ABSTRACT
CONTEXT: Familial amyloidotic polyneuropathy (FAP) is often misdiagnosed as other neuropathic illnesses. AIM: To highlight the diagnostic "odyssey" in three families of Indian origin with FAP. SETTINGS AND DESIGN: Cross-sectional, hospital-based study. SUBJECTS AND METHODS: Clinical, radiological, and histological features as well as causes for delayed diagnosis were analyzed in genetically confirmed patients with FAP. STATISTICAL ANALYSIS: Descriptive. RESULTS: Age at evaluation ranged from 24 to 42 years and symptom duration from 1 to 10 years. Referral diagnoses included: (i) in patients 1 and 2-familial dysautonomia, Shy-Drager syndrome, and spino-cerebellar ataxia with seizures, (ii) in patient 3-chronic inflammatory demyelinating polyradiculoneuropathy, and (iii) in patient 4-porphyria. In addition, patients 1 and 2 developed leptomeningeal involvement that was mistaken for tubercular meningitis. Reasons for missed diagnosis included: clinician's lack of awareness, not paying sufficient attention to family history, presence of laboratory distractors such as elevated urinary porphyrins, lack of meticulous search for amyloid in the biopsy, and not performing specific stain for amyloid viz. Congo red. Evidence of amyloid in histological studies of nerve and skin supported by genetic variations in transthyretin gene clinched the diagnosis. The variants identified in our cohort included p.Gly73Glu, p.Val71Ala, and p.Val50Met. CONCLUSION: Lack of awareness and meticulous work-up by clinicians and pathologists contributed to delayed diagnosis of FAP. It is important to establish an accurate diagnosis as these patients may be candidates for upcoming therapies.
