Clinical Features in Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency: A Systematic Review

Rizzi, Susanna; Spagnoli, Carlotta; Frattini, Daniele; Pisani, Francesco; Fusco, Carlo

doi:10.1155/2022/2210555

Cited by 18 publications

(38 citation statements)

References 57 publications

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“…Заболевание имеет широкий фенотипический спектр [4,9] и варьирует от тяжелых форм с грубой задержкой моторного развития, ранней мышечной гипотонией, двигательными нарушениями и вегетативной дисфункцией (до 70 % случаев) до умеренных (13 %) и легких форм (5 %) с преимущественно вегетативными симптомами, при которых пациенты способны разговаривать и ходить самостоятельно [3,4,10].…”

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“…Двигательные нарушения являются ведущим клиническим признаком дефицита AADC и включают мышечную гипотонию, чаще осевую (95 %), гипертонус конечностей (44 %), дистонию (53 %), инфантиль-ный паркинсонизм, гипо-и брадикинезию, задержку моторного развития (дети позже начинают держать голову, сидеть, ползать и стоять) [9,12].…”

unclassified

“…Больше половины пациентов имеют трудности с питанием. Один из частых симптомов -нарушения сна, которые имеют тенденцию меняться в зависимости от возраста пациента: для младенцев характерна чрезмерная сонливость, в то время как у детей старше 2 лет наблюдается бессонница [1,3,4,9,11].…”

unclassified

“…Препаратами 1-й линии являются селективные агонисты дофамина, ингибиторы моноаминоксидазы (МАО) типа В и препараты витамина B 6 [4,9]. Пиридоксаль-5-фосфат (pyridoxal 5'-phosphate, PLP) -активная форма пиридоксина (витамина В 6 ), которая является кофактором AADC, что определяет его применение у данной группы пациентов.…”

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“…Пиридоксин является чаще всего используемым препаратом для лечения дефицита AADC (80 % пациентов получали его в разных схемах терапии) благодаря своей низкой цене и доступности [3]. Положительная динамика при этом зарегистрирована у 38 % пациентов [9], тогда как о значительном улучшении состояния сообщается только у 7 % больных [3]. Зарубежные публикации содержат информацию о единичных пациентах, принимающих PLP без очевидного клинического улучшения состояния [4].…”

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Family case of aromatic L-amino acid decarboxylase deficiency

Kondakova

Казакова

Lyalina

et al. 2022

Neuromuscular Diseases

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Aromatic L‑amino acid decarboxylase (AADC) deficiency is rare autosomal recessive neurometabolic disorder. It caused by generalized combined deficiency of serotonin, dopamine, norepinephrine and adrenaline. This disorder is characterized by muscular hypotonia, motor development delay, oculogyric crises and impairment of the autonomic nervous system.Laboratory diagnostic of AADC deficiency in Russian Federation includes determination of the concentration of 3‑O‑methyldophamine in dried blood spots by tandem mass spectrometry and molecular analysis of the DDC gene by Sanger sequencing or next generation sequencing.Therapy of AADC deficiency includes combination of drugs which increase the formation of dopamine, inhibit its reuptake and increase the residual activity of the enzyme. The first‑line drugs are selective dopamine agonists, monoamine oxidase inhibitors of type B and vitamin B6 supplements.We present the case of management and treatment of patients with AADC deficiency. The patient’s condition was improved by using of combination therapy with pyridoxal‑5‑phosphate, pramipexole and selegiline. Significant positive dynamics was achieved on pyridoxal‑5‑phosphate therapy for the first time.

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Family case of aromatic L-amino acid decarboxylase deficiency

Kondakova

Казакова

Lyalina

et al. 2022

Neuromuscular Diseases

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Patient selection considerations for AADC deficiency gene therapy

Roubertie,

Anselm,

Ben‐Zeev

et al. 2024

Annals of the Child Neurology Society

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BackgroundAromatic ʟ‐amino acid decarboxylase (AADC) deficiency is a rare, severe neurological disorder caused by pathogenic variants in the dopa decarboxylase (DDC) gene, resulting in a combined deficiency of monoamine neurotransmitters. Clinically, patients present with a range of dysfunctions that impact motor, autonomic, and cognitive development. The constellation of symptoms of AADC deficiency varies among patients, and clinical presentation falls across a wide spectrum. However, most patients with AADC deficiency experience significant impairments when compared with children with normal development, irrespective of genotype, phenotype, or disease severity. Further, AADC deficiency is associated with increased mortality.MethodsIn response to the recent approval of a disease‐modifying gene therapy for AADC deficiency, this review presents considerations for the selection of patients for treatment.ConclusionSuggested clinical criteria to determine whether a patient is a candidate for gene therapy are: (1) genetically and biochemically confirmed AADC deficiency; (2) lack of achievement of gross motor milestones and/or persistence of clinically significant movement disorders; (3) persistent neurocognitive or systemic symptoms secondary to AADC deficiency despite standard medical therapy; and (4) informed parental/guardian decision and consent to treatment.

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Metabolic characterization of neurogenetic disorders involving glutamatergic neurotransmission

Illescas,

Diaz‐Osorio,

Serradell

et al. 2023

J of Inher Metab Disea

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The study of inborn errors of neurotransmission has been mostly focused on monoamine disorders, GABAergic and glycinergic defects. The study of the glutamatergic synapse using the same approach than classic neurotransmitter disorders is challenging due to the lack of biomarkers in the CSF. A metabolomic approach can provide both insight into their molecular basis and outline novel therapeutic alternatives. We have performed a semi‐targeted metabolomic analysis on CSF samples from 25 patients with neurogenetic disorders with an important expression in the glutamatergic synapse and 5 controls. Samples from patients diagnosed with MCP2, CDKL5‐, GRINpathies and STXBP1‐related encephalopathies were included. We have performed univariate (UVA) and multivariate statistical analysis (MVA), using Wilcoxon rank‐sum test, principal component analysis (PCA), and OPLS‐DA. By using the results of both analyses, we have identified the metabolites that were significantly altered and that were important in clustering the respective groups. On these, we performed pathway‐ and network‐based analyses to define which metabolic pathways were possibly altered in each pathology. We have observed alterations in the tryptophan and branched‐chain amino acid metabolism pathways, which interestingly converge on LAT1 transporter‐dependency to cross the blood–brain barrier (BBB). Analysis of the expression of LAT1 transporter in brain samples from a mouse model of Rett syndrome (MECP2) revealed a decrease in the transporter expression, that was already noticeable at pre‐symptomatic stages. The study of the glutamatergic synapse from this perspective advances the understanding of their pathophysiology, shining light on an understudied feature as is their metabolic signature.

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Clinical Features in Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency: A Systematic Review

Cited by 18 publications

References 57 publications

Family case of aromatic L-amino acid decarboxylase deficiency

Family case of aromatic L-amino acid decarboxylase deficiency

Patient selection considerations for AADC deficiency gene therapy

Metabolic characterization of neurogenetic disorders involving glutamatergic neurotransmission

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