Search

Cobalamin C (Cbl-C) defects are inherited autosomal recessive disorders of vitamin B12 (or cyanocobalamin [CNCbl]) metabolism. These defects are caused by mutations in the methylmalonic aciduria and homocystinuria Cbl-C type (MMACHC; MIM # 609831) gene located on chromosome 1p34.1, which catalyzes the reductive decyanation of CNCbl, thus impairing the biosynthesis of 5'-deoxyadenosylcobalamin, adenosylcobalamin, and methylcobalamin. This impairment results in methylmalonic acidemia [MMA; MIM # 277400] combined with hyperhomocysteinemia and hypomethioninemia. Clinically, Cbl-C defects are characterized by a constellation of systemic signs and symptoms, including neurological, cognitive, psychiatric, and thromboembolic events. Retinal phenotypes, including maculopathy, pigmentary retinopathy, and optic atrophy, are common in the early-onset form of the disease, but are rare in its adult-onset counterpart. Administration of hydroxocobalamin (OHCbl), betaine, and folinic acid represents main therapeutic approaches. No proven efficacy has been demonstrated for carnitine and dietary protein restrictions. Although early introduction of OHCbl is crucial, no standardized protocols regarding dose adjustment exist. Despite these measures, the long-term outcome is unsatisfactory especially in patients with early onset, who experience frequent progression of their neurological and ocular impairment. The unfavorable outcome suggests that a better understanding of the pathophysiology of the disease is needed to improve treatment protocols and to develop new therapeutic approaches. [ABSTRACT FROM AUTHOR]

The mucopolysaccharidoses (MPSs) are a group of rare lysosomal storage disorders caused by deficiency of enzymes catalyzing the stepwise degradation of glycosaminoglycans dermatan sulfate, heparan sulfate, keratan sulfate, chondroitin sulfate, and hyaluronic acid. There are seven groups of MPS, which are MPS-I (MPS-I-H or Hurler syndrome; MPS-I-S or Scheie syndrome; and MPS-I-HS or Hurler-Scheie syndrome), MPS- II (Hunter syndrome), MPS-III (Sanfilippo syndrome types A to D), MPS-IV (Morquio syndrome types A and B), MPS-VI (Maroteaux-Lamy syndrome), MPS-VII (Sly syndrome), and MPS-IX (Natowicz syndrome). All are inherited as autosomal recessive diseases, with the exception of Hunter syndrome, which follows an X-linked recessive inheritance pattern. The MPSs affect multiple organ systems (including bone, heart, and visceral organs), leading to organ failure. Involvement of central nervous system occurs only in the forms with heparan sulfate accumulation, that is, MPS-I, MPS-II, MPS-III, and MPS-VII. Therapy is available for MPS-I, MPS-II, MPS-IV, and MPS-VI. This review provides a case-based overview of the different forms of MPS with neurological involvement. [ABSTRACT FROM AUTHOR]