A 78-year-old woman comes to the office due to tenderness and easy bleeding of the gums when she brushes her teeth. The patient has brushed her teeth twice a day for as long as she can remember and has not experienced these symptoms before. Physical examination shows swollen gingiva that bleed on probing. Her skin findings are shown in the image below.
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Further questioning reveals that the patient lives alone and that her diet consists primarily of tea and toast. Her symptoms are most likely caused by hypoactivity of an enzyme found in which of the following compartments?
Disorders caused by defective collagen synthesis | ||
Disorder | Defining characteristics | Impairment |
Ehlers-Danlos syndrome (types I & II) |
| Mutation in type V collagen |
Osteogenesis imperfecta |
| Mutation in type I collagen |
Scurvy |
| Lack of vitamin C impairs collagen hydroxylation |
This patient likely has vitamin C deficiency (scurvy). In the United States, vitamin C deficiency is seen primarily among malnourished populations, including patients with alcohol use disorder and the elderly. The symptoms of scurvy reflect impaired formation of collagen and include gingival swelling/bleeding, petechiae, ecchymoses, and poor wound healing. Perifollicular hemorrhages and coiled (corkscrew) hairs are also commonly seen.
Collagen synthesis is a complex process that begins with the transcription of collagen genes in the nucleus (Choice E). Collagen α-chains are then synthesized by rough endoplasmic reticulum (RER)-bound ribosomes and directed into the cisternae of the RER. Within the RER, specific proline and lysine residues are post-translationally hydroxylated to hydroxyproline and hydroxylysine by prolyl hydroxylase and lysyl hydroxylase, respectively. Vitamin C is a required cofactor for this post-translational modification. Defective hydroxylation of these residues severely diminishes the amount of collagen secreted by fibroblasts and impairs triple helix stability and covalent crosslink formation.
(Choices A and B) After formation of the triple helix, procollagen molecules are secreted from the cell via the Golgi apparatus. Propeptides at the N- and C-terminals are cleaved by extracellular procollagen peptidase to form insoluble tropocollagen molecules. These monomers then self-assemble into collagen fibrils that are subsequently crosslinked via lysyl oxidase.
(Choices C and D) Lysosomes and mitochondria are not directly involved in the synthesis of collagen.
Educational objective:
The hydroxylation of proline and lysine residues in collagen helps it attain its maximum tensile strength. This process occurs in the rough endoplasmic reticulum and requires vitamin C as a cofactor. Impaired collagen synthesis resulting from vitamin C deficiency (scurvy) can lead to fragile vessels, predisposing to gingival bleeding, ecchymosis, and petechia.