Acute leukoencephalopathy with restricted diffusion (ALERD) in a toddler: A diagnostic challenge unmasking hereditary...

Area of Science:

• Pediatric Neurology
• Neurogenetics
• Rare Diseases

Background:

• Hereditary Sensory Autonomic Neuropathy (HSAN) encompasses a group of rare genetic disorders affecting nerve function.
• HSAN type 4 is characterized by congenital insensitivity to pain, anhidrosis, and intellectual disability.
• Acute Leukoencephalopathy with Restricted Diffusion (ALERD) is a severe neurological condition often associated with infections or metabolic derangements.

Purpose of the Study:

• To describe a case of a toddler presenting with symptoms suggestive of both ALERD and HSAN.
• To investigate the genetic basis of the observed neurological presentation.
• To highlight the diagnostic challenges in differentiating or co-diagnosing these conditions.

Main Methods:

• Clinical case presentation detailing symptoms, examination findings, and disease progression.
• Magnetic Resonance Imaging (MRI) of the brain to identify characteristic white matter abnormalities.
• Exome sequencing to identify genetic variants associated with the patient's condition.

Main Results:

• The patient exhibited severe neurological symptoms including seizures and status epilepticus, alongside features of congenital sensory autonomic neuropathy.
• Brain MRI revealed bilateral symmetrical diffusion restriction in the subcortical white matter, consistent with ALERD.
• Exome sequencing identified compound heterozygous likely pathogenic variants in the NTRK1 gene, confirming a diagnosis of HSAN type 4 presenting as ALERD.

Conclusions:

• HSAN type 4 can present with clinical and radiological features mimicking ALERD, posing significant diagnostic challenges.
• Genetic analysis, specifically exome sequencing, is crucial for accurate diagnosis in complex neurological cases.
• This case underscores the importance of considering genetic neuropathies in the differential diagnosis of pediatric leukoencephalopathies.