Case report: Aqueous and Vitreous amino-acid concentrations in a patient with maple syrup urine disease operated on rhegmatogenous retinal detachment

BMC Ophthalmology, Oct 2016

Background Maple syrup urine disease (MSUD) is a rare metabolic disorder, affecting the metabolism of branched chain amino-acids (Valine, Leukine, Isoleukine). We present a rare case of rhegmatogenous retinal detachment (RRD) in a MSUD patient. Case presentation We performed amino acid analysis of aqueous humour, vitreous and serum samples obtained during surgery from a 24 year old female MSUD patient successfully operated on RRD. Serum values for a-amino-butyric acid, valine, isoleucine, leucine, tyrosine, phenylalanine, ornithine and histidine were low, while values for citrulline, methionine and lysine were borderline low, all attributed to the patient’s special diet. Serum glutamate was above normal, probably due to the breakdown of glutamine to glutamate. In the aqueous and vitreous the amino acids implicated in MSUD (Valine, Leukine Isoleukine), were within normal range. Glutamate was absent in the vitreous and presented low levels in the aqueous. Glutamate has been reported to play an important role in retinal damage. Elevated glutamate levels have been reported in vitreous specimens from patients subjected to vitrectomy or buckling surgery for RRD. In MSUD, glutamate has been implicated in the pathogenesis of brain damage. Low levels of glutamate have been observed in the cerebellum of experimental MSUD animals, as well as postmortem brain tissue from a child that died of leucine intoxication. The reduction was attributed to the elevation of a-ketoisocaproic which reverses the net direction of nitrogen flow. It could be argued that this could impact on amino acid concentration in aqueous and vitreous fluids. Conclusions Although no definite conclusions can be drawn by this extremely rare case, the low vitreous and aqueous levels of Glutamate is an interesting finding. Further studies are needed to provide a better insight in the role of amino acids as neurotransmitters in the human eye in health and disease.

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Case report: Aqueous and Vitreous amino-acid concentrations in a patient with maple syrup urine disease operated on rhegmatogenous retinal detachment

Kanakis et al. BMC Ophthalmology Case report: Aqueous and Vitreous amino- acid concentrations in a patient with maple syrup urine disease operated on rhegmatogenous retinal detachment Menelaos G. Kanakis 0 Helen Michelakakis 1 Petros Petrou 0 Chrysanthi Koutsandrea 0 Ilias Georgalas 0 0 1st Department of Ophthalmology, “G. Gennimatas” Hospital of Athens, National and Kapodistrian University of Athens , Mesogeion 154, Athens 11527 , Greece 1 Department Enzymology and Cellular Function, Institute of Child Health , 7 Fokidos street, Athens 11526 , Greece Background: Maple syrup urine disease (MSUD) is a rare metabolic disorder, affecting the metabolism of branched chain amino-acids (Valine, Leukine, Isoleukine). We present a rare case of rhegmatogenous retinal detachment (RRD) in a MSUD patient. Case presentation: We performed amino acid analysis of aqueous humour, vitreous and serum samples obtained during surgery from a 24 year old female MSUD patient successfully operated on RRD. Serum values for a-amino-butyric acid, valine, isoleucine, leucine, tyrosine, phenylalanine, ornithine and histidine were low, while values for citrulline, methionine and lysine were borderline low, all attributed to the patient's special diet. Serum glutamate was above normal, probably due to the breakdown of glutamine to glutamate. In the aqueous and vitreous the amino acids implicated in MSUD (Valine, Leukine Isoleukine), were within normal range. Glutamate was absent in the vitreous and presented low levels in the aqueous. Glutamate has been reported to play an important role in retinal damage. Elevated glutamate levels have been reported in vitreous specimens from patients subjected to vitrectomy or buckling surgery for RRD. In MSUD, glutamate has been implicated in the pathogenesis of brain damage. Low levels of glutamate have been observed in the cerebellum of experimental MSUD animals, as well as postmortem brain tissue from a child that died of leucine intoxication. The reduction was attributed to the elevation of a-ketoisocaproic which reverses the net direction of nitrogen flow. It could be argued that this could impact on amino acid concentration in aqueous and vitreous fluids. Conclusions: Although no definite conclusions can be drawn by this extremely rare case, the low vitreous and aqueous levels of Glutamate is an interesting finding. Further studies are needed to provide a better insight in the role of amino acids as neurotransmitters in the human eye in health and disease. Case report; Maple syrup urine disease; Retinal detachment; Amino acid concentration; Vitreous - Background MSUD is a rare (1:200,000) genetic metabolic disease, caused by a defect in branched chain ketoacid dehydrogenase (BCKA), leading to elevated concentrations of the branched-chain amino acids leucine, isoleucine, and valine [1]. This enzyme is a supra enzyme complex consisting of multiple copies of four distinct subunits and is located in the inner wall of the mitochondrion. The disease has autosomal-recessive inheritance. Ocular complications of untreated disease or late diagnosis include optic atrophy, nystagmus, ophthalmoplegia, strabismus, and cortical blindness [2]. Case presentation A 24 year old Caucasian female was admitted to our hospital when diagnosed with Rhegmatogenous Retinal Detachment (RRD), on her left eye. The patient also suffers from maple syrup urine disease (MSUD), for which © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. she has been maintained on a special diet and thiamine supplements, autismus (under treatment with quetiapine, oxcarbazepine and fluvoxamine), and ulcerative colitis (under treatment with mesalamine) (Table 1) (Additional file 1). Dilated fundus examination revealed an inferior retinal detachment (3 – 8th h), macula off. The detachment had been discovered 12 days ago and there were not any signs of Proliferative vitreoretinopathy (PVR). The patient was operated on successfully under general anesthesia, with 23G Vitrectomy (Constellation Vitrectomy System, Alcon Laboratories, Texas, USA), and is under follow up for the last four months. Apart from the successfully treated retinal detachment, slit lamp biomicroscopy and fundus examination were unremarkable on admission and during the follow up period. Informed consent of the custodian (mother) was obtained, since the patient is mentally retarded due to MSUD. Undiluted vitrectomy samples (approx (...truncated)


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Menelaos Kanakis, Helen Michelakakis, Petros Petrou, Chrysanthi Koutsandrea, Ilias Georgalas. Case report: Aqueous and Vitreous amino-acid concentrations in a patient with maple syrup urine disease operated on rhegmatogenous retinal detachment, BMC Ophthalmology, 2016, pp. 170, 16, DOI: 10.1186/s12886-016-0349-3