Deficiency of the alkaline ceramidase ACER3 manifests in early childhood by progressive leukodystrophy.

ABSTRACT:

Background/aims

Leukodystrophies due to abnormal production of myelin cause extensive morbidity in early life; their genetic background is still largely unknown. We aimed at reaching a molecular diagnosis in Ashkenazi-Jewish patients who suffered from developmental regression at 6-13 months, leukodystrophy and peripheral neuropathy.

Methods

Exome analysis, determination of alkaline ceramidase activity catalysing the conversion of C18:1-ceramide to sphingosine and D-ribo-C12-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) (NBD)-phytoceramide to NBD-C12-fatty acid using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and thin layer chromatography, respectively, and sphingolipid analysis in patients' blood by LC-MS/MS.

Results

The patients were homozygous for p.E33G in t

SUBMITTER: Edvardson S 

PROVIDER: S-EPMC5068917 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature