She became pale and sweaty with hypothermia (33.5°C), bradycardia (45 bpm), and acidosis and presented a generalized seizure. [ncbi.nlm.nih.gov]

Symptoms can include: Hypotonia (floppiness) Developmental delay Oculogyric crises[2] Difficulty with initiating and controlling movements Dystonia and dyskinesia Gastointestinal dysmotility which can present at as vomiting, gastro-oesophageal reflux, [en.wikipedia.org]

• Developmental Delay

  Aromatic L-amino acid decarboxylase deficiency Specialty Neurology Symptoms Dystonia, oculogyric crises, developmental delay, parkinsonism, dysautonomia Usual onset Infancy Causes Autosomal recessive DDC mutation Diagnostic method Lumbar puncture for [en.wikipedia.org]

  Our male patient presented with developmental delay, extreme hypotonia, oculogyric crises, and irritability. [ncbi.nlm.nih.gov]

• Movement Disorder

  The child showed the characteristic clinical picture of an extrapyramidal movement disorder, oculogyric crises and vegetative symptoms seen in the three patients described previously. [ncbi.nlm.nih.gov]

  In addition, he established the Rush Movement Disorder Surgery Program and serves as its Medical Director. His clinical research interests include the development of new medical and surgical therapies for patients with advanced movement disorders. [books.google.ro]

  94 Paroxysmal Dyskinesias E-1637 95 Movement Disorders of Infancy E-1646 96 DrugInduced Movement Disorders in Children E-1651 97 Cerebral Palsy E-1660 98 Tics and Tourette Syndrome E-1673 99 Genetic and Metabolic Disorders of the White Matter E-1690 100 [books.google.de]

• Hypothermia

  She became pale and sweaty with hypothermia (33.5°C), bradycardia (45 bpm), and acidosis and presented a generalized seizure. [ncbi.nlm.nih.gov]

  Clinically this results in the development of a progressive neurometabolic disorder characterized by severe hypotonia, dystonic and choreoathetoid movements, oculogyric crises, and hypothermia from infancy. [thieme-connect.com]

  It causes developmental and psychomotor delay, poor feeding, lethargy, ptosis, intermittent hypothermia, gastrointestinal disturbances. The onset is early in infancy and inheritance is autosomal recessive. [uniprot.org]

• Weakness

  Affected infants may have severe developmental delay, weak muscle tone (hypotonia), muscle stiffness, difficulty moving, and involuntary writhing movements of the limbs (athetosis). [ghr.nlm.nih.gov]

  Symptoms of AADC deficiency include severe developmental delay, weak muscle tone (hypotonia), muscle stiffness, difficulty moving, and involuntary writhing movements of the limbs (athetosis). [welcomehomeangel.com]

  Symptoms may include severe delay in reaching milestones such as walking and talking (developmental delay ), weak muscle tone (hypotonia ), muscle stiffness, difficulty moving, and involuntary writhing movements of the limbs (athetosis). [rarediseases.info.nih.gov]

  […] promiscuity Low CYP Inhibitory Promiscuity 0.8947 Ames test Non AMES toxic 0.9133 Carcinogenicity Non-carcinogens 0.9519 Biodegradation Not ready biodegradable 0.7897 Rat acute toxicity 2.9260 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak [drugbank.ca]

• Feeding Difficulties

  The index patient and her brother both had poor sucking power and feeding difficulty at birth and episodes of oculogyric crises, truncal hypotonia, limb hypertonia, sleep disturbances, irritability, and motor delay. [ncbi.nlm.nih.gov]

  difficulties Hypersalivation Tongue thrusting Gastrointestinal symptoms (dysmotility and absorption, gastroesophageal reflux, constipation and diarrhea) Nasal congestion Developmental delay Hypersensitivity to sensory stimuli Increased startle Head drops [pndassoc.org]

  This condition may also cause infants to lack energy, feed poorly, startle easily, and have sleep disturbances.[1] Many people with AADC deficiency experience episodes called oculogyric crises (also called "spells" or "attacks"), which are characterized [rarediseases.info.nih.gov]

