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European Journal of Clinical... Dec 2020To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson's disease. (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson's disease.
METHODS
We performed a systematic literature search identifying randomized controlled trials investigating 4 dopamine agonists (cabergoline, pramipexole, ropinirole, rotigotine) and 3 MAO-B inhibitors (selegiline, rasagiline, safinamide) for Parkinson's disease. We extracted and pooled data from included clinical trials in a joint model allowing both direct and indirect comparison of the seven drugs. We considered dopamine agonists and MAO-B inhibitors given as monotherapy or in combination with levodopa. Selected endpoints were change in the Unified Parkinson's Disease Rating Scale (UPDRS) score, serious adverse events and withdrawals. We estimated the relative effectiveness of each dopamine agonist and MAO-B inhibitor versus comparator drug.
RESULTS
Altogether, 79 publications were included in the analysis. We found all the investigated drugs to be effective compared with placebo when given as monotherapy except safinamide. When considering combination treatment, the estimated relative effects of selegiline, pramipexole, ropinirole, rotigotine, cabergoline, rasagiline and safinamide were 2.316 (1.819, 2.951), 2.091 (1.889, 2.317), 2.037 (1.804, 2.294), 1.912 (1.716, 2.129), 1.664 (1.113, 2.418), 1.584 (1.379, 1.820) and 1.179 (1.031, 1.352), respectively, compared with joint placebo and levodopa treatment.
CONCLUSIONS
Dopamine agonists were found to be effective as treatment for Parkinson's disease, both when given as monotherapy and in combination with levodopa. Selegiline and rasagiline were also found to be effective for treating Parkinson's disease, and selegiline was the best option in combination with levodopa among all the drugs investigated.
Topics: Dopamine Agonists; Drug Therapy, Combination; Humans; Indans; Levodopa; Monoamine Oxidase Inhibitors; Parkinson Disease; Randomized Controlled Trials as Topic; Selegiline; Treatment Outcome
PubMed: 32710141
DOI: 10.1007/s00228-020-02961-6 -
The Cochrane Database of Systematic... Aug 2022Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is... (Review)
Review
BACKGROUND
Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is characterised by social communication difficulties and repetitive and restricted behaviours and routines that can have a negative impact on a child's quality of life, achievement at school, and social interactions with others. It has been hypothesised that memantine, which is traditionally used to treat dementia, may be effective in reducing the core symptoms of autism as well as some co-occurring symptoms such as hyperactivity and language difficulties. If memantine is being used to treat the core symptoms of autism, it is important to review the evidence of its effectiveness.
OBJECTIVES
To assess the effects of memantine on the core symptoms of autism, including, but not limited to, social communication and stereotypical behaviours.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, nine other databases and three trials registers up to February 2022. We also checked reference lists of key studies and checked with experts in the field for any additional papers. We searched for retractions of the included studies in MEDLINE, Embase, and the Retraction Watch Database. No retractions or corrections were found.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of any dose of memantine compared with placebo in autistic people. We also included RCTs in which only one group received memantine, but both groups received the same additional therapy (e.g. a behaviour intervention).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were core autism symptoms and adverse effects. Secondary outcomes were language, intelligence, memory, adaptive behaviour, hyperactivity, and irritability. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included three RCTs (two double-blind and one single-blind) with 204 participants that examined the short-term effect (immediately postintervention) of memantine in autistic people. Two studies took place in the USA and the other in Iran. All three studies focused on children and adolescents, with a mean age of 9.40 (standard deviation (SD) 2.26) years. Most participants were male (range across studies 73% to 87%). The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders (4th edition; 4th edition, text revision; or 5th edition). To confirm the diagnosis, one study used the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R); one used ADOS, ADI-R or the Autism Diagnostic Interview Screener; and one used the Gilliam Autism Rating Scale. Dosage of memantine was based on the child's weight and ranged from 3 mg to 15 mg per day. Comparisons Two studies examined memantine compared with placebo; in the other study, both groups had a behavioural intervention while only one group was given memantine. Risk of bias All studies were rated at high risk of bias overall, as they were at high or unclear risk of bias across all but four domains in one study, and all but two domains in the other two studies. One study was funded by Forest Laboratories, LLC, (Jersey City, New Jersey), Allergan. The study sponsor was involved in the study design, data collection (via contracted clinical investigator sites), analysis and interpretation of data, and the decision to present these results. The other two studies reported no financial support or sponsorship; though in one of the two, the study medication was an in-kind contribution from Forest Pharmaceuticals. Primary outcomes There was no clear evidence of a difference between memantine and placebo with respect to severity of core symptoms of autism, although we are very uncertain about the evidence. The standardised mean difference in autism symptoms score in the intervention group versus the control group was -0.74 standard deviations (95% confidence interval (CI) -2.07 to 0.58; 2 studies, 181 participants; very low-certainty evidence; medium effect size); lower scores indicate less severe autistic symptoms. Two studies (144 participants) recorded adverse effects that the authors deemed related to the study and found there may be no difference between memantine and placebo (odds ratio (OR) 0.64, 95% CI 0.17 to 2.39; low-certainty evidence). Secondary outcomes There may be no difference between memantine and placebo on language (2 studies, 144 participants; low-certainty evidence); memory or adaptive behaviour (1 study, 23 participants; both low-certainty evidence); or hyperactivity or irritability (1 study, 121 participants; both low-certainty evidence).
