.1436A > G (p.Tyr479Cys; missense) mutations. The asymptomatic parents were found to be heterozygous, the mother carries the c.748‐749delAA and the father the c.1436A > G mutation. The boy is now 2.5 years old; no clinical symptoms associated with the marked impairment of long‐chain fatty acid oxidation have occurred. Confirmation of mitochondrial fatty acid oxidation defects from an initial abnormal newborn‐screening by tandem mass spectrometry should include enzyme and, if possible, molecular genetic analysis despite a normal 2nd screening. Biochemical testing of urine (organic acids) may be unrevealing. © 2008 Wiley‐Liss, Inc.