Sibling phenotype concordance in classical infantile Pompe disease

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Pompe disease, a lysosomal storage disorder caused by acid-alpha-glucosidase deficiency, presents a wide clinical spectrum.
• While late-onset Pompe disease exhibits sibling phenotype discordance, this has not been systematically studied in the infantile form.
• Infantile Pompe disease is characterized by severe symptoms, rapid progression, and early mortality.

Purpose of the Study:

• To investigate phenotypic and lifespan variability among siblings with infantile Pompe disease.
• To compare the clinical course between probands and affected siblings in infantile Pompe disease.
• To provide essential prognostic information for families affected by infantile Pompe disease.

Main Methods:

• A comprehensive review of medical literature was conducted to identify affected sibships with infantile Pompe disease.
• Inclusion criteria required clinical, pathological, or biochemical confirmation of infantile Pompe disease, including early onset, hypotonia, and cardiomegaly.
• Data on age at symptom onset, age at death, and disease course were extracted and compared between probands and affected siblings.

Main Results:

• Thirteen families comprising 31 infants with infantile Pompe disease were identified from publications since 1931.
• A significant correlation was observed between probands and affected siblings regarding the age at symptom onset (median 3 months).
• Minimal phenotypic and lifespan variation was noted among siblings with infantile Pompe disease, with a median disease course of 3 months.

Conclusions:

• Siblings with infantile Pompe disease demonstrate remarkable consistency in disease onset, progression, and lifespan.
• Phenotypic similarity in infantile Pompe disease contrasts with the variability seen in late-onset forms.
• These findings are critical for accurate genetic counseling and family support regarding infantile Pompe disease prognosis.