A Scoping Review of Inborn Errors of Metabolism Causing Progressive Intellectual and Neurologic Deterioration (PIND)
Background: Progressive intellectual and neurological deterioration (PIND) is a rare but severe childhood disorder characterized by loss of intellectual or developmental abilities, and requires quick diagnosis to ensure timely treatment to prevent possible irreversible neurological damage. Inborn er...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-02-01
|
| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2019.01369/full |
| _version_ | 1819145636224696320 |
|---|---|
| author | Hilde A. G. Warmerdam Elise A. Termeulen-Ferreira Laura A. Tseng Jessica Y. Lee Agnies M. van Eeghen Agnies M. van Eeghen Carlos R. Ferreira Clara D. M. van Karnebeek Clara D. M. van Karnebeek |
| author_facet | Hilde A. G. Warmerdam Elise A. Termeulen-Ferreira Laura A. Tseng Jessica Y. Lee Agnies M. van Eeghen Agnies M. van Eeghen Carlos R. Ferreira Clara D. M. van Karnebeek Clara D. M. van Karnebeek |
| author_sort | Hilde A. G. Warmerdam |
| collection | DOAJ |
| description | Background: Progressive intellectual and neurological deterioration (PIND) is a rare but severe childhood disorder characterized by loss of intellectual or developmental abilities, and requires quick diagnosis to ensure timely treatment to prevent possible irreversible neurological damage. Inborn errors of metabolism (IEMs) constitute a group of more than 1,000 monogenic conditions in which the impairment of a biochemical pathway is intrinsic to the pathophysiology of the disease, resulting in either accumulation of toxic metabolites and/or shortage of energy and building blocks for the cells. Many IEMs are amenable to treatment with the potential to improve outcomes. With this literature review we aim to create an overview of IEMs presenting with PIND in children, to aid clinicians in accelerating the diagnostic process.Methods: We performed a PubMed search on IEMs presenting with PIND in individuals aged 0–18 years. We applied stringent selection criteria and subsequently derived information on encoding genes, pathways, clinical and biochemical signs and diagnostic tests from IEMbase (www.iembase.org) and other sources.Results: The PubMed search resulted in a total of 2,152 articles and a review of references added another 19 articles. After applying our selection criteria, a total of 85 IEMs presenting with PIND remained, of which 57 IEMs were reported in multiple unrelated cases and 28 in single families. For 44 IEMs (52%) diagnosis can be achieved through generally accessible metabolic blood and urine screening tests; the remainder requires enzymatic and/or genetic testing. Treatment targeting the underlying pathophysiology is available for 35 IEMs (41%). All treatment strategies are reported to achieve stabilization of deterioration, and a subset improved seizure control and/or neurodevelopment.Conclusions: We present the first comprehensive overview of IEMs presenting with PIND, and provide a structured approach to diagnosis and overview of treatability. Clearly IEMs constitute the largest group of genetic PIND conditions and have the advantage of detectable biomarkers as well as amenability to treatment. Thus, the clinician should keep IEMs at the forefront of the diagnostic workup of a child with PIND. With the ongoing discovery of new IEMs, expanded phenotypes, and novel treatment strategies, continuous updates to this work will be required. |
| first_indexed | 2024-12-22T13:01:11Z |
| format | Article |
| id | doaj.art-2a1cfd0458b74afe8e725d8e7ea8364e |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-22T13:01:11Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-2a1cfd0458b74afe8e725d8e7ea8364e2022-12-21T18:24:59ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-02-011010.3389/fneur.2019.01369483513A Scoping Review of Inborn Errors of Metabolism Causing Progressive Intellectual and Neurologic Deterioration (PIND)Hilde A. G. Warmerdam0Elise A. Termeulen-Ferreira1Laura A. Tseng2Jessica Y. Lee3Agnies M. van Eeghen4Agnies M. van Eeghen5Carlos R. Ferreira6Clara D. M. van Karnebeek7Clara D. M. van Karnebeek8Department of Pediatrics, Emma Children's Hospital, Amsterdam Gastroenterology and Metabolism, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, NetherlandsDepartment of Pediatrics, Emma Children's Hospital, Amsterdam Gastroenterology and Metabolism, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, NetherlandsDepartment of Pediatrics, Emma Children's Hospital, Amsterdam Gastroenterology and Metabolism, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, NetherlandsCentre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, CanadaDepartment of Pediatrics, Emma Children's Hospital, Amsterdam Gastroenterology and Metabolism, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, Netherlands's Heeren Loo Care Group, Amsterdam, NetherlandsNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United StatesDepartment of Pediatrics, Emma Children's Hospital, Amsterdam Gastroenterology and Metabolism, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, NetherlandsDepartment of Pediatrics, Radboud Centre for Mitochondrial Medicine, Radboud University Medical Centre, Nijmegen, NetherlandsBackground: Progressive intellectual and neurological deterioration (PIND) is a rare but severe childhood disorder characterized by loss of intellectual or developmental abilities, and requires quick diagnosis to ensure timely treatment to prevent possible irreversible neurological damage. Inborn errors of metabolism (IEMs) constitute a group of more than 1,000 monogenic conditions in which the impairment of a biochemical pathway is intrinsic to the pathophysiology of the disease, resulting in either accumulation of toxic metabolites and/or shortage of energy and building blocks for the cells. Many IEMs are amenable to treatment with the potential to improve outcomes. With this literature review we aim to create an overview of IEMs presenting with PIND in children, to aid clinicians in accelerating the diagnostic process.Methods: We performed a PubMed search on IEMs presenting with PIND in individuals aged 0–18 years. We applied stringent selection criteria and subsequently derived information on encoding genes, pathways, clinical and biochemical signs and diagnostic tests from IEMbase (www.iembase.org) and other sources.Results: The PubMed search resulted in a total of 2,152 articles and a review of references added another 19 articles. After applying our selection criteria, a total of 85 IEMs presenting with PIND remained, of which 57 IEMs were reported in multiple unrelated cases and 28 in single families. For 44 IEMs (52%) diagnosis can be achieved through generally accessible metabolic blood and urine screening tests; the remainder requires enzymatic and/or genetic testing. Treatment targeting the underlying pathophysiology is available for 35 IEMs (41%). All treatment strategies are reported to achieve stabilization of deterioration, and a subset improved seizure control and/or neurodevelopment.Conclusions: We present the first comprehensive overview of IEMs presenting with PIND, and provide a structured approach to diagnosis and overview of treatability. Clearly IEMs constitute the largest group of genetic PIND conditions and have the advantage of detectable biomarkers as well as amenability to treatment. Thus, the clinician should keep IEMs at the forefront of the diagnostic workup of a child with PIND. With the ongoing discovery of new IEMs, expanded phenotypes, and novel treatment strategies, continuous updates to this work will be required.https://www.frontiersin.org/article/10.3389/fneur.2019.01369/fullPINDinherited metabolic diseasesneurodegenerationdementialoss of skillsgenetic |
| spellingShingle | Hilde A. G. Warmerdam Elise A. Termeulen-Ferreira Laura A. Tseng Jessica Y. Lee Agnies M. van Eeghen Agnies M. van Eeghen Carlos R. Ferreira Clara D. M. van Karnebeek Clara D. M. van Karnebeek A Scoping Review of Inborn Errors of Metabolism Causing Progressive Intellectual and Neurologic Deterioration (PIND) Frontiers in Neurology PIND inherited metabolic diseases neurodegeneration dementia loss of skills genetic |
| title | A Scoping Review of Inborn Errors of Metabolism Causing Progressive Intellectual and Neurologic Deterioration (PIND) |
| title_full | A Scoping Review of Inborn Errors of Metabolism Causing Progressive Intellectual and Neurologic Deterioration (PIND) |
| title_fullStr | A Scoping Review of Inborn Errors of Metabolism Causing Progressive Intellectual and Neurologic Deterioration (PIND) |
| title_full_unstemmed | A Scoping Review of Inborn Errors of Metabolism Causing Progressive Intellectual and Neurologic Deterioration (PIND) |
| title_short | A Scoping Review of Inborn Errors of Metabolism Causing Progressive Intellectual and Neurologic Deterioration (PIND) |
| title_sort | scoping review of inborn errors of metabolism causing progressive intellectual and neurologic deterioration pind |
| topic | PIND inherited metabolic diseases neurodegeneration dementia loss of skills genetic |
| url | https://www.frontiersin.org/article/10.3389/fneur.2019.01369/full |
| work_keys_str_mv | AT hildeagwarmerdam ascopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT eliseatermeulenferreira ascopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT lauraatseng ascopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT jessicaylee ascopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT agniesmvaneeghen ascopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT agniesmvaneeghen ascopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT carlosrferreira ascopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT claradmvankarnebeek ascopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT claradmvankarnebeek ascopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT hildeagwarmerdam scopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT eliseatermeulenferreira scopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT lauraatseng scopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT jessicaylee scopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT agniesmvaneeghen scopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT agniesmvaneeghen scopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT carlosrferreira scopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT claradmvankarnebeek scopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind AT claradmvankarnebeek scopingreviewofinbornerrorsofmetabolismcausingprogressiveintellectualandneurologicdeteriorationpind |