Early- vs Late- Onset Phenotypes Of Transthyretin Val30Met Familial Amyloid Polyneuropathy (P2.061)

OBJETIVE: To report the clinical features of two non-related patients from Argentina sharing the same transthyretin-related familial amyloid polyneuropathy (TTR-FAP) Met30 mutation. BACKGROUND: Despite over 100 different TTR gene mutations have been reported to date, the Val30Met-TTR is considered the most frequent variant. Different early and late-onset FAP phenotypes have been described related to Met30 mutation. DESIGN/METHODS: Two patients with TTR-FAP Met30 were analyzed. RESULTS: Patient 1: a 31-year-old man from endemic area consulted for erectile dysfunction and urinary urgency. Few months later, he presented symmetrical burning feet sensation. Pinprick and temperature sense were reduced in stockings distribution. Orthostatic hypotension was observed. NVC/EMG demonstrated a length-dependent symmetric sensory-motor axonal polyneuropathy. Sural nerve biopsy failed to show amyloid deposits. Genetic study confirmed heterozygous Val30Met mutation. The patient is waiting for liver transplantation. Patient 2: a 71- year-old female from a non-endemic area complained of numbness and pain in her extremities. History of hypotiroidism, left carpal tunnel syndrome and CIDP were referred. Examination showed decreased sensation to pinprick and temperature over hands and feet. Vibration and joint position sense were absent at the toes. Weakness of dorsiflexion of the feet and of the wrist flexion/extension was observed. A length-dependent axonal sensory-motor polyneuropathy was demonstrated. Sural nerve biopsy was negative. All lip, abdominal fat and colon biopsies revealed amyloid deposits. Heterozygous Val30Met TTR mutation was confirmed. After 3 years, the patient is wheelchair-bound, suffering of pain crises, autonomic dysfunction and swallowing difficulties. Liver transplantation was not considered. Medication is not still available in Argentina. CONCLUSIONS: Unlike the onset of severe autonomic dysfunction seen in our young patient, the older one showed a disabling motor compromise and late autonomic manifestations. These findings confirm the contrasting initial manifestations when comparing early and late onset FAP sharing the same transthyretin gene mutation. TTR-FAP should be considered in patients with polyneuropathy of unclear origin, despite negative nerve biopsy and absence of family background. Disclosure: Dr. Salutto has nothing to disclose. Dr. Alvarez has nothing to disclose. Dr. Beratti has nothing to disclose. Dr. Barroso has nothing to disclose. Dr. Mazia has nothing to disclose.