Differential diagnosis of AADC deficiency: Cerebral palsy

What is cerebral palsy?

• Cerebral palsy (CP) is a group of permanent neuromotor disorders causing activity limitations attributed to non-progressive disturbances that occurred in the developing foetal or infant brain, accompanied by developmental delay^1,2
• It is the most common cause of severe physical disability in children, with a prevalence of 1.7–3.1 per 1,000 live births in high-income countries, and a higher prevalence in low-income countries³

Classification of cerebral palsy

There are several forms of CP, classified according to which part of the central nervous system is malformed or damaged and the different manifestations.^4,5

Spastic CP

• Spastic CP is the most common form of the condition, representing >70% of cases. Symptoms include stiff, spastic muscles, abnormal movements, difficulties controlling and coordinating muscle movements, and impairment of oral, lingual and palatal movement, which results in dysarthria and dysphagia. Consequently, patients fail to reach normal milestones for sitting, crawling and walking^4,5

Athetoid or dyskinetic CP

• Athetoid or dyskinetic CP occurs in ~20% of cases and is characterised by slow, writhing movements (athetosis), repetitive, twisting motions (dystonia), and unpredictable, irregular movements (chorea). These abnormal motions can all range from slow to rapid and can be accompanied by pain. Movements may increase with emotional tension and may disappear during sleep^‡4,5

Ataxic CP

• Ataxic CP occurs in less than 5% of cases. Symptoms include weakness, poor coordination, tremors and shaky movements, unsteadiness and balance problems, and difficulty with rapid or fine movement^4,5

Mixed CP

• Mixed CP is a common occurrence whereby patients present with a combination of symptoms. It generally includes spasticity and athetosis^4,5

Overlapping and differentiating symptoms of cerebral palsy and AADC deficiency

• Many of the childhood manifestations of CP are similar to those seen in patients with a monoamine neurotransmitter disorder such as AADC deficiency⁶
• Consequentially, the term ‘CP mimic’ is used to describe a number of neurological disorders that manifest similarly in early childhood²
• Clinical symptoms of AADC deficiency that are atypical in CP include oculogyric crises and diurnal variation of motor symptoms
• Appropriate investigations, including analysis of neurotransmitters in cerebrospinal fluid, are essential for an accurate clinical diagnosis^2,7
• CP mimics also show several features that differ from classic CP and can serve as diagnostic clues, including multiple features of autonomic dysfunction
• Features of autonomic dysfunction include excessive sweating (diaphoresis), temperature instability, profuse nasal and oropharyngeal secretions, poor gut movements (gastrointestinal dysmotility) and sleep disturbances²

Overlapping and differentiating symptoms of CP and AADC deficiency:^*

Workup of patients with cerebral palsy symptoms

• Brain MRI is a first‐line investigation in a child or adult with an undiagnosed motor disorder which suggests CP²
• Brain imaging can readily reveal a cerebral malformation as the main cause of neurological symptoms²
• Aside from cerebral malformation, brain imaging can reveal either normal findings or specific lesions which are characteristic of a genetic disorder or group of disorders, which should prompt further investigation²