PNPLA2 mutation: a paediatric case with early onset but indolent course

Area of Science:

• Genetics
• Rare Diseases
• Biochemistry

Background:

• Neutral Lipid Storage Disease (NLSD) due to PNPLA2 mutations typically presents in adulthood with severe muscular and cardiac complications.
• It is often differentiated from the pediatric Chanarin-Dorfman syndrome, which has more widespread symptoms.
• Early diagnosis of NLSD in children is uncommon, complicating understanding of its early-stage presentation.

Purpose of the Study:

• To report a unique pediatric case of NLSD with PNPLA2 mutation diagnosed incidentally.
• To describe the long-term clinical course and systemic manifestations in a child with early-onset NLSD.
• To investigate the early pathological findings and genetic basis of NLSD in a pediatric patient.

Main Methods:

• Case report of a pediatric patient with persistent hyperCKemia.
• Muscle biopsy analysis revealing significant lipid storage.
• Genetic testing confirming a homozygous PNPLA2 mutation.
• Long-term clinical follow-up including physical examination and muscular MRI.

Main Results:

• A young child was diagnosed with NLSD via PNPLA2 mutation following incidental hyperCKemia.
• Despite marked early lipid storage, the patient showed no muscle weakness, normal muscular MRI, and no cardiac involvement after 14 years.
• Systemic features, including hearing loss, were observed, suggesting a broader phenotype.

Conclusions:

• Significant lipid accumulation in NLSD can occur very early, even without apparent clinical or imaging muscle involvement.
• PNPLA2 mutations may be associated with multisystem features, overlapping with those seen in Chanarin-Dorfman syndrome.
• This case expands the understanding of the early clinical spectrum and potential systemic involvement in pediatric NLSD.