vitamin-b-12 and Retinitis-Pigmentosa

Folate and vitamin B(12) metabolism are essential for de novo purine synthesis, and several defects in these pathways have been associated with immunodeficiency. Here we describe the occurrence of severe combined immunodeficiency (SCID) with megaloblastic anemia, leukopenia, atypical hemolytic uremic syndrome, and neurologic abnormalities in which hydroxocobalamin and folate therapy provided partial immune reconstitution. Whole exome sequencing identified compound heterozygous mutations in the MTHFD1 gene, which encodes a trifunctional protein essential for processing of single-carbon folate derivatives. We now report the immunologic details of this novel genetic cause of SCID and the response to targeted metabolic supplementation therapies. This finding expands the known metabolic causes of SCID and presents an important diagnostic consideration given the positive impact of therapy.

Topics: 3-Hydroxyacyl CoA Dehydrogenases; Anemia, Megaloblastic; Bone Marrow Examination; Cardiomyopathies; Combined Modality Therapy; DNA Mutational Analysis; Drug Combinations; Drug Therapy, Combination; Exome; Female; Genetic Carrier Screening; Humans; Hydroxocobalamin; Immunization, Passive; Infant; Infant, Newborn; Leukopenia; Lipid Metabolism, Inborn Errors; Methylenetetrahydrofolate Dehydrogenase (NADP); Minor Histocompatibility Antigens; Mitochondrial Myopathies; Mitochondrial Trifunctional Protein; Nervous System Diseases; Opportunistic Infections; Peripheral Nervous System Diseases; Pneumonia, Pneumocystis; Retinitis Pigmentosa; Rhabdomyolysis; Sequence Analysis, DNA; Severe Combined Immunodeficiency; Sulfadoxine; Trimethoprim; Vitamin B 12

A 63-years-old male with pernicious anemia had been treated for 20 years with weekly injections of iron-dextran and cyanocobalamine. Ophthalmological examination revealed the ophthalmoscopic picture of a tapetoretinal degeneration, reduced visual acuity and narrow visual fields. ERG and dark-adaptation test were normal. Hematological examination including liver and bone marrow biopsies gave no support for the existence of systemic siderosis. It is proposed that the retinal degeneration is due to the extensive parenteral iron treatment with a total dose of approximately 100 grams of iron. This theory is supported by a previous experimental report.

Topics: Aged; Anemia, Pernicious; Drug Therapy, Combination; Fluorescein Angiography; Humans; Injections, Intramuscular; Iron-Dextran Complex; Male; Retinal Degeneration; Retinitis Pigmentosa; Vitamin B 12

Topics: Animals; Electroretinography; Iodine; Male; Rabbits; Retinitis Pigmentosa; Sodium; Vitamin B 12

Topics: Glaucoma; Humans; Niacin; Nicotinic Acids; Retina; Retinitis Pigmentosa; Vitamin B 12