An Ophthalmologic Mystery Many patients with Cbl-C disease suffer from a characteristic "salt and pepper" pigmentary retinopathy with perimacular degeneration that is progressive in nature despite standard medical therapy.  If retinal degeneration is caused by this particular cobalamin defect, then one would assume that either methylmalonic acid or homocysteine, which both accumulate in this disorder, are the biochemical culprits. Yet, patients that present with severe methylmalonic aciduria alone (Cbl-A, Cbl-B) or severe homocystinuria  alone (Cbl-E, Cbl-G) do not develop retinal lesions.  Clinicians and researchers have thus focused their attention to reduced levels of methionine as a potential casue of this rare form of retinopathy.  At this time, it is not clear whether the decreased "total" level of methionine or the decreased "free" fraction of methionine plays a critical role in retinal integrity.     The Fight for Sight Researchers believe they are on the verge of mapping the exact chromosomal location where children with Cbl-C have their genetic mutation.  Armed with this information, it may be possible to develop an animal model of this rare metabolic defect, which will allow clinicians and researchers to better study the intricacies of cellular cobalamin metabolism and direct therapy in a more targeted fashion.  Unfortunately, because errors in cobalamin metabolism are so rare, there is little NIH support for research that may lead to sight-saving therapeutic interventions.  The Michael Clapcich Fund for Retinal Research is committed to making this type of research a reality.