1/8. Cobalamin C disease presenting as hemolytic-uremic syndrome in the neonatal period.Anew case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. A 28-day-old boy presented with failure to thrive, hypotonia, pancytopenia, and features of HUS (microangiopathic hemolytic anemia, thrombocytopenia, and renal failure). The possibility of the diagnosis of an underlying vitamin B12 disorder was prompted by evidence of megaloblastic changes on the peripheral smear and by finding in the literature a suggested association of neonatal HUS with this cobalamin-related metabolic disorder. Amino acid analysis showed elevated homocysteine levels in the plasma and increased levels of both homocysteine and methyl malonic acid in the urine. Diagnosis of cobalamin C disease was confirmed by complementation studies using skin fibroblasts. Therapy included parenteral hydroxocobalamin, carnitine, and leucovorin calcium (folinic acid). Cobalamin C disease should be considered in the diagnosis of patients presenting with HUS in infancy who have unexplained megaloblastosis, pancytopenia, neurologic impairment, and failure to thrive. early diagnosis and institution of therapy may be effective in improving survival and quality of life.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
2/8. Cobalamin C deficiency complicated by an atypical glomerulopathy.Cobalamin C (cbl C) deficiency, an inherited disorder of vitamin B12 metabolism, causes elevated levels of methylmalonic acid and homocysteine and decreased methionine in all body fluids. Renal complications of cbl C disease are thrombotic microangiopathy (TMA), chronic renal failure, tubulointerstitial nephritis and proximal renal tubular acidosis. There is, however, only one case report of primary glomerular pathology, focal segmental glomerulosclerosis, in a cbl C deficient patient. We report a case of an atypical glomerulopathy in a 16-year-old male patient with cbl C deficiency. The glomerulopathy manifested with proteinuria and progressive renal insufficiency. The renal histologic, immunofluorescent and ultrastructural findings were similar, but not identical, to idiopathic membranoproliferative glomerulonephritis (MPGN) but also overlapped with those of a TMA. The serum complement profile was normal; there were scanty glomerular deposits of C3, no deposits of IgG and ultrastructural findings that were similar to those seen in either MPGN type III or a TMA. On the basis of these findings we have designated the renal disease as an atypical glomerulopathy.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
3/8. Multiple vascular abnormalities and a paradoxical combination of vitamin B12 deficiency and thrombocytosis in a case with poems syndrome.POEMS/Crow-Fukase syndrome is a rare multisystem disorder associated with elevated vascular endothelial growth factor (VEGF), which clinically presents with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes. We report a case of poems syndrome due to a gammopathy of undetermined significance with thrombocytosis, vitamin B(12) deficiency, highly elevated VEGF and in addition to glomeruloid angiomas two previously undescribed proliferative vascular lesions: a spinal arteriovenous fistula and a plexogenic pulmonary arteriopathy, which ultimately resulted in lethal pulmonary hypertension. We assume that the high VEGF levels caused the vascular abnormalities observed in our patient.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
4/8. A congenital anomaly of vitamin B12 metabolism: a study of three cases.The clinical and morphologic findings of three patients with metabolic acidosis, methylmalonic aciduria, and homocystinuria are presented. The clinical evolution of the patients was similar and was characterized in the first weeks of life by failure to thrive, hypotonia, and lethargy associated with pancytopenia and hepatic dysfunction, eventually progressing to severe respiratory insufficiency and renal failure consistent with a hemolytic-uremic syndrome. The patients died at 40, 45, and 75 days of age. Biochemical analyses and complementation studies revealed a congenital anomaly of vitamin B12 metabolism (cobalamin C disease). Postmortem morphologic findings in all three cases were dominated by a thrombotic microangiopathy of the kidneys and lungs, diffuse hepatic steatosis, and megaloblastic changes in the bone marrow. A severe gastritis with striking cystic dysplastic mucosal changes and total absence of parietal and chief cells was a consistent finding in all three cases, the rest of the gastrointestinal tract appearing essentially normal. Cobalamin C disease is an intracellular defect of cobalamin metabolism with possible recessive inheritance that can result in multiorgan failure early in life, with a thrombotic microangiopathy and unusual changes in the gastric mucosa.- - - - - - - - - - ranking = 2keywords = life (Clic here for more details about this article) |
