Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD)

Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD)

We screened for the presence of inborn errors of metabolism (IEM) in 187 children (105 males; 82 females, ages 4–14 years old) who presented with confirmed features of autism spectrum disorder (ASD). Twelve patients (7%) manifested increased 3-hydroxyisovaleric acid (3-OH-IVA) excretion in urine, an...

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Main Authors: Spilioti, Martha, Evangeliou, Athanasios E., Tramma, Despoina, Theodoridou, Zoe, Metaxas, Spyridon, Michailidi, Eleni, Bonti, Eleni, Frysira, Helen, Haidopoulou, A., Asprangathou, Despoina, Tsalkidis, Aggelos J., Kardaras, Panagiotis, Wevers, Ron A., Jakobs, Cornelis, Gibson, K. Michael
Format: Online
Language:English
Published: Frontiers Media S.A. 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871708/
id pubmed-3871708
recordtype oai_dc
spelling pubmed-38717082014-01-07 Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD) Spilioti, Martha Evangeliou, Athanasios E. Tramma, Despoina Theodoridou, Zoe Metaxas, Spyridon Michailidi, Eleni Bonti, Eleni Frysira, Helen Haidopoulou, A. Asprangathou, Despoina Tsalkidis, Aggelos J. Kardaras, Panagiotis Wevers, Ron A. Jakobs, Cornelis Gibson, K. Michael Neuroscience We screened for the presence of inborn errors of metabolism (IEM) in 187 children (105 males; 82 females, ages 4–14 years old) who presented with confirmed features of autism spectrum disorder (ASD). Twelve patients (7%) manifested increased 3-hydroxyisovaleric acid (3-OH-IVA) excretion in urine, and minor to significant improvement in autistic features was observed in seven patients following supplementation with biotin. Five diagnoses included: Lesch Nyhan syndrome (2), succinic semialdehyde dehydrogenase (SSADH) deficiency (2), and phenylketonuria (1) (2.7%). Additional metabolic disturbances suggestive of IEMs included two patients whose increased urine 3-OH-IVA was accompanied by elevated methylcitrate and lactate in sera, and 30 patients that showed abnormal glucose-loading tests. In the latter group, 16/30 patients manifested increased sera beta hydroxybutyrate (b-OH-b) production and 18/30 had a paradoxical increase of sera lactate. Six patients with elevated b-OH-b in sera showed improved autistic features following implementation of a ketogenic diet (KD). Five patients showed decreased serum ketone body production with glucose loading. Twelve of 187 patients demonstrated non-specific MRI pathology, while 25/187 had abnormal electroencephalogram (EEG) findings. Finally, family history was positive for 22/187 patients (1st or 2nd degree relative with comparable symptomatology) and consanguinity was documented for 12/187 patients. Our data provide evidence for a new biomarker (3-OH-IVA) and novel treatment approaches in ASD patients. Concise 1 sentence take-home message: Detailed metabolic screening in a Greek cohort of ASD patients revealed biomarkers (urine 3-hydroxyisovaleric acid and serum b-OH-b) in 7% (13/187) of patients for whom biotin supplementation or institution of a KD resulted in mild to significant clinical improvement in autistic features. Frontiers Media S.A. 2013-12-24 /pmc/articles/PMC3871708/ /pubmed/24399946 http://dx.doi.org/10.3389/fnhum.2013.00858 Text en Copyright © 2013 Spilioti, Evangeliou, Tramma, Theodoridou, Metaxas, Michailidi, Bonti, Frysira, Haidopoulou, Asprangathou, Tsalkidis, Kardaras, Wevers, Jakobs and Gibson. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Spilioti, Martha
Evangeliou, Athanasios E.
Tramma, Despoina
Theodoridou, Zoe
Metaxas, Spyridon
Michailidi, Eleni
Bonti, Eleni
Frysira, Helen
Haidopoulou, A.
Asprangathou, Despoina
Tsalkidis, Aggelos J.
Kardaras, Panagiotis
Wevers, Ron A.
Jakobs, Cornelis
Gibson, K. Michael
spellingShingle Spilioti, Martha
Evangeliou, Athanasios E.
Tramma, Despoina
Theodoridou, Zoe
Metaxas, Spyridon
Michailidi, Eleni
Bonti, Eleni
Frysira, Helen
Haidopoulou, A.
Asprangathou, Despoina
Tsalkidis, Aggelos J.
Kardaras, Panagiotis
Wevers, Ron A.
Jakobs, Cornelis
Gibson, K. Michael
Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD)
author_facet Spilioti, Martha
Evangeliou, Athanasios E.
Tramma, Despoina
Theodoridou, Zoe
Metaxas, Spyridon
Michailidi, Eleni
Bonti, Eleni
Frysira, Helen
Haidopoulou, A.
Asprangathou, Despoina
Tsalkidis, Aggelos J.
Kardaras, Panagiotis
Wevers, Ron A.
Jakobs, Cornelis
Gibson, K. Michael
author_sort Spilioti, Martha
title Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD)
title_short Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD)
title_full Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD)
title_fullStr Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD)
title_full_unstemmed Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD)
title_sort evidence for treatable inborn errors of metabolism in a cohort of 187 greek patients with autism spectrum disorder (asd)
description We screened for the presence of inborn errors of metabolism (IEM) in 187 children (105 males; 82 females, ages 4–14 years old) who presented with confirmed features of autism spectrum disorder (ASD). Twelve patients (7%) manifested increased 3-hydroxyisovaleric acid (3-OH-IVA) excretion in urine, and minor to significant improvement in autistic features was observed in seven patients following supplementation with biotin. Five diagnoses included: Lesch Nyhan syndrome (2), succinic semialdehyde dehydrogenase (SSADH) deficiency (2), and phenylketonuria (1) (2.7%). Additional metabolic disturbances suggestive of IEMs included two patients whose increased urine 3-OH-IVA was accompanied by elevated methylcitrate and lactate in sera, and 30 patients that showed abnormal glucose-loading tests. In the latter group, 16/30 patients manifested increased sera beta hydroxybutyrate (b-OH-b) production and 18/30 had a paradoxical increase of sera lactate. Six patients with elevated b-OH-b in sera showed improved autistic features following implementation of a ketogenic diet (KD). Five patients showed decreased serum ketone body production with glucose loading. Twelve of 187 patients demonstrated non-specific MRI pathology, while 25/187 had abnormal electroencephalogram (EEG) findings. Finally, family history was positive for 22/187 patients (1st or 2nd degree relative with comparable symptomatology) and consanguinity was documented for 12/187 patients. Our data provide evidence for a new biomarker (3-OH-IVA) and novel treatment approaches in ASD patients. Concise 1 sentence take-home message: Detailed metabolic screening in a Greek cohort of ASD patients revealed biomarkers (urine 3-hydroxyisovaleric acid and serum b-OH-b) in 7% (13/187) of patients for whom biotin supplementation or institution of a KD resulted in mild to significant clinical improvement in autistic features.
publisher Frontiers Media S.A.
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871708/
_version_ 1612041077739487232

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