intrinsic-factor and Growth-Disorders

Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass.

Topics: Animals; Bone Density; Bone Development; Female; Growth; Growth Disorders; Growth Hormone; Insulin-Like Growth Factor I; Intrinsic Factor; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoporosis; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; STAT5 Transcription Factor; Taurine; Vitamin B 12; Vitamin B 12 Deficiency

Coexisting deficiencies of both intrinsic factor (IF) and R binder were identified in an Algerian boy who presented with severe megaloblastic anemia, growth retardation, and neurologic dysfunction with typical features of subacute combined degeneration of the spinal cord. The anemia responded completely to cyanocobalamin and folic acid. IF was absent from gastric juice, but acid secretion and gastric mucosa were normal. R binders were absent from gastric juices as well as from serum, saliva, and polymorphonuclear leukocytes. The patient's father exhibited absence of R binder in his serum with a low serum vitamin B12 level and was asymptomatic. This unique case of simultaneous IF and R binder deficiencies suggests a genetic association between these two functionally and immunologically dissimilar, but structurally close vitamin B12-binding proteins.

Topics: Adolescent; Anemia, Megaloblastic; Gastric Juice; Growth Disorders; Humans; Intrinsic Factor; Male; Pedigree; Saliva; Spinocerebellar Degenerations; Transcobalamins

Topics: Achlorhydria; Anemia, Pernicious; Celiac Disease; Child; Eye Manifestations; Gastric Mucosa; Glossitis; Growth Disorders; Humans; Injections, Intramuscular; Intestinal Mucosa; Intrinsic Factor; Male; Neurologic Manifestations; Paresthesia; Skin Diseases; Skin Manifestations; Vitamin B 12; Vitiligo

Topics: Anemia, Macrocytic; Anemia, Pernicious; Child, Preschool; Female; Growth Disorders; Humans; Intrinsic Factor; Vitamin B 12