AUTHORS' CONCLUSIONS
It is unclear whether memantine is an effective treatment for autistic children. None of the three included trials reported on the effectiveness of memantine in adults. Further studies using rigorous designs, larger samples, longer follow-up and clinically meaningful outcome measures that are important to autistic people and their families will strengthen our knowledge of the effects of memantine in autism.
Topics: Adolescent; Adult; Autism Spectrum Disorder; Child; Female; Humans; Male; Memantine; Odds Ratio; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36006807
DOI: 10.1002/14651858.CD013845.pub2 -
Current Problems in Cardiology Feb 2023Heart failure (HF) is one of the leading causes of maternal mortality and morbidity in the United States. Peripartum cardiomyopathy (PPCM) constitutes up to 70% of all... (Meta-Analysis)
Meta-Analysis Review
Heart failure (HF) is one of the leading causes of maternal mortality and morbidity in the United States. Peripartum cardiomyopathy (PPCM) constitutes up to 70% of all HF in pregnancy. Cardiac angiogenic imbalance caused by cleaved 16kDa prolactin has been hypothesized to contribute to the development of PPCM, fueling investigation of prolactin inhibitors for the management of PPCM. We conducted a systematic review and meta-analysis to assess the impact of prolactin inhibition on left ventricular (LV) function and mortality in patients with PPCM. We included English language articles from PubMed and EMBASE published upto March 2022. We pooled the mean difference (MD) for left ventricular ejection fraction (LVEF) at follow-up, odds ratio (OR) for LV recovery and risk ratio (RR) for all-cause mortality using random-effects meta-analysis. Among 548 studies screened, 10 studies (3 randomized control trials (RCTs), 2 retrospective and 5 prospective cohorts) were included in the systematic review. Patients in the Bromocriptine + standard guideline directed medical therapy (GDMT) group had higher LVEF% (pMD 12.56 (95% CI 5.84-19.28, I2=0%) from two cohorts and pMD 14.25 (95% CI 0.61-27.89, I2=88%) from two RCTs) at follow-up compared to standard GDMT alone group. Bromocriptine group also had higher odds of LV recovery (pOR 3.55 (95% CI 1.39-9.1, I2=62)). We did not find any difference in all-cause mortality between the groups. Our analysis demonstrates that the addition of Bromocriptine to standard GDMT was associated with a significant improvement in LVEF% and greater odds of LV recovery, without significant reduction in all-cause mortality.
Topics: Pregnancy; Female; Humans; Bromocriptine; Prolactin; Peripartum Period; Cardiomyopathies; Ventricular Function, Left; Heart Failure; Stroke Volume; Pregnancy Complications, Cardiovascular
PubMed: 36261102
DOI: 10.1016/j.cpcardiol.2022.101461 -
The Cochrane Database of Systematic... Nov 2014Influenza is an acute respiratory illness caused by influenza A and B viruses. Complications may occur, especially among children and the elderly. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Influenza is an acute respiratory illness caused by influenza A and B viruses. Complications may occur, especially among children and the elderly.
OBJECTIVES
To assess the effectiveness and safety of amantadine and rimantadine in preventing, treating and shortening the duration of influenza A in children and the elderly.
SEARCH METHODS
We searched CENTRAL (2014, Issue 9), MEDLINE (1966 to September week 4, 2014) and EMBASE (1980 to October 2014).
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-RCTs comparing amantadine and/or rimantadine with no intervention, placebo, other antivirals or different doses or schedules of amantadine or rimantadine in children and the elderly with influenza A.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the search results. We extracted and analysed data using the standard Cochrane methodology.
