A review of the results of the very long chain fatty acid analyses for X-linked Adrenoleukodystrophy at the Biochemical Genetics Laboratory of the Institute of Human Genetics-National Institutes of Health, Manila

@#Background. X-linked adrenoleukodystrophy (X-ALD) is a progressive genetic disorder affecting the metabolism of very long chain fatty acids in the adrenal glands, spinal cord and white matter of the nervous system. It is an inherited metabolic storage disease whereby a defect in a specific enzyme results in the accumulation of very long-chain fatty acids (VLCFA) that are harmful to some cells and organs. VLCFA analysis for confirmation of X-linked adrenoleukodystrophy is one of the most requested tests among the send-out laboratory services of the Biochemical Genetics Laboratory at the Institute of Human Genetics. This paper aims to review the clinical characteristics and the results of the VLCFA analysis of the patients whose samples we received for testing.Methods. Overseas tests samples received by the Biochemical Genetics Laboratory for VLCFA from 2002-2016 were included. The details of the patients were collated in an overseas tests database and was the main source of the data for this study. The results of the VLCFA tests sent to the Kennedy Krieger Institute and The Children’s Hospital at Westmead were inputted into the said database. Descriptive statistics was utilized in order to examine the clinical and biochemical data of the patients.Results. The results showed that out of the 54 samples submitted to our laboratory, 19 (35%) of the samples received from male patients suspected to have X-ALD yielded positive results and another 10 (19%) females were found to be carriers. Visual defect followed by deteriorating mental status were the most frequent indications for VLCFA testing. Conclusion. Having a significant diagnostic yield of 54%, early diagnosis of X-linked adrenoleukodystrophy in our population is important so that proper management that could prevent the progression of the disease could be timely instituted.

Fatty acid composition of Drosophila photoreceptor light-sensitive microvilli

Phototransduction, the mechanism underlying the electrical response to light in photoreceptor cells, has been thoroughly investigated in Drosophila melanogaster, an essential model in signal transduction research. These cells present a highly specialized photosensitive membrane consisting of thousands of microvilli forming a prominent structure termed a rhabdomere. These microvilli encompass the phototransduction proteins, most of which are transmembrane and exclusively rhabdomeric. Rhabdomere membrane lipids play a crucial role in the activation of the transient receptor potential ionic channels (TRP and TRPL) responsible for initiating the photoresponse. Despite its importance, rhabdomere lipid composition has not been established. We developed a novel preparation enriched in rhabdomere membranes to perform a thorough characterization of the lipidomics of Drosophila rhabdomeres. Isolated eyes (500) were homogenized and subjected to a differential centrifugation protocol that generates a fraction enriched in rhabdomere membrane. Lipids extracted from this preparation were identified and quantified by gas chromatography coupled to mass spectrometry. We found an abundance of low sterol esters (C16:0, C18:0), highly abundant and diverse triglycerides, free fatty acids, a moderate variety of mono and diacyglycerols (C:16:0, 18:0, C18:1) and abundant phospholipids (principally C18:2). This preparation opens a new avenue for investigating essential aspects of phototransduction.