31 July 2024: Articles
Distinct Imaging Markers of Leigh’s Disease Linked to Mutation: A Pediatric Case Study
Challenging differential diagnosis, Rare disease
Rama Krishna Narra1ABCDEFG*, Reshma Vemuri2BCDOI: 10.12659/AJCR.944514
Am J Case Rep 2024; 25:e944514
Abstract
BACKGROUND: Leigh disease (LD) is a rare progressive mitochondrial neurodegenerative disorder characterized by subacute necrotizing encephalopathy and symmetrical spongiform lesions in the brain. Cytochrome C oxidase deficiencies due to SURF1 Cytochrome C Oxidase Assembly Factor (SURF1) gene mutations are seen only in 15% of LD cases. Consideration of these genetic mutations in young patients is crucial for early diagnosis, intervention, and further genetic counseling. Although only a few cases of the SURF1 mutation have been reported, there are anecdotal case reports describing imaging features.
CASE REPORT: We report a case of a 2-year-old boy with developmental delay, hypotonia, involuntary movements, shortness of breath, and reduced activity since age 6 months. On blood examination there was mildly elevated lactate levels and increased lactate to pyruvate ratio and cerebrospinal fluid lactate levels. Magnetic resonance imaging findings showed symmetrical lesions in the dentate nucleus, subthalamic nucleus, midbrain (substantia nigra, periaqueductal gray matter), posterolateral pons, and olivary nucleus of the medulla extending into the cervical spinal cord, with mild elevation of the lactate peak on magnetic resonance spectroscopy.
CONCLUSIONS: These findings prompted further genetic analysis, which indicated a mitochondrial type IV deficiency with the SURF1 gene defect, an intranuclear type 1 mutation (MC4DN1) (OMIM 220110). Treatment is usually supportive with vitamins supplementation and physiotherapy, and genetic counseling of the parents is mandatory.
Keywords: Leigh disease, SURF1 Mutation, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Diffusion-weighted imaging, Apparent diffusion coefficient, Humans, Leigh disease, Male, Child, Preschool, Membrane Proteins, Mitochondrial Proteins, Magnetic Resonance Imaging, Mutation, Brain
Introduction
Leigh disease (LD) is a genetic disorder that is commonly inherited with an autosomal recessive pattern and homogeneous or compound heterogeneous genetic mutation defects. The most common gene mutations associated with LD are located in the mitochondrial DNA [1]. However, nuclear mutations result in rare Cytochrome C Oxidase Assembly Factor
Case Report
A 2-year-old first born male child born at term to consanguineous parents presented with developmental delay, hypotonia, involuntary movements, and shortness of breath, with reduced activity since age 6 months. The family history was insignificant, with no similar cases noted. The generalized symmetrical hypotonia showed markedly reduced deep tendon reflexes.
Laboratory investigations revealed mildly elevated blood lactate levels (37 mg/dL; normal 10–24 mg/dL) at rest with an increased lactate-o -pyruvate ratio of 35.9 (normal: 10–20). Cerebrospinal fluid analysis showed a mild increase in lactate levels.
On MRI of the brain, symmetrical hyperintense lesions were observed in the posterior lentiform nucleus, subthalamic nucleus, midbrain (substantia nigra, periaqueductal gray matter), posterolateral pons, and olivary nucleus of the medulla, extending into the cervical cord and bilateral dentate nucleus of the cerebellum on T2-weighted (T2W) MRI (Figure 1A–1F), with corresponding areas of non-enhancing hypointensities on T1-weighted (T1W) MRI (Figure 2A–2D). Diffusion-weighted MRI showed areas of restriction with a reduced apparent diffusion coefficient (ADC) in the periphery and within the lesion (Figure 3A, 3B). Magnetic resonance spectroscopy (MRS) demonstrated elevated choline, reduced N-acetylaspartate, and mild prominence of the lactate peak (Figure 4). Further targeted gene sequencing showed defects in the
The patient was given supportive treatment with Co-enzyme A, L-carnitine, thiamine, biotin, and other vitamin supplementation, and the child’s parents were advised to return for follow-up care. On follow-up there was slight improvement in the tone and involuntary movements and breathing of the patient.
Discussion
LD (aka subacute necrotizing encephalopathy) is a rare progressive neurodegenerative disorder characterized by symmetrical spongiform lesions in the brain. The disorder is caused by mitochondrial mutation, whereas the
Conclusions
LD is a rare metabolic neurodegenerative disease with spongiform degeneration in the brain. The possibility of a
Figures
References:
1.. Finsterer J, Inherited mitochondrial neuropathies: J Neurol Sci, 2011; 304; 9-16
2.. Kose M, Canda E, Kagnici M: Mol Genet Metab Rep, 2020; 25; 100657
3.. Arii J, Tanabe Y, Leigh syndrome: Serial MR imaging and clinical follow-up: Am J Neuroradiology, 2000; 21; 1502-9
4.. Miyauchi A, Osaka H, Nagashima M: Brain Dev, 2018; 40; 498-502
5.. Farina L, Chiapparini L, Uziel G: Am J Neuroradiology, 2003; 23; 1095-100
6.. Alves CAPF, Teixeira SR, Martin-Saavedra JS, Pediatric Leigh syndrome: Neuroimaging features and genetic correlations: Ann Neurol, 2020; 88; 218-32
7.. Rossi A, Biancheri R, Bruno C: Am J Neuroradiology, 2003; 24; 1188-91
8.. Lee IC, Chiang KL: Antioxidants (Basel), 2021; 10; 1950
Figures
In Press
Case report
Am J Case Rep In Press; DOI: 10.12659/AJCR.945539
Case report
Am J Case Rep In Press; DOI: 10.12659/AJCR.945795
Case report
Am J Case Rep In Press; DOI: 10.12659/AJCR.946588
Case report
Am J Case Rep In Press; DOI: 10.12659/AJCR.946011
Most Viewed Current Articles
21 Jun 2024 : Case report
88,761
DOI :10.12659/AJCR.944371
Am J Case Rep 2024; 25:e944371
07 Mar 2024 : Case report
50,081
DOI :10.12659/AJCR.943133
Am J Case Rep 2024; 25:e943133
20 Nov 2023 : Case report
25,336
DOI :10.12659/AJCR.941424
Am J Case Rep 2023; 24:e941424
18 Feb 2024 : Case report
22,657
DOI :10.12659/AJCR.943030
Am J Case Rep 2024; 25:e943030