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Cobalamin C, D, F, G diseases; methylmalonic aciduria and variable homocystinuria
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
In the presence of defective cofactor synthesis, methylmalonate and homocystine accumulate. The amounts are distinctly less than in methylmalonyl CoA mutase deficiency or cystathionine synthase deficiency (Table 4.2). The diagnosis is usually made by organic analysis of the urine, which detects methylmalonate, the most abundant metabolite. Methylcitrate and 3-hydroxypropionate are also identified in this way. Screening tests for methylmalonate (Chapter 3) are also positive, and the diagnosis may first be suspected in this way. Quantitative assay of the urinary amino acids reveals elevated amounts of homocystine. It is important for this purpose to employ fresh urine.
Diseases of Muscle and the Neuromuscular Junction
Published in John W. Scadding, Nicholas A. Losseff, Clinical Neurology, 2011
Chris Turner, Anthony Schapira
Primary carnitine deficiency may be associated with a myopathy and is caused by defective carnitine uptake. It may be diagnosed in skin fibroblasts or blood leukocytes. Patients respond to carnitine supplementation. Secondary carnitine deficiency occurs in some patients with respiratory chain defects, acyl CoA dehydrogenase deficiencies and methylmalonyl CoA mutase deficiency. Sodium valproate may also deplete carnitine stores. Carnitine-deficient myopathy usually presents in childhood or adolescence with proximal limb weakness, although facial and bulbar weakness may also occur. Muscle biopsy may show increased accumulation of lipid, especially in type 1 fibres.
ZRSR2 mutation in a child with refractory macrocytic anemia and Down Syndrome
Published in Pediatric Hematology and Oncology, 2019
Meghna Srinath, Emily Coberly, Kimberly Ebersol, Kirstin Binz, Katsiaryna Laziuk, William T. Gunning, Barbara Gruner, Richard Hammer, Bindu Kanathezhath Sathi
Because of the megaloblastic picture, amino acid profiling was done which revealed elevated methylmalonic acid level (0.60 nmol mL−1 (<0.40)) with normal homocysteine. Intramuscular B12 and oral folate therapy was started, in addition to pRBC transfusion when Hb was persistently lower than 7 g dL−1. After 6 months of pRBC therapy, the frequency of transfusions increased with persistent normocytic-to-macrocytic anemia (MCV 83.7–95.3 fL) and low iron and ferritin despite continuous iron therapy. There was evidence of chronic fecal occult blood loss; however, a Meckel’s scan, upper and lower gut endoscopies, capsule studies, and RBC nuclear scan revealed only chronic gastritis with no active bleeding source. Absorption of oral iron was found to be normal and testing for pernicious anemia (anti-Intrinsic factor antibody) was negative. Testing for mutations in methylmalonyl-CoA mutase was negative, and the patient did not exhibit other features or symptoms of methylmalonyl-CoA mutase deficiency.