IllnessAmyloidosis, differential diagnosis

NGS +

Amyloidosis occurs when misfolded proteins accumulate and form deposits in the organism, e.g. in the kidney and heart. This may lead to impairment and loss of organ function. Symptoms vary depending on which organs are affected. For example, transthyretin (TTR) amyloidosis is a slowly progressive disease that occurs in the peripheral nervous system and causes peripheral neuropathy. In some cases, the central nervous system is also affected, or the heart, kidneys, eyes and the gastrointestinal tract. The age at which the first symptoms appear varies between the 3.rd-8.th decade. Depending on the mutated genes such as APOA1, GSN, TTR etc., the resulting protein deposits in different organs/tissues each cause widely varying symptomatology. The mode of inheritance is autosomal dominant as in almost all other monogenic amyloidoses. Diagnostic yield data for the hereditary amyloidoses have not yet been collected. If no pathogenic variants are identified in candidate genes, the clinical diagnosis is by no means ruled out.

References: https://www.ncbi.nlm.nih.gov/books/NBK1207/https://link.springer.com/article/10.1007/s00415-019-09688-0

Differential diagnosis should include Charcot-Marie-Tooth hereditary neuropathy, Fabry disease, mitochondrial disorders like e.g. MELAS, hereditary hypertrophic cardiomyopathy as well as multifactorial disorders like diabetic neuropathy, chronic inflammatory demyelinating polyradiculoneuropathy etc.

• Alias: Amyloidosis, hereditary
• Allelic: Afibrinogenemia, congenital (FGA)
• Allelic: ApoA-I + apoC-III deficiency, combined (APOA1)
• Allelic: Apolipoprotein A-II deficiency (APOA2)
• Allelic: Apolipoprotein C-III deficiency (APOC3)
• Allelic: CINCA [chronic infantile neurologic cutaneous + articular] syndrome (NLRP3)
• Allelic: Carpal tunnel syndrome, familial (TTR)
• Allelic: Deafness, AD 34, with/-out inflammation (NLRP3)
• Allelic: Dysfibrinogenemia, congenital (FGA)
• Allelic: Dystransthyretinemic hyperthyroxinemia (TTR)
• Allelic: Familial cold inflammatory syndrome 1 (NLRP3)
• Allelic: Hypercholesterolemia, familial, modifier of (APOA2)
• Allelic: Hyperlipoproteinemia, type Ib (APOC2)
• Allelic: Hypoalphalipoproteinemia, primary, 2, with/-out corneal clouding (APOA1)
• Allelic: Hypodysfibrinogenemia, congenital (FGA)
• Allelic: Immunodeficiency 43 (B2M)
• Allelic: Keratoendothelitis fugax hereditaria (NLRP3)
• Allelic: Macular degeneration, age-related, 11 (CST3)
• Amyloidosis, 3 or more types (APOA1)
• Amyloidosis, Finnish type (GSN)
• Amyloidosis, familial visceral (B2M)
• Amyloidosis, familial visceral (FGA)
• Amyloidosis, hereditary, transthyretin-related (TTR)
• Amyloidosis, renal (LYZ)
• Cerebral amyloid angiopathy (CST3)
• Muckle-Wells syndrome [urticaria-deafness-amyloidosis] (NLRP3)