5/8. The natural history of retinal degeneration in association with cobalamin C (cbl C) disease.PURPOSE: To describe the association between retinal degeneration and cobalamin C (cblC) disease and to review previously published ophthalmic data regarding cblC disease. methods: Descriptive case series of three patients and compilation of all previously reported cases of cblC disease in the ophthalmic literature. RESULTS: All three new cases presented with macular pigmentary changes and showed attenuation of electroretinographic responses. Sequential ERG (electroretinogram) testing in Case 1 demonstrated ERGs that began at the lower limits of normal and became progressively attenuated over time. CONCLUSIONS: Cobalamin C disease results in progressive retinal degeneration with its onset in the first few months of life and progressing rapidly over the first few years of life.- - - - - - - - - - ranking = 2keywords = life (Clic here for more details about this article) |
6/8. Prenatal vitamin B12 therapy of a fetus with methylcobalamin deficiency (cobalamin E disease).A child presented early in life with homocystinuria and megaloblastic anaemia which responded to hydroxocobalamin (OH-B12) therapy. Mental development has been subnormal since birth. fibroblasts from this patient contained low levels of methylcobalamin (CH3-B12) and incorporated less 14C from labelled 5-methyltetrahydrofolate (14CH3H4PteGlu) into methionine. methionine synthase activity was more thiol-dependent in the patient's fibroblasts than it was in normal cells. Studies on fibroblasts from the parents confirmed that both are heterozygous for this disorder. When the mother became pregnant again, prenatal diagnosis was attempted by use of cultured amniocytes obtained at 16 weeks' gestation. Values for incorporation of 14CH3H4PteGlu into methionine by intact cells and the thiol requirement of methionine synthase were abnormal in these amniocytes but these features did not conclusively identify the fetus at risk as being homozygous for the abnormality. Only 8% of the 57Co vitamin B12 incorporated by the fetal amniocytes was present as CH3-B12 compared with 29% and 40% in two control amniocyte lines and 37% and 32% in fibroblasts from the parents who are obligate heterozygotes. These studies suggested that the fetus had CH3-B12 deficiency. The mother was treated with OH-B12 (1 mg twice weekly, intramuscularly) from 25 weeks' gestation. The baby was clinically normal at birth without any evidence of homocystinuria or anaemia, and has been maintained on OH-B12 (1 mg twice weekly). Studies on fibroblasts from the baby confirmed the diagnosis of CH3-B12 deficiency (cobalamin E disease). At 6 months of age, growth and development remain normal.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
7/8. Toxic amblyopia associated with Crohn's disease.A 71-year-old patient presented with failing vision. She was a life-long smoker who had suffered from Crohn's disease for at least 13 years and had vitamin B12 malabsorption which failed to correct with intrinsic factor. It is suggested that toxic amblyopia be considered in any patient with visual impairment associated with terminal ileal disease.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
8/8. Vitamin B12 deficiency in adolescents and young adults with phenylketonuria.Following several years absence from clinical follow up, an 18-year-old female on diet therapy for phenylketonuria presented with spastic paraparesis, tremor, disorientation, slurred speech, distractibility, deteriorating mental function and megaloblastic anaemia (Hb 64g/l mean corpuscular volume 121). plasma phenylalanine levels were 100-600 mumol/l for the first 18 months of life but thereafter, because of serious psycho-social factors, > 1200 mumol/l. Her diet had strictly excluded all meats, eggs and dairy products but she had been ingesting her medical food (Lofenalac) only irregularly. Further investigation revealed a vitamin B12 level of 65.8 pmol/l (normal 150-670). Treatment with oral B12 quickly corrected her anaemia and there was a gradual improvement in speech, gait, tremor, disorientation and mood but mild spastic diplegia remained. This case prompted us to survey 37 adolescent and young adult phenylketonuria patients in our clinic -28 were on diet therapy, 9 were off (age 11-35 years, mean 21.6 years, 17 males, 20 females). Those on diet were not under ideal metabolic control. Six (16%) had subnormal serum B12 levels (< 150 pmol/l) and another six had borderline low values (150-200 pmol/l). None had specific neurological signs of subacute combined degeneration. serum methylmalonic acid and homocysteine were not measured. On the basis of this survey we recommend that complete blood count, serum B12, RBC folate, methylmalonic acid and homocysteine be routinely measured in adolescents and young adults with phenylketonuria.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |