EXTRACELLULAR MATRIX

Diseases of collagen defects

Defects in structure or assembly of collagen can have severe consequences because of the widespread distribution and important functions of this family of molecules. Diseases that are associated with mutations in collagen genes are summarized in the table below.

Collagen gene	Pathogenic condition
Col1A1, Col1A2	Ehlers-Danlos type VII Osteogenesis imperfecta
Col2A1	Achondrogenesis II Hypochondrogenesis Spondyloepiphyseal dysplasia congenita Kniest dysplasia Stickler syndrome
Col3A1	Ehlers-Danlos type IV
Col4A3,Col4A4 Col4A5 Col4A5/Col4A6	Alport syndrome (autosomal recessive) Alport syndrome (X-linked) Alport syndrome with leiomyomatosis
Col7A1	Dystrophic forms of epidermolysis bullosa
Col10A1	Schmid type metaphyseal dysplasia
Col11A2	Stickler syndrome

The Ehlers-Danlos syndromes are discussed extensively in Biochemistry. Alport's Syndrome is discussed in the ECM lecture. Other collagen diseases, such as scurvy, can result from dietary deficiencies. Here is more information about scurvy than you ever wanted to know unless, like me, you are interested in life in the British navy during the Napoleanic wars:

The symptoms of the disease called scurvy included gradual weakening, pale skin, sunken eyes, tender gums, muscle pain, loss of teeth, internal bleeding, and the opening of wounds such as sword cuts that had healed many years before. Exhaustion, fainting, diarrhea, and lung and kidney trouble followed. Eventually, the sailor "went to Davy Jones's locker" (naval slang for dying). Illustration from Man-of-War by Stephen Biesty (Dorling-Kindersley, NY, 1993).

As indicated above, scurvy results from a dietary deficiency of Vitamin C. Vitamin C is required for the activity of prolyl hydroxylase, which is responsible for the extensive hydroxylation of prolines in collagens. Deficiencies in proline hydroxylation interfere with the assembly of the procollagen triple-helix, resulting in degradation of the collagen. An understanding of the cause and remedy for scurvy grew out of the experience of British sailors in the 18th century. As indicated in the excerpt below from The Wooden World by Rodger, scurvy was a common problem for sailors on long voyages in which fresh fruits and vegetables were not available:

Scurvy was in some ways a more serious, certainly a more widespread problem. Relatively few men actually died of scurvy except on very long ocean passages, but it effectively limited the time a squadron could stay at sea, and thus directly affected the efficiency of the Service. No strategy of blockade, or any other which depended on keeping squadrons at sea for long periods, was possible in the face of endemic scurvy. The difficulty was to find a cure. Much has been made by medical historians of the work of Dr. James Lind, the great naval physician who first provided experimental proof of the antiscorbutic properties of oranges and lemons, and the Admiralty has been freely castigated for not adopting this remedy at once. In fact Lind's celebrated controlled trial may have occurred by accident, and he does not appear to have appreciated its importance himself, or to have made it very clear to his readers. The value of lemons against scurvy was a commonplace known amongst seafarers for generations, but the fruit was only one of many remedies, good or bad, which neither the naval nor the medical world had any scientific method of sifting. Moreover, lemons were scarce and expensive in northern Europe, and the obvious method of preserving them incidentally destroyed the vitamin.

Fortunately, there was a general understanding among sea officers that scurvy was a dietary disease, caused either by the presence of something harmful in the sailor's diet, or by the absence of something essential, and in either case curable by fresh victuals.

From The Wooden World, pp. 100-101, by N.A.M. Rodger

Note that the use of lemons and limes to combat scurvy was the origin of the nickname widely given to British sailors - limeys.