Biotin-responsive basal ganglia disease: a treatable differential diagnosis of Leigh syndrome

Distelmaier, Felix; Huppke, Peter; Schaper, Jutta; Morava, Éva; Mayatepek, Ertan; Kohlhase, Jürgen; Karenfort, Michael

doi:10.1055/s-0033-1337695

Cited by 2 publications

(2 citation statements)

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“…Biotin‐ or thiamine‐responsive encephalopathy type or thiamine metabolism dysfunction syndrome 2 (THMD2), formerly known as biotin responsive basal ganglia disease is an autosomal recessively inherited disease caused by mutations in thiamine transporter type 2 (ThTR‐2), encoded by SLC19A3 (#606152) . Phenotypes linked to SLC19A3 deficiency include Leigh encephalopathy and Wernicke encephalopathy . Yamada et al reported four Japanese patients who presented with epileptic spasms in early infancy, severe psychomotor retardation, brain atrophy, and bilateral thalamic and basal ganglia lesions.…”

Section: Inborn Errors Of Metabolism Leading To Thiamine Dysfunction mentioning

confidence: 99%

Genetic defects of thiamine transport and metabolism: A review of clinical phenotypes, genetics, and functional studies

Marcé‐Grau

Martí-Sánchez

Baide‐Mairena

et al. 2019

J of Inher Metab Disea

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Thiamine is a crucial cofactor involved in the maintenance of carbohydrate metabolism and participates in multiple cellular metabolic processes within the cytosol, mitochondria, and peroxisomes. Currently, four genetic defects have been described causing impairment of thiamine transport and metabolism: SLC19A2 dysfunction leads to diabetes mellitus, megaloblastic anemia and sensory‐neural hearing loss, whereas SLC19A3, SLC25A19, and TPK1‐related disorders result in recurrent encephalopathy, basal ganglia necrosis, generalized dystonia, severe disability, and early death. In order to achieve early diagnosis and treatment, biomarkers play an important role. SLC19A3 patients present a profound decrease of free‐thiamine in cerebrospinal fluid (CSF) and fibroblasts. TPK1 patients show decreased concentrations of thiamine pyrophosphate in blood and muscle. Thiamine supplementation has been shown to improve diabetes and anemia control in Rogers' syndrome patients due to SLC19A2 deficiency. In a significant number of patients with SLC19A3, thiamine improves clinical outcome and survival, and prevents further metabolic crisis. In SLC25A19 and TPK1 defects, thiamine has also led to clinical stabilization in single cases. Moreover, thiamine supplementation leads to normal concentrations of free‐thiamine in the CSF of SLC19A3 patients. Herein, we present a literature review of the current knowledge of the disease including related clinical phenotypes, treatment approaches, update of pathogenic variants, as well as in vitro and in vivo functional models that provide pathogenic evidence and propose mechanisms for thiamine deficiency in humans.

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Section: Inborn Errors Of Metabolism Leading To Thiamine Dysfunction mentioning

confidence: 99%

Genetic defects of thiamine transport and metabolism: A review of clinical phenotypes, genetics, and functional studies

Marcé‐Grau

Martí-Sánchez

Baide‐Mairena

et al. 2019

J of Inher Metab Disea

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“…Cogwheel rigidity is a classic feature, and parkinsonism may develop in untreated individuals . Brain imaging is often diagnostic and shows a “Leigh syndrome–like” pattern with central bilateral necrosis in the head of the caudate and putamen . Vasogenic edema is observed during the acute presentation whereas atrophy and gliosis in the affected regions are observed in chronic disease .…”

Section: The “Top Ten” Of Treatable Iems Presenting With Movement Dismentioning

confidence: 99%

Movement Disorders in Treatable Inborn Errors of Metabolism

Ebrahimi‐Fakhari

Karnebeek²,

Münchau

2018

Movement Disorders

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There are several hundred single‐gene disorders that we classify as inborn errors of metabolism. Inborn errors of metabolism are often rare and highly heterogeneous multisystem diseases with non‐neurological and neurological manifestations, commonly with onset during childhood. Movement disorders are among the most common neurological problems in inborn errors of metabolism, but, in many cases, remain poorly defined. Although movement disorders are usually not the only and often not the presenting symptom, their recognition can facilitate a diagnosis. Movement disorders contribute substantially to the morbidity in inborn errors of metabolism and can have a significant impact on quality of life. Common metabolic movement disorders include the monoamine neurotransmitter disorders, disorders of amino and organic acid metabolism, metal storage disorders, lysosomal storage disorders, congenital disorders of autophagy, disorders of creatine metabolism, vitamin‐responsive disorders, and disorders of energy metabolism. Importantly, disease‐modifying therapies exist for a number of inborn errors of metabolism, and early recognition and treatment can prevent irreversible CNS damage and reduce morbidity and mortality. A phenomenology‐based approach, based on the predominant movement disorder, can facilitate a differential diagnosis and can guide biochemical, molecular, and imaging testing. The complexity of metabolic movement disorders demands an interdisciplinary approach and close collaboration of pediatric neurologists, neurologists, geneticists, and experts in metabolism. In this review, we develop a general framework for a phenomenology‐based approach to movement disorders in inborn errors of metabolism and discuss an approach to identifying the “top ten” of treatable inborn errors of metabolism that present with movement disorders—diagnoses that should never be missed. © 2018 International Parkinson and Movement Disorder Society

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Biotin-responsive basal ganglia disease: a treatable differential diagnosis of Leigh syndrome

Cited by 2 publications

References 9 publications

Genetic defects of thiamine transport and metabolism: A review of clinical phenotypes, genetics, and functional studies

Genetic defects of thiamine transport and metabolism: A review of clinical phenotypes, genetics, and functional studies

Movement Disorders in Treatable Inborn Errors of Metabolism

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