  The presentation of symptoms is variable and there are variable degrees of severity Neonatal Period Feeding difficulties Autonomic dysfunction Hypotonia Motor symptoms Axial hypotonia (decreased tone or floppy - trunk, head and limbs) Limb hypertonia [aadcresearch.org]

• Nasal Congestion

  All patients presented distinct extraneurological symptoms, such as hypersalivation, hyperhidrosis, nasal congestion, sleep disturbances and hypoglycaemia. [ncbi.nlm.nih.gov]

  congestion Some people may develop cerebral folate deficiency, because O-methylation of the excessive amounts of L-Dopa can deplete methyl donors such as S-adenosyl methionine and levomefolic acid. [en.wikipedia.org]

  Resulting signs and symptoms can include droopy eyelids (ptosis), constriction of the pupils of the eyes (miosis), inappropriate or impaired sweating, nasal congestion, drooling, reduced ability to control body temperature, low blood pressure (hypotension [ghr.nlm.nih.gov]

• Stridor

  Usually they begin in the afternoon and are characterized by increased irritability, crying, abnormal eye movements, stiffness withabnormal posturing and stridor (rattled breathing). [pndassoc.org]

• Diarrhea

  A 5-year-old girl with a medical history of chronic diarrhea presented three episodes of severe hypoglycemia (20 mg/dL) between ages 3 and 5 years. [ncbi.nlm.nih.gov]

  […] or disrupted) Absence of speech Irritability and crying Stridor (rattled breathing) Swallowing and feeding difficulties Hypersalivation Tongue thrusting Gastrointestinal symptoms (dysmotility and absorption, gastroesophageal reflux, constipation and diarrhea [pndassoc.org]

  Diarrhea in streptozocin-treated rats. Loss of adrenergic regulation of intestinal fluid and electrolyte transport. J Clin Invest 1985;75:1666-70. CrossRef 8. Swoboda KJ, Saul JP, McKenna CE, Speller NB, Hyland K. [hkmj.org]

  […] is not available through HPO Abnormality of the face Abnormal face Facial abnormality [ more ] 0000271 Autosomal recessive inheritance 0000007 Babinski sign 0003487 Choreoathetosis 0001266 Constipation 0002019 Decreased CSF homovanillic acid 0003785 Diarrhea [rarediseases.info.nih.gov]

• Constipation

  [medical citation needed] Individuals may also need to take a range of other medications to control dyskinesia, constipation and other symptoms.[1] In July 2021, results of a small gene therapy phase I study reported observation of dopamine restoration [en.wikipedia.org]

  […] disturbance (excessive or disrupted) Absence of speech Irritability and crying Stridor (rattled breathing) Swallowing and feeding difficulties Hypersalivation Tongue thrusting Gastrointestinal symptoms (dysmotility and absorption, gastroesophageal reflux, constipation [pndassoc.org]

  Learn More: HPO ID Percent of people who have these symptoms is not available through HPO Abnormality of the face Abnormal face Facial abnormality [ more ] 0000271 Autosomal recessive inheritance 0000007 Babinski sign 0003487 Choreoathetosis 0001266 Constipation [rarediseases.info.nih.gov]

  Constipation is also a common finding. As affected infants age, they may experience behavioral problems including attention deficiency hyperactivity disorder, impulsivity, anxiety, depression and obsessive-compulsive disorder. [rarediseases.org]

  […] neurologic symptoms after sleep Autonomic dysfunction Diaphoresis Temperature instability Nasal congestion Ptosis/pupillary changes (droopy eyelids) Hypotension/bradyarrhythmia RAD/GI dysmotility (Gastrointestinal symptoms including gastroesophageal reflux, constipation [aadcresearch.org]

• Hypotension

  This report presents the case of an adult male with aromatic L-amino acid decarboxylase deficiency who developed serious cardiac rhythm disturbances during treatment with intravenous dopamine and norepinephrine for severe hypotension. [ncbi.nlm.nih.gov]

