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.