1/4. nature and nurture in vitamin B12 deficiency.We report on a child in whom severe nutritional vitamin B12 deficiency was exacerbated by a genetic impairment of the folate cycle, causing reduced CSF concentrations of the methyl group donor 5-methyltetrahydrofolate. Some patients with vitamin B12 deficiency may benefit from high dose folic acid supplementation, even if plasma concentrations are high.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
2/4. ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg.In the endoplasmic reticulum (ER) of eukaryotes, N-linked glycans are first assembled on the lipid carrier dolichyl pyrophosphate. The GlcNAc(2)Man(9)Glc(3) oligosaccharide is transferred to selected asparagine residues of nascent polypeptides. Defects along the biosynthetic pathway of N-glycans are associated with severe multisystemic syndromes called congenital disorders of glycosylation. Here, we describe a deficiency in the ALG12 ER alpha1,6-mannosyltransferase resulting in a novel type of glycosylation disorder. The severe disease was identified in a child presenting with psychomotor retardation, hypotonia, growth retardation, dysmorphic features and anorexia. In the patient's fibroblasts, the biosynthetic intermediate GlcNAc(2)Man(7) oligosaccharide was detected both on the lipid carrier dolichyl pyrophosphate and on newly synthesized glycoproteins, thus pointing to a defect in the dolichyl pyrophosphate-GlcNAc(2)Man(7)-dependent ALG12 alpha1,6 mannosyltransferase. Analysis of the ALG12 cDNA in the CDG patient revealed compound heterozygosity for two point mutations that resulted in the amino acid substitutions T67M and R146Q, respectively. The impact of these mutations on ALG12 protein function was investigated in the saccharomyces cerevisiae alg12 glycosylation mutant by showing that the yeast ALG12 gene bearing the homologous mutations T61M and R161Q and the human mutant ALG12 cDNA alleles failed to normalize the growth defect phenotype of the alg12 yeast model, whereas expression of the normal ALG12 cDNA complemented the yeast mutation. The ALG12 mannosyltransferase defect defines a new type of congenital disorder of glycosylation, designated CDG-Ig.- - - - - - - - - - ranking = 0.16666666666667keywords = deficiency (Clic here for more details about this article) |
3/4. biotinidase deficiency: the importance of adequate follow-up for an inconclusive newborn screening result.biotinidase deficiency is an inherited metabolic disorder characterized by inability to recycle protein-bound biotin. It usually presents with ataxia and seizures, though atypical presentations have also been described. We report a 15-month-old boy with profound biotinidase deficiency who presented with laryngeal stridor and subsequently developed severe ataxia and lactic acidosis. Subsequently, it was discovered that the patient's newborn screening test for biotinidase activity had been inconclusive, but confirmatory testing had not been done. brain magnetic resonance imaging showed multiple white matter non-enhancing T2 hyperintensities, which largely resolved following 6 months of biotin therapy; however, there was residual deafness and mental retardation. CONCLUSION: An argument is made for universal newborn screening in biotinidase deficiency and improved mechanisms for follow-up of positive screens, because delay in diagnosis results in irreversible morbidity, newborn screening is cost effective, and early therapy prevents the neurologic sequelae.- - - - - - - - - - ranking = 879.97119774275keywords = biotinidase deficiency, biotinidase, deficiency (Clic here for more details about this article) |
4/4. A new case of dihydropyrimidine dehydrogenase deficiency.We present the clinical and biochemical features of a boy with dihydropyrimidine dehydrogenase deficiency, which seem to underline a disease entity of developmental retardation, epilepsy and muscular hypertonia.- - - - - - - - - - ranking = 0.83333333333333keywords = deficiency (Clic here for more details about this article) |