  Congenital eyelid ptosis, decreased glomerular filtration, and orthostatic hypotension: Answers T Wassenberg, M Willemsen, H Dijkman, J Deinum, L Monnens Pediatric Nephrology 32 (7), 1171-1174, 2017 2017 the explanation for urinary dopamine excretion [scholar.google.it]

  When he was 11 years old, there was an episode of protracted hypotension with bradycardia (for 5 hours), which followed sedation (with diazepam 0.1 mg/kg) for an oesophagogastroduodenoscopy. [hkmj.org]

  Resulting signs and symptoms can include droopy eyelids (ptosis), constriction of the pupils of the eyes (miosis), inappropriate or impaired sweating, nasal congestion, drooling, reduced ability to control body temperature, low blood pressure (hypotension [ghr.nlm.nih.gov]

  Orthostatic hypotension and Holmes-Adie syndrome. Usefulness of the Valsalva ratio in the evaluation of baroreceptor dysfunction. J Hum Hypertens. 2002 Sep. 16(9):661-2. [Medline]. [emedicine.medscape.com]

• Orthostatic Hypotension

  Congenital eyelid ptosis, decreased glomerular filtration, and orthostatic hypotension: Answers T Wassenberg, M Willemsen, H Dijkman, J Deinum, L Monnens Pediatric Nephrology 32 (7), 1171-1174, 2017 2017 the explanation for urinary dopamine excretion [scholar.google.it]

  Postural orthostatic tachycardia syndrome: the Mayo clinic experience. Mayo Clin Proc. 2007 Mar. 82(3):308-13. [Medline]. Freeman R. Current pharmacologic treatment for orthostatic hypotension. Clin Auton Res. 2008 Mar. 18 Suppl 1:14-8. [Medline]. [emedicine.medscape.com]

• Hypersalivation

  All patients presented distinct extraneurological symptoms, such as hypersalivation, hyperhidrosis, nasal congestion, sleep disturbances and hypoglycaemia. [ncbi.nlm.nih.gov]

  Clinical Presentation: symptoms may include temperature instability, ptosis of the eyelids, hypersalivation, distal chorea, swallowing difficulties, drowsiness, irritability, truncal hypotonia, oculogyric crises, pinpoint pupils. [ndrf.org]

  […] temperature regulation, heart rate fluctuations) Excessive sweating Dysphoria and emotional lability Sleep disturbance (excessive or disrupted) Absence of speech Irritability and crying Stridor (rattled breathing) Swallowing and feeding difficulties Hypersalivation [pndassoc.org]

  Selegiline has been reported to improve oculogyric crises, muscle tone and strength, gastro-intestinal function, hypersalivation and sleep patterns, but according to some reports such effects were transient. 9 Pyridoxine (usual dosage of 100-400 mg/day [hkmj.org]

• Abnormal Eye Movement

  Patients with AADC suffer from severe movement disorders, abnormal eye movements, autonomic symptoms and neurological impairment. What symptoms are associated with AADC? The most common symptom of AADC is referred to as a “Spell” or “Attack”. [pndassoc.org]

  The patient was treated with carbamazepine, but there was minimal improvement of his abnormal eye movements. [hkmj.org]

  Abnormalities of eye movement may range from brief upward eye-rolling movements to oculogyric crisis, a condition characterized by eyes that roll upward for a sustained period of time. [rarediseases.org]

• Miosis

  Resulting signs and symptoms can include droopy eyelids (ptosis), constriction of the pupils of the eyes (miosis), inappropriate or impaired sweating, nasal congestion, drooling, reduced ability to control body temperature, low blood pressure (hypotension [ghr.nlm.nih.gov]

  Onset in first year of life Onset in infancy [ more ] 0003593 Intermittent hypothermia Intermittent abnormally low body temperature 0005964 Irritability Irritable 0000737 Limb dystonia 0002451 Limb hypertonia Increased muscle tone of arm or leg 0002509 Miosis [rarediseases.info.nih.gov]

  Autonomic symptoms have included ptosis, miosis, paroxysmal sweating, nasal congestion, temperature instability, hypotension, and gastroesophageal reflux. [jn.nutrition.org]

• Muscle Spasm

  People with AADC deficiency may also experience episodes called oculogyric crises that involve abnormal rotation of the eyeballs; extreme irritability and agitation; and pain, muscle spasms, and uncontrolled movements, especially of the head and neck. [ghr.nlm.nih.gov]

  Affected infants may also develop spasms of the neck muscles that result in involuntary rotation and tilting of the head and twisting of the neck (torticollis). [rarediseases.org]

  spasms, and uncontrolled movements of the head and neck.[1][2]. [rarediseases.info.nih.gov]

• Small Hand

  In addition, we observed that all patients (100.0%) had small hands and feet. [ncbi.nlm.nih.gov]

• Myopathy

  E-2529 149 Metabolic Myopathies E-2547 150 Inflammatory Myopathies E-2595 151 Channelopathies E-2605 152 Management of Children with Neuromuscular Disorders E-2626 153 Endocrine Disorders of the Hypothalamus and Pituitary in Childhood and Adolescence [books.google.de]

• Sweating

  Increased sweating Profuse sweating Sweating Sweating profusely Sweating, increased [ more ] 0000975 Hyperreflexia Increased reflexes 0001347 Hypotension Low blood pressure 0002615 Infantile onset Onset in first year of life Onset in infancy [ more ] [rarediseases.info.nih.gov]

  Of 12 patients enrolled, clinical presentations included global developmental delay with generalized hypotonia in 12 (100%), dystonia in 12 (100%), oculogyric crisis in 12 (100%), and excessive sweating in 8 (67%). [ncbi.nlm.nih.gov]

  […] controlling movements Dystonia and dyskinesia Gastointestinal dysmotility which can present at as vomiting, gastro-oesophageal reflux, diarrhoea and/or constipation Autonomic symptoms including difficulties controlling temperature and blood sugar, excessive sweating [en.wikipedia.org]

  Resulting signs and symptoms can include droopy eyelids (ptosis), constriction of the pupils of the eyes (miosis), inappropriate or impaired sweating, nasal congestion, drooling, reduced ability to control body temperature, low blood pressure (hypotension [ghr.nlm.nih.gov]

  […] gaze, eyes darting side to side) Ptosis (droopy eyelids) Dystonia Paucity of spontaneous movements Limb tremor with attempted voluntary movement Autonomic dysfunction (blood pressure and body temperature regulation, heart rate fluctuations) Excessive sweating [pndassoc.org]

• Hyperhidrosis

  All patients presented distinct extraneurological symptoms, such as hypersalivation, hyperhidrosis, nasal congestion, sleep disturbances and hypoglycaemia. [ncbi.nlm.nih.gov]

  […] acid 0003785 Diarrhea Watery stool 0002014 Emotional lability Emotional instability 0000712 Feeding difficulties in infancy 0008872 Gastroesophageal reflux Acid reflux Acid reflux disease Heartburn [ more ] 0002020 Global developmental delay 0001263 Hyperhidrosis [rarediseases.info.nih.gov]

  Botulinum toxin for hyperhidrosis: a review. Am J Clin Dermatol. 2009. 10(2):87-102. [Medline]. Monteiro E, Perdigoto R, Furtado AL. Liver transplantation for familial amyloid polyneuropathy. Hepatogastroenterology. 1998 Sep-Oct. 45(23):1375-80. [emedicine.medscape.com]

• Increased Sweating

  Increased sweating Profuse sweating Sweating Sweating profusely Sweating, increased [ more ] 0000975 Hyperreflexia Increased reflexes 0001347 Hypotension Low blood pressure 0002615 Infantile onset Onset in first year of life Onset in infancy [ more ] [rarediseases.info.nih.gov]

