Rapidly Progressive White Matter Involvement in Early Childhood: The Expanding Phenotype of Infantile Onset Pompe?

Area of Science:

• Neurology
• Metabolic Disorders
• Genetics

Background:

• Glycogen accumulation in the central nervous system is a known feature of infantile onset Pompe disease (IOPD).
• Progressive white matter disease and intellectual decline have been recently recognized as potential complications in IOPD patients.
• Early diagnosis and intervention are crucial for managing rare genetic disorders.

Purpose of the Study:

• To report a case of early-onset progressive central nervous system involvement in a CRIM-negative IOPD patient.
• To investigate potential alternative pathologies given the early symptom onset and familial history.
• To review existing literature on white matter disease in IOPD and discuss underlying mechanisms.

Main Methods:

• Clinical case presentation of a patient with infantile onset Pompe disease.
• Neurological examination and imaging (radiology) to assess central nervous system involvement.
• Biochemical and genetic investigations to rule out alternative diagnoses.
• Literature review of previous radiological and post-mortem findings in IOPD.

Main Results:

• A CRIM-negative IOPD patient, treated with rituximab and methotrexate, developed progressive spasticity and central nervous system involvement by age 4.
• Despite initial response to enzyme replacement therapy (ERT), the patient exhibited evolving neurological symptoms.
• Extensive investigations did not reveal alternative pathologies, suggesting CNS involvement as part of the IOPD spectrum.

Conclusions:

• This case underscores the potential for early-onset and progressive white matter disease in infantile onset Pompe disease, even with treatment.
• The findings necessitate a re-evaluation of the long-term neurological impact of IOPD and its management.
• Further research into the mechanisms of CNS involvement in IOPD is warranted to improve patient outcomes.