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Contiguous ABCD1 DXS1357E deletion syndrome: Report of an autopsy case
Author(s) -
Iwasa Mitsuaki,
Yamagata Takanori,
Mizuguchi Masashi,
Itoh Masayuki,
Matsumoto Ayumi,
Hironaka Mitsugu,
Honda Ayako,
Momoi Mariko Y.,
Shimozawa Nobuyuki
Publication year - 2013
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/j.1440-1789.2012.01348.x
Subject(s) - biology , pathology , cholestasis , exon , genetics , endocrinology , medicine , gene
Contiguous ABCD1 DXS1357E deletion syndrome ( CADDS ) is a contiguous deletion syndrome involving the ABCD1 and DXS1357E / BAP31 genes on Xq28 . Although ABCD1 is responsible for X ‐linked adrenoleukodystrophy ( X‐ALD ), its phenotype differs from that of CADDS , which manifests with many features of Zellweger syndrome ( ZS ), including severe growth and developmental retardation, liver dysfunction, cholestasis and early infantile death. We report here the fourth case of CADDS , in which a boy had dysmorphic features, including a flat orbital edge, hypoplastic nose, micrognathia, inguinal hernia, micropenis, cryptorchidism and club feet, all of which are shared by ZS . The patient achieved no developmental milestones and died of pneumonia at 8 months. Biochemical studies demonstrated abnormal metabolism of very long chain fatty acids, which was higher than that seen in X‐ALD . Immunocytochemistry and Western blot showed the absence of ALD protein ( ALDP ) despite the presence of other peroxisomal proteins. Pathological studies disclosed a small brain with hypomyelination and secondary hypoxic‐ischemic changes. Neuronal heterotopia in the white matter and leptomeningeal glioneuronal heterotopia indicated a neuronal migration disorder. The liver showed fibrosis and cholestasis. The thymus and adrenal glands were hypoplastic. Array comparative genomic hybridization ( CGH ) analysis suggested that the deletion was a genomic rearrangement in the 90‐kb span starting in DXS1357E / BACP31 exon 4 and included ABCD1 , PLXNB3 , SRPK3 , IDH3G and SSR4 , ending in PDZD4 exon 8. Thus, the absence of ALDP , when combined with defects in the B ‐cell antigen receptor associated protein 31 ( BAP31 ) and other factors, severely affects VLCFA metabolism on peroxisomal functions and produces ZS ‐like pathology.