  In children with AADC deficiency, these medications have been reported to help reduce the increased sweating and possibly ameliorate the limb dystonia. It has been reported that it may help in the smoothing out of motor fluctuations. [aadcresearch.org]

• Behavior Disorder

  Glutamic acid can be used in correcting personality disorders and treating childhood behavioral disorders. It also takes places in treating epilepsy, mental retardation, muscular dystrophy, ulcers, and hypoglycemic coma. [en.wikibooks.org]

• Dysphoric Mood

  The Symptoms associated with AADC deficiency AADC deficiency presents early in life with hypotonia, hypokinesia, oculogyric crisis, autonomic dysfunction, dysphoric mood, and sleep disturbance. [aadcresearch.org]

• Psychomotor Retardation

  These patients were born to healthy and non-consanguineous parents, and presented oculogyric crises, paroxysmal dystonic attacks, and severe psychomotor retardation since early infancy. [ncbi.nlm.nih.gov]

• Dystonia

  CONCLUSION: AADC deficiency is a severe neurometabolic disorder, characterized by muscular hypotonia, dystonia, oculogyric crises and additional extraneurological symptoms. [ncbi.nlm.nih.gov]

  Aromatic L-amino acid decarboxylase deficiency Specialty Neurology Symptoms Dystonia, oculogyric crises, developmental delay, parkinsonism, dysautonomia Usual onset Infancy Causes Autosomal recessive DDC mutation Diagnostic method Lumbar puncture for [en.wikipedia.org]

  […] definitions of AADC Samples in periodicals archive: The diseases identified to date include: tyrosine hydroxylase deficiency (TH deficiency); aromatic L-amino acid decarboxylase deficiency (ALADD or AADC); GTP-1 cyclohydrolase deficiency (dopa-responsive dystonia [acronymfinder.com]

• Seizure

  Because an association with epileptic seizures is uncommon in AADC deficiency, some cases may have been regarded as involuntary non-epileptic movements. [ncbi.nlm.nih.gov]

  J Child Neurol 24: 591–9 CrossRef PubMed Google Scholar Plecko B, Stockler S (2009) Vitamin B6 dependent seizures. [link.springer.com]

• Irritability

  Our male patient presented with developmental delay, extreme hypotonia, oculogyric crises, and irritability. [ncbi.nlm.nih.gov]

  Clinical Presentation: symptoms may include temperature instability, ptosis of the eyelids, hypersalivation, distal chorea, swallowing difficulties, drowsiness, irritability, truncal hypotonia, oculogyric crises, pinpoint pupils. [ndrf.org]

  Usually they begin in the afternoon and are characterized by increased irritability, crying, abnormal eye movements, stiffness withabnormal posturing and stridor (rattled breathing). [pndassoc.org]

• Tremor

  Common manifestations Overall hypotonia (including trunk, head and limbs) Rigidity and stiffness Abnormal eye movements (crossing, upward fixed gaze, eyes darting side to side) Ptosis (droopy eyelids) Dystonia Paucity of spontaneous movements Limb tremor [pndassoc.org]

  Affected children may also experience tremors when attempting to hold certain poses or positions (postural tremors) or have abnormal, involuntary eye movements. [rarediseases.org]

  […] and fixation of the eyeballs upwards) Other movement disorders Limb dystonia (disorder of muscle control) Stimulus-provoked dystonia Cervicofacial dystonia Myoclonus/prominent startle Distal chorea Choreoathetosis Athetosis Parkinsonism Flexor spasms Tremor [aadcresearch.org]

  These may occur together with ocular convergence spasm, myoclonic jerks, orofacial dystonia, head drop, torticollis, postural or action tremor, blepharospam or flexor spasms. [jn.nutrition.org]

• Myoclonus

  Here we describe premature twins who presented with severe seizures, myoclonus, rotatory eye movements and sudden clonic contractions. [ncbi.nlm.nih.gov]

  Parasitic Diseases of the Nervous System E-2075 117 Neurologic Complications of Immunization E-2132 118 Paraneoplastic Neurologic Syndromes E-2142 119 ImmuneMediated Epilepsy Movement Disorders and Hashimotos Encephalopathy in Children E-2150 120 Opsoclonus Myoclonus [books.google.de]

