Differential diagnosis of AADC deficiency: Neuromuscular disorders

What are neuromuscular disorders?

• Neuromuscular disorders are a broad group of genetic heterogeneous diseases that impair muscle function and/or the peripheral nervous system^1–3
• Impairment can arise in cell bodies (i.e. amyotrophic lateral sclerosis [ALS] or sensory ganglionopathies), axons (i.e. axonal peripheral neuropathies or brachial plexopathies), Schwann cells (i.e. chronic inflammatory demyelinating polyradiculoneuropathy), neuromuscular junctions (i.e. myasthenia gravis or Lambert-Eaton myasthenic syndrome), muscle tissue (i.e. inflammatory myopathy or muscular dystrophy), or at any combination of these sites⁴
• Neuromuscular disorders vary in disease course and severity,⁵ depending on the body area affected. Typical symptoms include muscle weakness, abnormal or impaired ambulation, joint contractures, skeletal deformities, altered sensory perception (in neuropathies) and respiratory failure¹
• Myalgia, rhabdomyolysis and fatigable weakness may occur with normal intervening muscle function, or in individuals with persistent neuromuscular manifestations¹

Types of neuromuscular disorders

Types of neuromuscular disorders include (not an exhaustive list):^1,6

• ALS
• Charcot-Marie-Tooth disease
• Multiple sclerosis
• Muscular dystrophy
• Myasthenia gravis
• Myopathy
• Myositis, including polymyositis and dermatomyositis
• Peripheral neuropathy
• Spinal muscular atrophy

Overlapping and differentiating symptoms of neuromuscular disorders and AADC deficiency

• The majority of patients with AADC deficiency present with movement disorders (hypokinesia, chorea, dystonia, ballismus, dyskinesia, tremor, myoclonus). AADC deficiency can mimic many neuromuscular disorders, such as congenital myasthenia gravis, leading to challenges in diagnosis^7–9

Overlapping and differentiating symptoms of neuromuscular disorders and AADC deficiency: