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 ASD. Twelve patients (7%) manifested increased 3-hydroxyisovaleric acid (3-OH-IVA) excretion in urine, and minor to significant imp...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-12-01
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| Series: | Frontiers in Human Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnhum.2013.00858/full |
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| author | Martha eSpilioti Athanasios eEvangeliou Despoina eTramma Zoe eTheodoridou Spyridon eMetaxas Eleni eMichailidi Eleni eBonti Helen eFrysira Katerina eHaidopoulou Despoina eAsprangathou Aggelos eTsalkidis Panagiotis eKardaras Ron eWevers Cornelis eJakobs Michael eGibson |
| author_facet | Martha eSpilioti Athanasios eEvangeliou Despoina eTramma Zoe eTheodoridou Spyridon eMetaxas Eleni eMichailidi Eleni eBonti Helen eFrysira Katerina eHaidopoulou Despoina eAsprangathou Aggelos eTsalkidis Panagiotis eKardaras Ron eWevers Cornelis eJakobs Michael eGibson |
| author_sort | Martha eSpilioti |
| collection | DOAJ |
| 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 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. Five patients showed decreased serum ketone body production with glucose loading. Twelve of 187 patients demonstrated nonspecific MRI pathology, while 25/187 had abnormal 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 autismspectrum disorder (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 ketogenic diet resulted in mild to significant clinical improvement in autistic features. |
| first_indexed | 2024-04-13T21:03:00Z |
| format | Article |
| id | doaj.art-a6eef380ae7946dfb0db2e5e307f61e5 |
| institution | Directory Open Access Journal |
| issn | 1662-5161 |
| language | English |
| last_indexed | 2024-04-13T21:03:00Z |
| publishDate | 2013-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Human Neuroscience |
| spelling | doaj.art-a6eef380ae7946dfb0db2e5e307f61e52022-12-22T02:30:05ZengFrontiers Media S.A.Frontiers in Human Neuroscience1662-51612013-12-01710.3389/fnhum.2013.0085856636Evidence for Treatable Inborn Errors of Metabolism in a Cohort of 187 Greek Patients with Autism Spectrum Disorder (ASD)Martha eSpilioti0Athanasios eEvangeliou1Despoina eTramma2Zoe eTheodoridou3Spyridon eMetaxas4Eleni eMichailidi5Eleni eBonti6Helen eFrysira7Katerina eHaidopoulou8Despoina eAsprangathou9Aggelos eTsalkidis10Panagiotis eKardaras11Ron eWevers12Cornelis eJakobs13Michael eGibson14Aristotle University of Thessaloniki, AHEPA HospitalAristotle University of Thessaloniki, Papageorgiou HospitalAristotle University of Thessaloniki, Papageorgiou HospitalSt. Luke's HospitalAristotle University of Thessaloniki, Papageorgiou HospitalUniversity of Crete, Medical SchoolPapageorgiou HospitalAthens University Medical School, Agia Sophia Children’s HospitalAristotle University of Thessaloniki, Papageorgiou HospitalAristotle University of Thessaloniki, Papageorgiou HospitalMedical School, University of ThraceAristotle University of Thessaloniki, Hippokration HospitalRadboud University Nijmegen Medical CentreVU University Medical CenterSection of Clinical Pharmacology, College of Pharmacy, Washington State UniversityWe 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 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. Five patients showed decreased serum ketone body production with glucose loading. Twelve of 187 patients demonstrated nonspecific MRI pathology, while 25/187 had abnormal 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 autismspectrum disorder (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 ketogenic diet resulted in mild to significant clinical improvement in autistic features.http://journal.frontiersin.org/Journal/10.3389/fnhum.2013.00858/fullBiotinKetogenic DietautismInborn errors of metabolismphenylketonuria3-hydroxyisovaleric acid |
| spellingShingle | Martha eSpilioti Athanasios eEvangeliou Despoina eTramma Zoe eTheodoridou Spyridon eMetaxas Eleni eMichailidi Eleni eBonti Helen eFrysira Katerina eHaidopoulou Despoina eAsprangathou Aggelos eTsalkidis Panagiotis eKardaras Ron eWevers Cornelis eJakobs Michael eGibson Evidence for Treatable Inborn Errors of Metabolism in a Cohort of 187 Greek Patients with Autism Spectrum Disorder (ASD) Frontiers in Human Neuroscience Biotin Ketogenic Diet autism Inborn errors of metabolism phenylketonuria 3-hydroxyisovaleric acid |
| title | 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_short | 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 |
| topic | Biotin Ketogenic Diet autism Inborn errors of metabolism phenylketonuria 3-hydroxyisovaleric acid |
| url | http://journal.frontiersin.org/Journal/10.3389/fnhum.2013.00858/full |
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