  0005964 Irritability Irritable 0000737 Limb dystonia 0002451 Limb hypertonia Increased muscle tone of arm or leg 0002509 Miosis Constricted pupils Pupillary constriction [ more ] 0000616 Muscular hypotonia of the trunk Low muscle tone in trunk 0008936 Myoclonus [rarediseases.info.nih.gov]

  […] limb tone Hypokinesia (decreased spontaneous movements) Oculogyric crises (a spasmodic attack and fixation of the eyeballs upwards) Other movement disorders Limb dystonia (disorder of muscle control) Stimulus-provoked dystonia Cervicofacial dystonia Myoclonus [aadcresearch.org]

Metabolic workup, including thyroid function tests, and determination of ammonia, lactate, and glucose levels and urine amino acids screening yielded nil abnormal. [hkmj.org]

Treatment[edit] There is no cure for aromatic L-amino acid decarboxylase deficiency, but medical and multidisciplinary treatment can relieve some of the symptoms. [en.wikipedia.org]

Therefore, close cardiac monitoring is indicated at baseline and during treatment with pressors. [ncbi.nlm.nih.gov]

Treatment options are limited, in many cases not beneficial, and prognosis is uncertain. [ncbi.nlm.nih.gov]

Diagnosis - Aromatic amino acid decarboxylase deficiency Genetic Testing Registry Prognosis - Aromatic amino acid decarboxylase deficiency Not supplied. [checkorphan.org]

April 13, 2004 ; 62 (7) Views & Reviews Clinical features, treatment, and prognosis R. Pons, B. Ford, C. A. Chiriboga, P. T. Clayton, V. Hinton, K. Hyland, R. Sharma, D. C. [n.neurology.org]

During the 17-hour fast test performed to determine the etiology of her hypoglycemia, insulin and C-peptide were appropriately low, and human GH, IGF-I, cortisol, amino acids, and acylcarnitines were in the usual range for fasting duration. [ncbi.nlm.nih.gov]

To provide a basis for improving the understanding of the epidemiology, genotype–phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry [en.wikipedia.org]

This review article illustrates the pathophysiology, diagnostic methods, and therapeutic strategies for patients with AADC deficiency. [dovepress.com]

[…] trafficking/metabolism may be compromised in AADC deficiency. 5-HTP was demonstrated to potentially be mildly toxic to human neuroblastoma cells but not astrocytoma cells; however the concentrations required for this response are likely to be higher than pathophysiological [discovery.ucl.ac.uk]

Usually, one copy is inherited from each parent.[3] Pathophysiology[edit] The aromatic L-amino acid decarboxylase deficiency enzyme is involved in the synthesis of dopamine and serotonin, both of which are important neurotransmitters. [en.wikipedia.org]

Prevention - Aromatic amino acid decarboxylase deficiency Not supplied. Diagnosis - Aromatic amino acid decarboxylase deficiency Genetic Testing Registry Prognosis - Aromatic amino acid decarboxylase deficiency Not supplied. [checkorphan.org]

OBJECTIVES: To develop a diagnostic platform for preimplantation genetic diagnosis (PGD) and prenatal genetic diagnosis (PND) to prevent births of aromatic L-amino acid decarboxylase deficiency (AADC) patients. [ncbi.nlm.nih.gov]

However inhibiting AADC prevented the GSH increase induced by L-dopa. Furthermore dopamine but not L-dopa, increased GSH release from human astrocytoma cells, which do not express AADC activity. [discovery.ucl.ac.uk]

[…] accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 October 2016 recommending the granting of this designation. the seriousness of the condition; the existence of alternative methods of diagnosis, prevention [ema.europa.eu]

However DDC inhibitors can be used to prevent premature L-DOPA metabolism in the blood, and thereby both increase efficacy and reduce side effects (Burkhard et al., 2001). [novusbio.com]