MAIN RESULTS
We identified 12 studies (2494 participants: 1586 children and 908 elderly) comparing amantadine and rimantadine with placebo, paracetamol (one trial: 69 children) or zanamivir (two trials: 545 elderly) to treat influenza A.Amantadine was effective in preventing influenza A in children (773 participants, risk ratio (RR) 0.11; 95% confidence interval (CI) 0.04 to 0.30). The assumed risk of influenza A in the control group was 10 per 100. The corresponding risk in the rimantadine group was one per 100 (95% CI 0 to 3). Nevertheless, the quality of the evidence was low and the safety of the drug was not well established.For treatment, rimantadine was beneficial in abating fever on day three of treatment in children: one selected study with low risk of bias, moderate evidence quality and 69 participants (RR 0.36; 95% CI 0.14 to 0.91). The assumed risk was 38 per 100. The corresponding risk in the rimantadine group was 14 per 100 (95% CI 5 to 34).Rimantadine did not show any prophylactic effect in the elderly. The quality of evidence was very low: 103 participants (RR 0.45; 95% CI 0.14 to 1.41). The assumed risk was 17 per 100. The corresponding risk in the rimantadine group was 7 per 100 (95% CI 2 to 23).There was no evidence of adverse effects caused by treatment with amantadine or rimantadine.We found no studies assessing amantadine in the elderly.
AUTHORS' CONCLUSIONS
The quality of the evidence combined with a lack of knowledge about the safety of amantadine and the limited benefits of rimantadine, do not indicate that amantadine and rimantadine compared to control (placebo or paracetamol) could be useful in preventing, treating and shortening the duration of influenza A in children and the elderly.
Topics: Adolescent; Aged; Amantadine; Antiviral Agents; Child; Humans; Influenza A Virus, H1N1 Subtype; Influenza A virus; Influenza, Human; Randomized Controlled Trials as Topic; Rimantadine; Sex Factors; Young Adult
PubMed: 25415374
DOI: 10.1002/14651858.CD002745.pub4 -
Medicine Apr 2024Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and daily living ability. Currently, there are not many drugs that can be selected to treat mild to moderate AD, and the value of drugs remains controversial.
OBJECTIVE
The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) in the treatment of patients with AD. Additionally, molecular docking analysis will be used to investigate the binding affinities of donepezil, galantamine, rivastigmine, and memantine with key receptor proteins associated with AD, including beta-amyloid (Abeta), microtubule-associated protein (MAP), apolipoprotein E4 (APOE4), and Mitofusin-2 (MFN2), to further validate the results of the meta-analysis.
METHODS
We obtained clinical trials characterized by randomization, placebo control, and double-blinded methodologies concerning ChEIs, memantine, and GV-971. Statistical analysis was performed using Review Manager Version 5.4 software. Molecular docking was also conducted to evaluate the results.
RESULTS
All drugs improved the cognitive function, with the effect value ranging from -1.23 (95% CI -2.17 to -0.30) for 20 mg memantine to -3.29 (95% CI -4.14 to -2.45) for 32 mg galantamine. Although 32 mg galanthamine and GV-971 did not improve the clinicians' Global Impression of Change scale, other drugs showed significant results compared with placebo. On NPI, only 10 mg of donepezil and 24 mg of galantamine had improvement effects. On ADCS/ADL, only 20 mg memantine and 900 mg GV-971 had no significant difference from the placebo. Donepezil 5 mg and GV-971 900 mg did not increase the drug withdrawal rates due to various reasons or adverse reactions when compared to the placebo. Donepezil demonstrated superior binding to the protein and exhibited greater efficacy compared to other drugs.
CONCLUSION
ChEIs, memantine, and GV-971 all can slow the progression of AD but have different effects on respective assessments. Donepezil and GV-971 were relatively well tolerated.
Topics: Humans; Alzheimer Disease; Donepezil; Galantamine; Memantine; Molecular Docking Simulation; Cholinesterase Inhibitors; Rivastigmine
PubMed: 38640313
DOI: 10.1097/MD.0000000000037799 -
Journal of Geriatric Psychiatry and... Sep 2022Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue.
METHODS
We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available.
RESULTS
Twenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81-6.46]), (OR 1.39 [95% CI:0.97-1.98]).
CONCLUSIONS
Most studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH.
Topics: Antiparkinson Agents; Dopamine Agonists; Humans; Hypotension, Orthostatic; Levodopa; Monoamine Oxidase; Parkinson Disease
PubMed: 34964392
DOI: 10.1177/08919887211060017 -
Movement Disorders : Official Journal... Jul 2021This Movement Disorder Society Genetic mutation database Systematic Review focuses on monogenic atypical parkinsonism with mutations in the ATP13A2, DCTN1, DNAJC6,...
