Abstract
We report on a 6โyearโold girl who presented at 6 months of age with seizures, delayed psychomotor development and mild facial dysmorphism. A small muscular ventricular septal defect was documented on echocardiogram and brain MRI showed a frontal brain anomaly. Urine organic acid analysis revealed dicarboxylic aciduria, and plasma acylcarnitine analysis showed marked elevation of octanoyl (C8) and decanoyl (C10) carnitines with C8:C10 ratio of 9:1. These results were indicative of medium chain acylโCoA dehydrogenase deficiency. ACADM gene sequencing showed an apparent homozygous c.166Gโ>โC (Ala31Pro) missense mutation in exon 3; however, only the mother was found to be a carrier of this novel missense mutation. This finding along with nonโregressive developmental delay prompted further karyotype and genomic investigations. An interstitial deletion of chromosome 1 was detected by repeat Gโbanding: 46,XX,del(1)(p22.2p31.1). Parental karyotypes were normal. The deletion was characterized by array CGH analysis using a 1 Mb BAC/PAC array platform. Clones deleted extended from RP11โ88B10 (1p31.1) to RP5โ1007M22 (1p22.2), a 15.5 Mb deletion which includes the ACADM locus. Clinical review of 6/7 cases of interstitial deletions with breakpoints of 1p22 and 1p31/32, including the patient in this report, indicate a variable phenotype. Thus, although Gโband breakpoints are similar, common breakpoints for these alterations are unlikely. This is the first report of a patient with fatty acid oxidation defect caused by a mutation in combination with an interstitial chromosomal deletion. ยฉ 2008 WileyโLiss, Inc.