Cerebrospinal fluid synaptic proteins as useful biomarkers in tyrosine hydroxylase deficiency

Ortez, C.; Duarte, Sofia; Ormazábal, Aída; Serrano, Mercedes; Perez, Ana Paula da Silva; Pons, Roser; Pineda, Mercédes; Yapıcı, Zühal; Fernández-Álvarez, E; Domingo-Jiménez, Rosario; Castro, Pedro de; Artuch, Rafael; García‐Cazorla, Àngels

doi:10.1016/j.ymgme.2014.10.014

Cited by 16 publications

(18 citation statements)

References 25 publications

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“…[ 11 ] In addition, the CSF synaptic proteins dopamine transporter, D2-receptor and vesicular monoamine transporter are regarded as useful biomarkers for THD. [ 12 ]…”

Section: Discussionmentioning

confidence: 99%

Compound heterozygous mutations in the TH gene in a Chinese family with autosomal-recessive dopa-responsive dystonia

et al. 2018

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Rationale:Autosomal-recessive dopa-responsive dystonia (DRD) is a rare clinical disorder presenting as bradykinesia, dystonia, tremor and even severe encephalopathy, and caused by tyrosine hydroxylase deficiency (THD). We report a case of compound heterozygous mutations in the TH gene in a Chinese family with autosomal-recessive DRD herein.Patient concerns:A 16-month-old Chinese boy presented with symptoms of movement disorder and growth retardation in his infant period.Diagnoses:The genetic test revealed compound heterozygous mutations in the TH gene at c.457C>T and c.698G>A, which are pathogenic of DRD.Interventions:The patient was administrated low-dose levodopa.Outcomes:The treatment resulted in the substantial improvement of dystonia. His long-term neurological outcome need follow-up for years.Lessons:Gene mutation analysis is helpful and necessary to diagnose DRD and has important guiding significance for the subsequent treatment.

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“…[ 11 ] In addition, the CSF synaptic proteins dopamine transporter, D2-receptor and vesicular monoamine transporter are regarded as useful biomarkers for THD. [ 12 ]…”

Section: Discussionmentioning

confidence: 99%

Compound heterozygous mutations in the TH gene in a Chinese family with autosomal-recessive dopa-responsive dystonia

et al. 2018

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“…Carriers of the DRD2 A1 allele, then, may have an interesting intrinsic -protective mechanism waiting for amino-acid introduction such as L-phenylalanine and L-tyrosine (rate-limiting substrates in the synthesis of dopamine). Moreover, Ortez et al [244] recently reported that in "tyrosine hydroxylase deficiency" the dopamine transporter (DAT) and vesicular monoamine transporter type 2 were up-regulated leading to a hypodopaminergic trait [244]. Kim et al [245] also showed that locomotor activity responses of these Dopamine-deficient (DA-/-) mice to dopamine D2 receptor agonists were 13-fold greater than the response elicited from wild-type mice [245].…”

Section: Why the Addictive Brain Favors Amino-acid Therapy [Nat™]mentioning

confidence: 99%

Neuronutrient Amino-Acid Therapy Protects Against Reward Deficiency Syndrome: Dopaminergic Key to Homeostasis and Neuroplasticity

Blum

Febo²,

Badgaiyan³

et al. 2016

CPD

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Willuhn et al., observed that habitual cocaine use was correlated with reductions in D2/D3 receptors linked to decreased cue activation in occipital cortex and cerebellum. Dopamine agonist therapy maintains dopamine function and is a relapse prevention tactic focused on psychoactive drug and behavioral addictions. Medication Assisted Treatment (MAT) with emphasis on glutaminergic medications fails in the long-term treatment of Reward Deficiency Syndrome Behaviors (RDS). While the careful use of "dopamine antagonist-therapy" short-term is supported, the research-based concept of "dopamine agonist therapy" in long-term is proposed. Neurogenetics and epigenetics are important in understanding treatment response and clinical outcomes. The neuro-mechanisms involving "dopamine homeostasis" are key to understanding recovery from drug and non-drug addictive behaviors. For example, patients who carry the DRD2 A1 allele (30-40 less D2 receptors) should consider Neuronutriant-Amino-Acid therapy (KB220 variants) a prevention modality. DRD2 A1 allele carriers show amplified striatal function of L-amino acid decarboxylase, prior to dopamine biosynthesis. Another example is the effect of Acute Tyrosine Phenylalanine Depletion (ATPD) on decision-making and reward found carriers with amino-acid deficiency (ATPD). They experienced attenuated reward and reduced decision-making ability as quantified by Iowa Gambling Task (IGT). Future research should be directed at asking the question; Would "dopamine agonist therapy" using KB220 variants reduce methylation and increase acetyl groups to enhance DRD2 expression especially in DRD2 A1 allele carriers and lead to increased dopamine function and a reduction of drug and non-drug seeking behaviors?

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“…Around 70 cases have been reported so far starting not only in infancy but also in adolescence and adulthood. [3][4][5][6][7][8][9][10][11][12] Although different phenotypes have been described, two main forms can be outlined. Type A refers to a progressive hypokinetic-rigid syndrome (HRS) plus dystonia, with onset in infancy or childhood (►Table 1).…”

Section: Clinical Featuresmentioning

confidence: 99%

“…Dopaminergic receptors type 2 increase as L-DOPA doses and HVA concentration gradually raised in a B phenotype patient, whereas the opposite results were found in two patients with A phenotype. 12 Functional studies of TH missense variants have revealed specific kinetic anomalies and activities toward different substrates that may contribute to the development of individualized therapy for THD patients. 14…”

Section: Pathophysiology and Diagnosismentioning

confidence: 99%

Diagnosis of Biogenic Amines Synthesis Defects

et al. 2015

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Defects of biogenic amines synthesis encompass a group of rare genetic disorders that have been described during the last few decades. They include tyrosine hydroxylase deficiency, aromatic L-amino acid decarboxylase deficiency, and pterin defects such as 6-pyruvoyl-tetrahydropterin synthase deficiency, dihydropteridine reductase deficiency, guanosine triphosphate cyclohydrolase-I deficiency, and sepiapterin reductase deficiency. These diseases cause low brain concentrations of catecholamines (dopamine and norepinephrine) and serotonin, which may affect motor, cognitive, and autonomic nervous system. Although most patients have recognizable phenotypes, and share a collection of overlapping symptoms, presentations vary widely and may appear to be nonclassic for the specific disorder. In general, the spectrum of clinical manifestations range from benign forms such as L-3,4-dihydroxyphenylalanine responsive movement disorders to severe encephalopathies that are difficult to treat. These conditions require the specialized analysis of the cerebrospinal fluid because every defect has a very suggestive profile in regard to monoamine and pterin metabolites. However, secondary deficiencies of these metabolites in the cerebrospinal fluid can also be found in a wide variety of neurological disorders. Owing to the still existing challenges of the diagnostic approach, it is important to highlight some of the most relevant clinical and biochemical signatures, as well as to propose practical algorithms that may help clinicians to detect and treat these patients.

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Cerebrospinal fluid synaptic proteins as useful biomarkers in tyrosine hydroxylase deficiency

Cited by 16 publications

References 25 publications

Compound heterozygous mutations in the TH gene in a Chinese family with autosomal-recessive dopa-responsive dystonia

Compound heterozygous mutations in the TH gene in a Chinese family with autosomal-recessive dopa-responsive dystonia

Neuronutrient Amino-Acid Therapy Protects Against Reward Deficiency Syndrome: Dopaminergic Key to Homeostasis and Neuroplasticity

Diagnosis of Biogenic Amines Synthesis Defects

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