Child with AADC deficiency misdiagnosed with epilepsy: study

Symptoms that mimicked epilepsy led to the misdiagnosis of a Chinese baby girl with aromatic l-amino acid decarboxylase (AADC) deficiency, according to a case study.

The researchers noted that the case emphasizes the difficulty of distinguishing between epileptic episodes, or seizures, and oculogyric crisis – a common symptom of AADC deficiency marked by upward staring of the eyes.

Early and accurate diagnosis can help avoid misdiagnosis and incorrect treatment, they said.

The case study, “Oculogyric crisis mimicking epilepsy in a Chinese patient with aromatic L-amino acid decarboxylase deficiency: about a casewas published in Frontiers in Neurology.

AADC deficiency is marked by reduced activity of the AADC enzyme due to mutations in both copies of the CDD embarrassed. 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 greatly from person to person, mainly due to different levels of these neurotransmitters.

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The main symptoms include weak muscle tone at an early age, slow movements, involuntary muscle contractions (dystonia), oculogyric crises, developmental delay, droopy eyelids and excessive sweating.

An oculogyric crisis is an eye movement disorder in which the gaze is involuntarily fixed upwards due to spasms of the eye muscles. During an episode, which can last for hours as the disease progresses, a patient is unable to move their eyes.

These seizures are usually accompanied by an open mouth, protruding tongue, restricted neck movement and lip smacking – in many ways mimicking what happens during epileptic seizures.

Less common neurological symptoms include seizures, sleep disturbances, and certain behavioral problems, such as irritability, excessive crying and dysphoria, or a profound state of unease or dissatisfaction.

Due to the rarity of AADC deficiency – there are only around 120 reported cases – clinical experience in diagnosis and treatment is limited, which can lead to misdiagnosis.

A wrong diagnosis

Researchers at Children’s Hospital in Beijing, 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 the pregnancy and delivery were uneventful. Shortly after birth, she showed poor sucking ability and feeding difficulties.

At 2.5 months, she began having episodes in which her eyes deviated upwards or upwards to the right and her arms and legs stiffened. At first, these occurred two to three times a month, but grew to seven to eight times a month. They usually lasted about five minutes, but sometimes lasted up to 30 minutes.

Episodes were brought on by crying, fatigue, or infection and resolved either spontaneously or through relaxation or sleep.

The ocular deviation episodes worsened at four months, occurring two to three times a day and lasting up to two hours.

The girl was admitted to hospital on the assumption that she had epilepsy and was treated with anti-epileptic drugs, which gave a limited response.

Further examination revealed she had poor muscle tone, stiffness in limbs, severe developmental delays, poor head control – which she had lost at the onset of symptoms – and was unable to turn around or follow sounds or objects.

She also showed signs of irritability, excessive crying, trouble sleeping, dysphoria, drooling, excessive sweating and droopy eyelids.

Her older brother had also shown similar symptoms at 4 months old and had been 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 the age of 10, with the cause of death reported by parents as heart and kidney failure. No genetic testing was performed on the boy and no other family members were affected.

Genetic testing confirms diagnosis of AADC

The girl underwent an electroencephalogram (EEG) under video surveillance to measure the electrical activity of her brain before, during and after the ocular deviation episodes. No signs of epilepsy-related brain activity were detected, strongly suggesting that the episodes were instead oculogyric crises with dystonia.

Tests of his blood and cerebrospinal fluid, the fluid surrounding the brain and spinal cord, showed an abnormal neurotransmitter pattern. Blood AADC activity levels were also significantly lower than normal.

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The diagnosis of AADC deficiency was confirmed by genetic testing, which showed a different mutation in each of the two copies of the CDD gene – one inherited from his mother (c.419G>A) and the other from his father (c.1375C>T).

Neither of the two mutations had been previously described. They were both classified as variants with uncertain significance, meaning that they caused damaging changes in the resulting AADC enzyme is unclear.

After the diagnosis, the girl received AADC-related therapies, which improved her sleep and reduced 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 episodes of oculogyric crisis 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 movement, or language.”

“This case highlighted the difficulties and the need to distinguish between epileptic episodes and oculogyric crisis episodes in patients with AADCD, in which video EEG can aid in the differential diagnosis,” the researchers wrote. “Infants with oculogyric crisis and dystonia, developmental delay and [low muscle tone] should be considered for AADCD.

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