Decreased plasma citrulline is a biochemical marker in newborn screening for MT-ATP6-associated mitochondrial disease: two case reports and a literature review

Hui-Ming YAN; Ying QUAN; Ying ZHOU; Luo JIANG; Liang-Yu ZHANG; Zheng-Qing WAN; Hui XI

doi:10.7499/j.issn.1008-8830.2505143

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Chinese Journal of Contemporary Pediatrics ›› 2026, Vol. 28 ›› Issue (2) : 250-256. DOI: 10.7499/j.issn.1008-8830.2505143

RARE DISEASE RESEARCH

Decreased plasma citrulline is a biochemical marker in newborn screening for MT-ATP6-associated mitochondrial disease: two case reports and a literature review

Hui-Ming YAN ¹^,² ,
Ying QUAN ⁴ ,
Ying ZHOU ¹^,² ,
Luo JIANG ³ ,
Liang-Yu ZHANG ¹ ,
Zheng-Qing WAN ¹^,² ,
Hui XI ¹^,²

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Abstract

This report describes the potential diagnostic value of decreased plasma citrulline (pCit) levels for the early recognition of MT-ATP6-related mitochondrial disease. Two cases were reported, and relevant literature was reviewed. Case 1: Onset occurred at 3 months of age with an acute presentation that rapidly progressed to metabolic crisis, multiorgan failure, and central respiratory failure, resulting in death in early infancy. Case 2: Onset occurred at 6 months of age with progressive developmental delay. Brain magnetic resonance imaging revealed bilateral symmetric basal ganglia lesions, and Leigh syndrome was diagnosed. Following citrulline supplementation and comprehensive intervention, improvements were observed in intellectual development and metabolic indices. Both patients carried the MT-ATP6 variant m.8993T>G (p.L156R), confirming MT-ATP6-associated mitochondrial disease. This case series indicates that decreased pCit on newborn screening is an early biochemical marker of MT-ATP6-associated mitochondrial disease. Early diagnosis and metabolic intervention are beneficial for prognosis.

Key words

Mitochondrial disease / MT-ATP6 / m.8993T>G / Hypocitrullinemia / Newborn screening

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Hui-Ming YAN , Ying QUAN , Ying ZHOU , et al . Decreased plasma citrulline is a biochemical marker in newborn screening for MT-ATP6-associated mitochondrial disease: two case reports and a literature review[J]. Chinese Journal of Contemporary Pediatrics. 2026, 28(2): 250-256 https://doi.org/10.7499/j.issn.1008-8830.2505143

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