Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023
Abstract Background Cerebral creatine deficiency disorders (CCDD) are rare diseases caused by defects in the enzymes L-arginine: glycine amidinotransferase (AGAT) or guanidinoacetate-N-methyltransferase (GAMT), which are involved in synthesis of creatine; or by a defect in the creatine transporter (...
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2025-01-01
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| Series: | Molecular and Cellular Pediatrics |
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| Online Access: | https://doi.org/10.1186/s40348-024-00188-4 |
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| author | Christina Kaufman Anaïs D’Andrea Annette Hackenberg Martin Poms Olivier Braissant Johannes Häberle |
| author_facet | Christina Kaufman Anaïs D’Andrea Annette Hackenberg Martin Poms Olivier Braissant Johannes Häberle |
| author_sort | Christina Kaufman |
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| description | Abstract Background Cerebral creatine deficiency disorders (CCDD) are rare diseases caused by defects in the enzymes L-arginine: glycine amidinotransferase (AGAT) or guanidinoacetate-N-methyltransferase (GAMT), which are involved in synthesis of creatine; or by a defect in the creatine transporter (CRTR), which is essential for uptake of creatine as important energy source into the target cells. Patients with CCDD can present with a variety of unspecific symptoms: global developmental delay, speech-language disorder, behavioral abnormalities and seizures. Early treatment initiation is essential in AGAT and GAMT deficiencies to achieve a favorable outcome. This study describes the CCDD patient cohort in a single center, and an analysis of the referrals to two Swiss laboratories in Lausanne and Zurich between 2015 and 2023 for the two marker metabolites guanidinoacetate and creatine. Results The patient cohort comprised 6 patients (defects: 2 GAMT, 4 CRTR), who were initially seen by different subspecialties depending on first symptoms. There was a diagnostic and therapeutic delay between 3 and 32 months (mean 13.8). Numbers of biomarker requests showed a constant increase during the study period, with a majority of tests performed in urine, the preferred sample for CCDD detection. Almost all samples (93.3%) were sent in by large hospitals (mainly from neurology, developmental pediatrics and metabolism) and only few (5.2%) by pediatricians in private practice, although those usually see the patients first. Conclusions The data from this study demonstrate a relevant delay in identifying patients with these rare conditions, and a predominance of biomarker analysis requested from pediatric subspecialties that are involved in patient management often long after occurrence of symptoms. To reduce the diagnostic delay and the outcome of patients, the current practice of sample referral should be reflected and first-contact healthcare providers should be encouraged to initiate selective screening. |
| format | Article |
| id | doaj-art-cfed738db3f347c2b97d0a185824c7eb |
| institution | Kabale University |
| issn | 2194-7791 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Molecular and Cellular Pediatrics |
| spelling | doaj-art-cfed738db3f347c2b97d0a185824c7eb2025-01-26T12:37:31ZengSpringerOpenMolecular and Cellular Pediatrics2194-77912025-01-011211810.1186/s40348-024-00188-4Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023Christina Kaufman0Anaïs D’Andrea1Annette Hackenberg2Martin Poms3Olivier Braissant4Johannes Häberle5Division of Metabolism and Children`s Research Center, University Children’s Hospital ZurichDivision of Metabolism and Children`s Research Center, University Children’s Hospital ZurichDivision of Pediatric Neurology, University Children’s Hospital ZurichDivision of Clinical Chemistry and Biochemistry, University Children’s Hospital ZurichService of Clinical Chemistry, University of Lausanne and Lausanne University HospitalDivision of Metabolism and Children`s Research Center, University Children’s Hospital ZurichAbstract Background Cerebral creatine deficiency disorders (CCDD) are rare diseases caused by defects in the enzymes L-arginine: glycine amidinotransferase (AGAT) or guanidinoacetate-N-methyltransferase (GAMT), which are involved in synthesis of creatine; or by a defect in the creatine transporter (CRTR), which is essential for uptake of creatine as important energy source into the target cells. Patients with CCDD can present with a variety of unspecific symptoms: global developmental delay, speech-language disorder, behavioral abnormalities and seizures. Early treatment initiation is essential in AGAT and GAMT deficiencies to achieve a favorable outcome. This study describes the CCDD patient cohort in a single center, and an analysis of the referrals to two Swiss laboratories in Lausanne and Zurich between 2015 and 2023 for the two marker metabolites guanidinoacetate and creatine. Results The patient cohort comprised 6 patients (defects: 2 GAMT, 4 CRTR), who were initially seen by different subspecialties depending on first symptoms. There was a diagnostic and therapeutic delay between 3 and 32 months (mean 13.8). Numbers of biomarker requests showed a constant increase during the study period, with a majority of tests performed in urine, the preferred sample for CCDD detection. Almost all samples (93.3%) were sent in by large hospitals (mainly from neurology, developmental pediatrics and metabolism) and only few (5.2%) by pediatricians in private practice, although those usually see the patients first. Conclusions The data from this study demonstrate a relevant delay in identifying patients with these rare conditions, and a predominance of biomarker analysis requested from pediatric subspecialties that are involved in patient management often long after occurrence of symptoms. To reduce the diagnostic delay and the outcome of patients, the current practice of sample referral should be reflected and first-contact healthcare providers should be encouraged to initiate selective screening.https://doi.org/10.1186/s40348-024-00188-4Cerebral creatine deficiencyDiagnostic delayExpressive speech delayGlobal developmental delayCognitive impairmentSubstitution therapy |
| spellingShingle | Christina Kaufman Anaïs D’Andrea Annette Hackenberg Martin Poms Olivier Braissant Johannes Häberle Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023 Molecular and Cellular Pediatrics Cerebral creatine deficiency Diagnostic delay Expressive speech delay Global developmental delay Cognitive impairment Substitution therapy |
| title | Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023 |
| title_full | Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023 |
| title_fullStr | Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023 |
| title_full_unstemmed | Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023 |
| title_short | Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023 |
| title_sort | diagnostic delay in cerebral creatine deficiency disorders lessons learned from a cross sectional single center study and guanidinoacetate and creatine measurements in switzerland between 2015 and 2023 |
| topic | Cerebral creatine deficiency Diagnostic delay Expressive speech delay Global developmental delay Cognitive impairment Substitution therapy |
| url | https://doi.org/10.1186/s40348-024-00188-4 |
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