This Movement Disorder Society Genetic mutation database Systematic Review focuses on monogenic atypical parkinsonism with mutations in the ATP13A2, DCTN1, DNAJC6, FBXO7, SYNJ1, and VPS13C genes. We screened 673 citations and extracted genotypic and phenotypic data for 140 patients (73 families) from 77 publications. In an exploratory fashion, we applied an automated classification procedure via an ensemble of bootstrap-aggregated ("bagged") decision trees to distinguish these 6 forms of monogenic atypical parkinsonism and found a high accuracy of 86.5% (95%CI, 86.3%-86.7%) based on the following 10 clinical variables: age at onset, spasticity and pyramidal signs, hypoventilation, decreased body weight, minimyoclonus, vertical gaze palsy, autonomic symptoms, other nonmotor symptoms, levodopa response quantification, and cognitive decline. Comparing monogenic atypical with monogenic typical parkinsonism using 2063 data sets from Movement Disorder Society Genetic mutation database on patients with SNCA, LRRK2, VPS35, Parkin, PINK1, and DJ-1 mutations, the age at onset was earlier in monogenic atypical parkinsonism (24 vs 40 years; P = 1.2647 × 10) and levodopa response less favorable than in patients with monogenic typical presentations (49% vs 93%). In addition, we compared monogenic to nonmonogenic atypical parkinsonism using data from 362 patients with progressive supranuclear gaze palsy, corticobasal degeneration, multiple system atrophy, or frontotemporal lobar degeneration. Although these conditions share many clinical features with the monogenic atypical forms, they can typically be distinguished based on their later median age at onset (64 years; IQR, 57-70 years). In conclusion, age at onset, presence of specific signs, and degree of levodopa response inform differential diagnostic considerations and genetic testing indications in atypical forms of parkinsonism. © 2021 International Parkinson and Movement Disorder Society.
Topics: Genotype; Humans; Levodopa; Parkinson Disease; Parkinsonian Disorders; Phenotype
PubMed: 34396589
DOI: 10.1002/mds.28517 -
Frontiers in Endocrinology 2023As a popular antidiabetic drug, teneligliptin has been used for over 10 years, but its efficacy and safety have rarely been systematically evaluated. Therefore, a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
As a popular antidiabetic drug, teneligliptin has been used for over 10 years, but its efficacy and safety have rarely been systematically evaluated. Therefore, a Bayesian network meta-analysis was conducted to evaluate the efficacy and safety of teneligliptin in patients with type 2 diabetes mellitus (T2DM).
METHODS
We systematically searched PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Randomized controlled trials (RCTs) comparing teneligliptin with placebo or active comparators in T2DM patients for at least 12 weeks were included in the study. Data analysis was performed using R 4.2.3 and Stata 17.0 software. Each outcome was presented as a mean difference (MD) or an odds ratio (OR) along with 95% confidence interval (CI) and the surface under the cumulative ranking curve value (SUCRA).
RESULTS
A total of 18 RCTs with 3,290 participants with T2DM were included in this study. Generally, compared to placebo, sitagliptin, vildagliptin, metformin, and bromocriptine, 20 mg of teneligliptin showed better efficacy in reducing HbA1c (MD [95% CI], -0.78 [-0.86 to -0.70], -0.08 [-0.36 to 0.19], -0.04 [-0.72 to 0.60], -0.12 [-0.65 to 0.42], and -0.50 [-0.74 to -0.26], respectively) and fasting plasma glucose (FPG) (MD [95% CI], -18.02 [-20.64 to -15.13], 1.17 [-9.39 to 11.70], -8.06 [-30.95 to 14.35], -2.75 [-18.89 to 13.01], and -34.23 [-45.93 to -22.96], respectively), and 40 mg of teneligliptin also showed better efficacy in reducing HbA1c (MD [95% CI], -0.84 [-1.03 to -0.65], -0.15 [-0.49 to 0.19], -0.10 [-0.81 to 0.57], -0.18 [-0.76 to 0.39], and -0.56 [-0.88 to -0.26], respectively) and FPG (MD [95% CI], -20.40 [-26.07 to -14.57], -1.20 [-13.21 to 10.38], -10.43 [-34.16 to 12.65], -5.13 [-22.21 to 11.66], and -36.61 [-49.33 to -24.01], respectively). Compared to placebo, 20 mg of teneligliptin showed no significant difference in incidences of hypoglycemia and gastrointestinal adverse events (OR [95% CI], 1.30 [0.70 to 2.19] and 1.48 [0.78 to 2.98], respectively), and 40 mg of teneligliptin showed no significant difference in incidence of hypoglycemia (OR [95% CI], 2.63 [0.46 to 8.10]). Generally, antidiabetic effect and hypoglycemia risk of teneligliptin gradually increased as its dose increased from 5 mg to 40 mg. Compared to 20 mg of teneligliptin, 40 mg of teneligliptin showed superior efficacy and no-inferior safety, which was considered as the best option in reducing HbA1c, FPG, and 2h PPG and increasing proportion of the patients achieving HbA1c < 7% (SUCRA, 85.51%, 84.24%, 79.06%, and 85.81%, respectively) among all the included interventions.
