ATP6AP1-CDG: Follow-up and female phenotype

Area of Science:

• Genetics
• Immunology
• Metabolic disorders

Background:

• X-linked ATP6AP1 deficiency (ATP6AP1-CDG) presents with immunodeficiency, hepatic, gastric, and neurological issues.
• Previous reports detailed additional features like connective tissue abnormalities, hearing loss, and metabolic dysfunction.

Purpose of the Study:

• To describe the long-term follow-up and disease progression in siblings with ATP6AP1-CDG.
• To investigate potential clinical manifestations in female carriers of ATP6AP1-CDG.

Main Methods:

• Longitudinal clinical observation of three affected siblings.
• Clinical evaluation of three female carriers, including serum transferrin isoelectric focusing and urinalysis.

Main Results:

• Siblings exhibited progressive sensorineural hearing loss to total deafness, hair loss (alopecia), skin changes, and proteinuria.
• Female carriers showed normal serum transferrin isoelectric focusing, but two developed persistent proteinuria.

Conclusions:

• ATP6AP1-CDG is a progressive disorder with significant multi-systemic impact.
• Proteinuria may be a manifestation in both affected males and female carriers, warranting further investigation.