ArticleMolecular genetics and metabolism
Prospective diagnosis of MT-ATP6-related mitochondrial disease by newborn screening.
Article in Molecular genetics and metabolism. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Evaluation of Newborn Screening for Diseases Using C5-OH as a Marker: Systematic Review of the Literature and Evaluation of 17 Years of C5-OH Screening in the Netherlands.Journal of inherited metabolic disease · 2025Pooled it
- Advances in diagnosis of mitochondrial dysfunction and primary mitochondrial disease.Disease models & mechanisms · 2026Review
- Advances in Primary Mitochondrial Diseases: Diagnosis, Natural History Studies and Clinical Trials.Genes · 2026Review
- MT-ATP6 9035T>C Variant Causes Ataxia With Azoospermia and Apparent Anticipation in a Four-generation Kindred.Cerebellum (London, England) · 2026Observational
- [Decreased plasma citrulline is a biochemical marker in newborn screening forZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Review
- Hypocitrullinemia as an Early Diagnostic Biomarker for MT-ATP6 Mitochondrial Diseases.Journal of molecular neuroscience : MN · 2025Article
- Natural History of Patients With Mitochondrial ATPase Deficiency Due to Pathogenic Variants of MT-ATP6 and MT-ATP8.Neurology · 2025Article
- Leigh Syndrome due toMolecular syndromology · 2024Article
- Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020-2023).International journal of neonatal screening · 2024Review
- Variants in Human ATP Synthase Mitochondrial Genes: Biochemical Dysfunctions, Associated Diseases, and Therapies.International journal of molecular sciences · 2024Review
- Article
- Select Ethical Aspects of Next-Generation Sequencing Tests for Newborn Screening and Diagnostic Evaluation of Critically Ill Newborns.International journal of neonatal screening · 2021Review
- [Leigh syndrome caused by the mitochondrial m.8993T>G mutation with hypocitrullinemia: a report of four cases and literature review].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatricsReview
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Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
Elevated citrulline and C5-OH levels are reported as part of the newborn screening of core and secondary disorders on the Recommended Uniform Screening Panel (RUSP). Additionally, some state laboratory newborn screening programs report low citrulline levels, which may be observed in proximal urea cycle disorders. We report six patients who were found on newborn screening to have low citrulline and/or elevated C5-OH levels in whom confirmatory testing showed the combination of these two abnormal analytes. Mitochondrial sequencing revealed known pathogenic variants in MT-ATP6 at high heteroplasmy levels in all cases. MT-ATP6 at these heteroplasmy levels is associated with Leigh syndrome, a progressive neurodegenerative disease. Patients were treated with supplemental citrulline and, in some cases, mitochondrial cofactor therapy. These six patients have not experienced metabolic crises or developmental regression, and early diagnosis and management may help prevent the neurological sequelae of Leigh syndrome. The affected mothers and siblings are asymptomatic or paucisymptomatic (e.g. intellectual disability, depression, migraines, obsessive-compulsive disorder, and poor balance) despite high heteroplasmy or apparent homoplasmy of the familial variant, thus expanding the clinical spectrum seen in pathogenic variants of MT-ATP6. Confirmatory plasma amino acid analysis and acylcarnitine profiling should be ordered in a patient with either low citrulline and/or elevated C5-OH, as this combination appears specific for pathogenic variants in MT-ATP6.
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Registered trials
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