CONCLUSION
Compared to sitagliptin, vildagliptin, metformin, bromocriptine, and placebo, teneligliptin displayed favorable efficacy and acceptable safety in treating T2DM. Twenty milligrams or 40 mg per day was the optimal dosage regimen of teneligliptin. The results of this study will provide important evidence-based basis for rational use of teneligliptin and clinical decision-making of T2DM medication.
Topics: Humans; Bromocriptine; Glycated Hemoglobin; Network Meta-Analysis; Vildagliptin; Diabetes Mellitus, Type 2; Metformin; Sitagliptin Phosphate; Hypoglycemic Agents; Hypoglycemia
PubMed: 38189048
DOI: 10.3389/fendo.2023.1282584 -
Medicina (Kaunas, Lithuania) Feb 2023: So far, there is little evidence of the ambient effect on motor and non-motor symptoms of Parkinson's Disease (PD). This systematic review aimed to determine the... (Review)
Review
: So far, there is little evidence of the ambient effect on motor and non-motor symptoms of Parkinson's Disease (PD). This systematic review aimed to determine the association between ambiental factors and the progression of PD. A systematic literature search of PubMed, Cochrane, Embase, and Web of Science was conducted up to 21 December 2021 according the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. : Eight articles were used in the analyses. Long-term exposure to fine particles (particulate matter ≤ 2.5 μm; PM) was positively associated with disease aggravation in two studies. Short-term PM exposure was positively associated with disease aggravation in three studies. Significant associations were found between PD aggravation and NO, SO, CO, nitrate and organic matter (OM) concentrations in two studies. Associations were more pronounced, without reaching statistical significance however, in women, patients over 65 years old and cold temperatures. A 1% increase in temperature was associated with a significant 0.18% increase in Levodopa Equivalent Dose (LED). Ultraviolet light and humidity were not significantly associated with an increase in LED. There was no difference in hallucination severity with changing seasons. There was no evidence for seasonal fluctuation in Unified Parkinson's Disease Rating Scale (UPDRS) scores. : There is a link between air pollutants and temperature for PD progression, but this has yet to be proven. More longitudinal studies are warranted to confirm these findings.
Topics: Humans; Female; Aged; Parkinson Disease; Levodopa; Air Pollutants; Particulate Matter; Disease Progression
PubMed: 36837495
DOI: 10.3390/medicina59020294 -
Behavioural Neurology 2022Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare congenital autosomal recessive metabolic disorder caused by pathogenic homozygous or compound... (Review)
Review
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare congenital autosomal recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the dopa decarboxylase (DDC) gene. Adeno-associated viral vector-mediated gene transfer of the human AADC gene into the putamina has become available. This systematic review on PubMed, Scopus databases, and other sources is aimed at describing the AADC whole phenotypic spectrum in order to facilitate its early diagnosis. Literature reviews, original articles, retrospective and comparative studies, large case series, case reports, and short communications were considered. A database was set up using Microsoft Excel to collect clinical, molecular, biochemical, and therapeutic data. By analysing 261 patients from 41 papers with molecular and/or biochemical diagnosis of AADC deficiency for which individuality could be determined with certainty, we found symptom onset to occur in the first 6 months of life in 93% of cases. Hypotonia and developmental delay are cardinal signs, reported as present in 73.9% and 72% of cases, respectively. Oculogyric crises were seen in 67% of patients while hypokinesia in 42% and ptosis in 26%. Dysautonomic features have been revealed in 53% and gastrointestinal symptoms in 19% of cases. With 37% and 30% of patients reported being affected by sleep and behavioural disorders, it seems to be commoner than previously acknowledged. Although reporting bias cannot be excluded, there is still a need for comprehensive clinical descriptions of symptoms at onset and during follow-up. In fact, our review suggests that most of the neurological and extraneurological symptoms and signs reported, although quite frequent in this condition, are not pathognomonic, and therefore, ADCC deficiency can remain an underdiscovered disorder.
Topics: Humans; Dopa Decarboxylase; Retrospective Studies; Amino Acid Metabolism, Inborn Errors; Amino Acids
PubMed: 36268467
DOI: 10.1155/2022/2210555