Negative [ 99mTc ]Tc ‐ DPD Scintigraphy, Presence of Monoclonal Protein and Biopsy Suggestive of AL Amyloidosis in a Patient With Homozygous p. Ala101Val Transthyretin Gene Variant

Amyloidosis is a rare disease associated with the deposition of misfolded proteins that damage multiple organs, leading to a wide range of symptoms. The most frequently implicated proteins in amyloidosis include immunoglobulin Free Light Chains (FLC), related to AL amyloidosis, and transthyretin (TTR), which is responsible for ATTR amyloidosis. Here, we report the case of a 52-year-old patient with a history of chronic diarrhea, loss of weight, and orthostatic hypotension with imaging-confirmed cardiac amyloidosis (CA). The diagnostic process was notably complex due to elevated serum FLC, negative [99mTc] DPD scintigraphy, and inconclusive immunohistochemical typing of amyloid fibrils in oral mucosa. The ambiguity of the case prompted genetic analysis, which revealed a rare homozygous p.Ala101Val (c.302C>T) variant in the TTR gene, leading to the diagnosis of hereditary ATTRv amyloidosis. During follow-up, sensorimotor neuropathic symptoms developed in addition to the pre-existing autonomic neuropathy; consequently, Tafamidis therapy was initiated, leading to stabilization of the disease. This case report highlights the diagnostic challenges in distinguishing AL from ATTR amyloidosis, simultaneously pointing out the limitations of current noninvasive testing methods. The importance of genetic testing was demonstrated by the identification of a previously reported pathogenic variant. Furthermore, this represents the first documented case of a homozygous variant associated with a prominent cardiological and neurological phenotype. It is crucial to consider amyloidosis in the context of a pattern of cardiovascular and neuropathic manifestations, as well as to employ appropriate diagnostic approaches to establish an accurate diagnosis and guide optimal management.