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Treatable Leigh-like encephalopathy presenting in adolescence.

ABSTRACT: Wernicke's encephalopathy is a triad of ophthalmoplegia, ataxia and confusion seen in alcoholics with dietary vitamin B1 (thiamine) deficiency. A rare genetic defect of thiamine transporter-2 may lead to similar clinical features, biotin-thiamine responsive basal ganglia disease (BTBGD). A 15-year-old girl developed rapid onset ptosis and ophthalmoplegia evolving into a subacute encephalopathy. Neuroimaging demonstrated symmetrical basal ganglia and mid-brain lesions reminiscent of Leigh's subacute necrotising encephalomyelopathy. Oral biotin and thiamine were started, and symptoms improved dramatically the next day. The therapeutic response suggested SLC19A3, encoding thiamine transporter-2, as a strong candidate gene and Sanger sequencing revealed a novel homozygous c.517A>G;p.Asn173Asp mutation, which segregated with disease within the family. BTBGD is a potentially treatable neurological disorder and should be considered in the differential diagnosis of Leigh syndrome and Wernicke's encephalopathy. Since delayed treatment results in permanent neurological dysfunction or death, prompt diagnosis and early initiation of biotin and thiamine therapy are essential.

SUBMITTER: Fassone E

PROVIDER: S-EPMC3822156 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Treatable Leigh-like encephalopathy presenting in adolescence.

Fassone Elisa E Wedatilake Yehani Y DeVile Catherine J CJ Chong W Kling WK Carr Lucinda J LJ Rahman Shamima S

BMJ case reports 20131007

Wernicke's encephalopathy is a triad of ophthalmoplegia, ataxia and confusion seen in alcoholics with dietary vitamin B1 (thiamine) deficiency. A rare genetic defect of thiamine transporter-2 may lead to similar clinical features, biotin-thiamine responsive basal ganglia disease (BTBGD). A 15-year-old girl developed rapid onset ptosis and ophthalmoplegia evolving into a subacute encephalopathy. Neuroimaging demonstrated symmetrical basal ganglia and mid-brain lesions reminiscent of Leigh's subac ...[more]

PMID: 24099834

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Project description:ImportanceBiological aging is a distinct construct from health; however, people who age quickly are more likely to experience poor health. Identifying pediatric health conditions associated with accelerated aging could help develop treatment approaches to slow midlife aging and prevent poor health in later life.ObjectiveTo examine the association between 4 treatable health conditions in adolescence and accelerated aging at midlife.Design, setting, and participantsThis cohort study analyzed data from participants in the Dunedin Study, a longitudinal investigation of health and behavior among a birth cohort born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand, and followed up until age 45 years. Participants underwent an assessment at age 45 years and had data for at least 1 adolescent health condition (asthma, smoking, obesity, and psychological disorders) and outcome measure (pace of aging, gait speed, brain age, and facial age). Data analysis was performed from February 11 to September 27, 2021.ExposuresAsthma, cigarette smoking, obesity, and psychological disorders were assessed at age 11, 13, and 15 years.Main outcomes and measuresThe outcome was a midlife aging factor composite score comprising 4 measures of biological aging: pace of aging, gait speed, brain age (specifically, BrainAGE score), and facial age.ResultsA total of 910 participants (459 men [50.4%]) met the inclusion criteria, including an assessment at age 45 years. Participants who had smoked daily (0.61 [95% CI, 0.43-0.79] SD units), had obesity (0.82 [95% CI, 0.59-1.06] SD units), or had a psychological disorder diagnosis (0.43 [95% CI, 0.29-0.56] SD units) during adolescence were biologically older at midlife compared with participants without these conditions. Participants with asthma were not biologically older at midlife (0.02 [95% CI, -0.14 to 0.19] SD units) compared with those without asthma. These results remained unchanged after adjusting for childhood risk factors such as poor health, socioeconomic disadvantage, and adverse experiences.Conclusions and relevanceThis study found that adolescent smoking, obesity, and psychological disorder diagnoses were associated with older biological age at midlife. These health conditions could be treated during adolescence to reduce the risk of accelerated biological aging later in life.

Project description:3-Hydroxyisobutyryl-CoA hydrolase (HIBCH, NM_014362.3) gene mutation can cause HIBCH deficiency, leading to Leigh/Leigh-like disease. To date, few case series have investigated the relationship between metabolites and clinical phenotypes or the effects of treatment, although 34 patients with HIBCH mutations from 27 families have been reported. The purpose of this study was to analyze the phenotypic spectrum, follow-up results, metabolites, and genotypes of patients with HIBCH deficiency presenting with Leigh/Leigh-like syndrome and explore specific metabolites related to disease diagnosis and prognosis through retrospective and longitudinal studies. Applying next-generation sequencing, we identified eight patients with HIBCH mutations from our cohort of 181 cases of genetically diagnosed Leigh/Leigh-like syndrome. Six novel HIBCH mutations were identified: c.977T>G [p.Leu326Arg], c.1036G>T [p.Val346Phe], c.750+1G>A, c.810-2A>C, c.469C>T [p.Arg157*], and c.236delC [p.Pro79Leufs*5]. The Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) was employed to assess disease progression and clinical outcomes. The non-invasive approach of metabolite analysis showed that levels of some were associated with clinical phenotype severity. Five (5/7) patients presented with elevated C4-OH in dried blood spots, and the level was probably correlated with the NPMDS scores during the peak disease phase. 2,3-Dihydroxy-2-methylbutyrate in urine was elevated in six (6/7) patients and elevated S-(2-caboxypropyl)cysteamine in urine was found in three patients (3/3). The median age at initial presentation was 13 months (8-18 months), and the median follow-up was 2.3 years (range 1.3-7.2 years). We summarized and compared with all reported patients with HIBCH mutations. The most prominent clinical manifestations were developmental regression/delay, hypotonia, encephalopathy, and feeding difficulties. We administered drug and dietary treatment. During follow-up, five patients responded positively to treatment with a significant decrease in NPMDS scores. Our research is the largest case series of patients with HIBCH mutations.

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Treatable Leigh-like encephalopathy presenting in adolescence.

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Treatable Leigh-like encephalopathy presenting in adolescence.

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