What is Aromatic L-Amino Acid Decarboxylase Deficiency?

Aromatic L-Amino Acid Decarboxylase Deficiency (AADC) is a rare metabolic disorder, characterized by the lack of the enzyme involved in the decarboxylation of the aromatic amino acids, L-dopa and 5-hydroxytryptophan. Lack of this enzyme means neurotransmitters are blocked from signaling one another appropriately. The neurotransmitters dopamine, norepinepherine, epinepherine (collectively known as catecholamines) and serotinin are deficient in the central nervous system and periphery.

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”. Usually they begin in the afternoon and are characterized by increased irritability, crying, abnormal eye movements, stiffness withabnormal posturing and stridor (rattled breathing). These “Spells” or “Attacks” can last for many hours and to the caregiver this may be a frightening time.

Other symptoms associated with AADC may be mild, moderate or severe and often vary greatly from case to case. The symptoms of AADC are caused by low or absent plasma AADC enzyme activity in the brain and include the following manifestations*:

(*Defined as: common>70% of patients; frequent, 30-70% of patients;unusual, <30% of patients).

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 with attempted voluntary movement
Autonomic dysfunction (blood pressure and body 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
Tongue thrusting
Gastrointestinal symptoms (dysmotility and absorption, gastroesophageal reflux, constipation and diarrhea)
Nasal congestion
Developmental delay
Hypersensitivity to sensory stimuli
Increased startle
Head drops
Torticollis (involuntary deviation of the head and neck)

Frequent manifestations

Breathholding or Apneic Spells
Growth deficiency
Flexor Spasms
Orofacial Dystonia

Unusual manifestations

Endocrine Abnormalities (Hypoglycemia)
Cardiorespiratory arrest
Generalized seizures
Children with AADC are often initially diagnosed with Seizure Disorder, Cerebral Palsy, Congenital Myasthenia and Mitochondrial Disorder.

What causes AADC?

AADC is inherited as an autosomal recessive trait. In recessive disorders, the condition does not occur unless an individual inherits the same defective gene for the same trait from each parent. A child who receives one normal gene and one gene for the disease will be a carrier but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder is 25%. The risk is the same for each pregnancy.

Who gets AADC?

AADC affects males and females in equal numbers. Only 19 cases have been diagnosed throughout the world. The first diagnosed case of AADC was in 1990, since then, through awareness and education, 15 of the 19 patients have been diagnosed in the last 5-6 years. It is suspected that there are many patients either undiagnosed or misdiagnosed.

How is AADC diagnosed?

A diagnosis of AADC is based upon a two stage testing procedure:

STAGE 1

A lumbar puncture (spinal tap) to determine abnormalities of neurotransmitter metabolites. Screening of the cerebrospinal fluid (CSF) should show the following characteristic results for AADC:

a) Elevated levels of L-dopa, 5-hydroxytryptophan (5HTP) and 3-orthomethyldopa (3-o-md).
b) Decreased levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic (5HIAA) levels
The results of Stage 1 will determine whether Stage 2 is appropriate.

Note: Testing for PND’s is not a routine procedure and requires specific guidelines. Should the treating physician or consultant require more information on laboratories please refer to the Pediatric Neurotransmitter Disease Association or contact:

Keith Hyland, PhD
Director of Neurochemistry
Medical Neurogenetics, LLC
One Dunwoody Park
Atlanta, GA
Phone (678) 225-0222
Fax (678) 225-0212
khyland@medicalneurogenetics.com
info@medicalneurogenetics.com

Teodoro Bottiglieri, PhD
Principle Investigator, Director of Neuropharmacology
Adjunct Professor of Biomedical Studies
Baylor University Medical Center
Institute of Metabolic Disease
Phone (214) 820-4748
Fax (214) 820-4853
Web: http://www.baylorhealth.edu/imd/
TeodoroB@BaylorHealth.edu

STAGE 2

Blood samples can determine whether there is low/absent enzyme involved in the decarboxylation of aromatic amino acid. (Refer to “What is AADC” in the brochure). There are again specific guidelines for blood sampling/shipping and adherence is critical to the accurate diagnosis of AADC. For information on how to collect and where to send the samples, or to receive a testing packet please refer to the above information. If possible samples should be collected from all family members.

Note: If abnormalities of neurotransmitter metabolites are displayed in the Stage 1 testing procedure but are not conclusive to AADC, then consideration should be given to other Pediatric Neurotransmitter Diseases.

How is AADC treated?

Presently treatment of AADC involves a variety of medications with varying success from patient to patient. Medication could include any one or combination of the following:

Dopamine Receptor Agonist
Anticholinergic Agents
Antiepileptics
Monoamine Oxidase Inhibitor
Serotonergic Medications
Gastrointestinal Medications
Miscellaneous category
Physical and occupational therapy is recommended. Speech therapy has also been effective in some children. Medical advancements made in gene therapy or stem cell transplantation may someday provide an avenue to cure the disorder.

Selected References

For a complete list of articles on Aromatic L-Amino Acid Decarboxylase Deficiency, please refer to the Online Mendelian Inheritance in Man (OMIM) which is linked below. Before clicking, you will need to enter the following information at the OMIM site:

Key Words: “Aromatic L-Amino Acid Decarbooxylase Deficiency”

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http://www.ncbi.nlm.nih.gov/omim

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