What collagen property defect is likely causing a patient's joint connective tissue degeneration after ingesting sweet pea Lathyrus odoratus?

Defect in Collagen Cross-Linking Due to Lathyrus odoratus Ingestion

The patient's symptoms of joint connective tissue degeneration after ingesting sweet pea (Lathyrus odoratus) are most likely caused by a defect in cross-linking of collagen molecules (option A). This condition represents a form of acquired lathyrism resulting from the inhibition of lysyl oxidase enzyme activity.

Mechanism of Sweet Pea Toxicity

• Sweet pea (Lathyrus odoratus) contains β-aminopropionitrile (BAPN), a lathyrogen that specifically inhibits lysyl oxidase, the enzyme responsible for catalyzing cross-link formation between collagen molecules 1
• BAPN prevents the formation of cross-links between allysine residues in collagen, compromising the structural integrity of connective tissues 1, 2
• This inhibition leads to mechanically weakened collagen that cannot withstand normal physiological stresses, resulting in joint connective tissue degeneration 1

Collagen Cross-Linking Process

• Normal collagen strength depends on the formation of intermolecular cross-links between collagen molecules 2
• Lysyl oxidase converts specific lysine residues to allysine, which then forms cross-links with neighboring collagen molecules 2
• These cross-links are essential for providing tensile strength and stability to collagen fibrils in the extracellular matrix 3
• When cross-linking is impaired, collagen fibrils become disorganized and lose their typical structural arrangement 3

Clinical Manifestations of Impaired Cross-Linking

• Joint connective tissue degeneration is a hallmark of lathyrism due to weakened collagen structure 1
• Skeletal deformities develop as a result of reduced mechanical integrity of the collagenous matrix 1
• The condition may present with symptoms similar to those seen in genetic disorders affecting collagen cross-linking, such as certain forms of Ehlers-Danlos syndrome 4

Differential Diagnosis Among Answer Choices

• Cross-linking of allysine residues (A): This is the correct answer as BAPN directly inhibits lysyl oxidase, preventing the formation of cross-links between allysine residues 1, 2
• Glycosylation (B): While glycosylation is important for collagen function, it is not the primary target of BAPN toxicity 2
• Hydroxylation of proline (C): Proline hydroxylation occurs earlier in collagen synthesis and is catalyzed by prolyl hydroxylase, not lysyl oxidase 2, 3
• Primary sequence (D): The primary amino acid sequence of collagen is determined genetically and is not altered by BAPN exposure 2
• Proteolytic processing (E): Removal of pro-peptides is necessary for collagen fibril formation but is not directly affected by BAPN 2

Clinical Implications

• The patient's symptoms represent an acquired form of collagen dysfunction rather than a genetic disorder 1
• Unlike genetic disorders of collagen such as osteogenesis imperfecta or Bruck syndrome, this condition is potentially reversible if exposure to the toxin is eliminated 2, 3
• Supportive care and prevention of further exposure to the lathyrogen are the primary management approaches 1

In famine situations, consumption of Lathyrus species (including sweet peas) increases due to food scarcity, which can lead to widespread cases of lathyrism with both neurological and musculoskeletal manifestations 1.