Early and severe amyloidosis in a patient with concurrent familial Mediterranean fever and pseudoxanthoma elasticum

Area of Science:

• Genetics
• Rare diseases
• Biochemistry

Background:

• Familial Mediterranean Fever (FMF) is an autoinflammatory disorder characterized by recurrent fevers and serositis.
• Pseudoxanthoma elasticum (PXE) is a genetic disorder affecting connective tissue, leading to characteristic skin, eye, and vascular changes.
• Amyloidosis is a condition where abnormal proteins build up in organs.

Observation:

• A young woman presented with early-onset, extensive FMF-related amyloidosis and PXE.
• Genetic analysis revealed homozygous mutations: G1042S in the ABCC6 gene (PXE) and M694I in the MEFV gene (FMF).
• Parental consanguinity was noted, consistent with the homozygous mutations.

Findings:

• The patient carried a novel homozygous G1042S mutation in ABCC6 and a homozygous M694I mutation in MEFV.
• ABCC6 deficiency might exacerbate amyloidosis by increasing heparan sulfate deposition.
• ABCC6 deficiency could also reduce the efficacy of colchicine therapy for FMF.

Implications:

• This case highlights a potential gene-gene interaction between ABCC6 and MEFV in disease severity.
• Understanding this interaction could lead to improved diagnostic and therapeutic strategies for patients with co-occurring FMF and PXE.
• Further research into the role of ABCC6 in amyloidogenesis is warranted.