Abnormal fat distribution in two patients with RAB7A-associated Charcot-Marie-Tooth type 2B: a case report

Area of Science:

• Genetics
• Neurology
• Metabolic Disorders

Background:

• Charcot-Marie-Tooth disease type 2B (CMT2B) is an inherited neuropathy linked to RAB7A gene variants.
• RAB7A encodes a GTPase crucial for lysosomal and lipid metabolism.
• Altered lipid metabolism is known in CMT2B fibroblasts, but abnormal fat distribution was unreported.

Purpose of the Study:

• To report a novel phenotypic feature in CMT2B.
• To investigate the association between RAB7A variants and abnormal fat distribution.

Main Methods:

• Case report of two sisters with confirmed pathogenic RAB7A variant (NM_004637.6:c.484G>A, p.Val162Met).
• Clinical evaluation including neurological exams, nerve conduction studies, and endocrine workup.
• Imaging studies (MRI) to confirm fat deposition; one patient underwent liposuction.

Main Results:

• Patients presented with classic CMT2B symptoms and atypical fat accumulation (neck, back, abdomen).
• Endocrine and metabolic workup excluded other causes for fat distribution.
• Liposuction provided only partial, temporary relief, with fat accumulation recurring.

Conclusions:

• Abnormal fat distribution may be a novel clinical manifestation of RAB7A-related CMT2B.
• This finding highlights potential lipid dysregulation and systemic effects in CMT2B patients.
• Recognizing this phenotype can improve clinical understanding and management of CMT2B.