Symptoms that mimicked epilepsy led to the misdiagnosis of a Chinese infant girl with aromatic l-amino acid decarboxylase (AADC) deficiency, a case study reported.
The researchers noted the case emphasizes the difficulty distinguishing between epileptic episodes, or seizures, and oculogyric crisis — a common symptom of AADC deficiency marked by the fixed upward gaze of the eyes.
An early and accurate diagnosis can help avoid misdiagnosis and incorrect treatment, they said.
The case study, “Oculogyric crisis mimicked epilepsy in a Chinese aromatic L-amino acid decarboxylase-deficient patient: A case report,” was published in Frontiers in Neurology.
AADC deficiency is marked by reduced activity of the AADC enzyme due to mutations in both copies of the DDC gene. This enzyme deficiency impairs the production of certain neurotransmitters, or signaling molecules essential for nerve cell communication, and many aspects of brain activity. Symptoms vary widely from person to person, mainly due to different levels of these neurotransmitters.
The key symptoms include low muscle tone at an early age, slow movements, involuntary muscle contractions (dystonia), oculogyric crises, developmental delay, drooping eyelids, and excessive sweating.
An oculogyric crisis is an eye movement disorder in which the gaze is involuntarily fixed upward due to eye muscle spasms. During an episode, which can last for hours with the progression of the disease, a patient is unable to move their eyes.
These crises are usually accompanied by an open mouth, protruding tongue, restricted neck movement, and lip-smacking — mimicking in many aspects what happens in epileptic seizures.
Less common neurological symptoms include seizures, sleeping difficulties, and some behavioral problems, such as irritability, excessive crying, and dysphoria, or a profound state of unease or dissatisfaction.
Because of how rare AADC deficiency is — there are only about 120 cases reported — clinical experience with diagnosis and treatment is limited, which can lead to misdiagnosis.
Is the diagnosis mistaken?
Researchers at the Beijing Children’s Hospital, China described the case of a young girl with AADC deficiency who was mistakenly diagnosed with epilepsy.
The girl was the second child of otherwise healthy parents and both pregnancy and delivery were uneventful. Soon after birth, she showed weak sucking ability and feeding difficulties.
By 2.5 months, she began having episodes in which her eyes deviated upwards or to the upper right and her arms and legs stiffened. At first, these occurred two to three times a month, but increased to seven to eight times a month. They usually lasted about five minutes, but sometimes went on for up to 30 minutes.
The episodes were provoked by crying, fatigue, or infection and resolved either spontaneously or by relaxation or sleep.
Episodes of eye deviation worsened at four months, occurring two to three times a day and lasting up to two hours.
The girl was admitted to the hospital under the assumption that she had epilepsy and was treated with anti-epileptic medications, which yielded a limited response.
Further examination revealed she had low muscle tone, limb stiffness, severe developmental delays, poor head control — which she had lost at symptom onset — and was unable to roll over or follow sounds or objects.
She also displayed signs of irritability, excessive crying, sleeping difficulties, dysphoria, drooling, excessive sweating, and drooping eyelids.
Her older brother had also shown similar symptoms at 4 months and was diagnosed with epilepsy and cerebral palsy — a group of disorders that affect movement and muscle tone.
Medication and rehabilitation therapy were ineffective and he died at age 10 with the cause of death being reported by his parents as heart and kidney failure. No genetic tests were conducted on the boy and no other family members were affected.
Genetic testing confirms AADC diagnosis
The girl underwent video-monitored electroencephalogram (EEG) to measure her brain’s electrical activity before, during, and after the eye deviation episodes. No signs of epilepsy-related brain activity were detected, strongly suggesting the episodes were instead oculogyric crises with dystonia.
Analyzes on her blood and cerebrospinal fluid, the liquid surrounding the brain and spinal cord, showed an abnormal neurotransmitter pattern. Blood AADC activity levels were also significantly lower than normal.
AADC deficiency diagnosis was confirmed through genetic tests, which showed a different mutation in each of the two copies of the DDC gene — one inherited from her mother (c.419G>A) and the other from her father (c.1375C>T).
Neither mutation had been described previously. They were both classified as variants with uncertain significance, meaning whether they led to damaging changes in the resulting AADC enzyme is unclear.
After diagnosis, the girl received AADC-related therapies, which improved her sleep and lowered the frequency of oculogyric crises to every three to eight days, lasting one hour.
Follow-up at 18 months of age showed average body growth with oculogyric crisis episodes occurring every seven to eight days and lasting up to two hours.
“However, there was no improvement in her developmental delay,” the researchers wrote, adding that “she still had no head control, voluntary movements, or language.”
“This case emphasized the difficulties and necessity of distinguishing epileptic episodes and oculogyric crisis episodes in patients with AADCD, in which video EEG can help differential diagnosis,” the researchers wrote. “Infants with oculogyric crisis and dystonia, developmental delay, and [low muscle tone] should be considered for AADCD.”