Abstract
The cblE disorder is characterized by raegaloblastic anemia of infancy associated with homocystinuria but no methylmalonic aciduria (N Eng J Med 310:686, 1984). Untreated, this disorder results in developmental delay. In cultured fibroblasts from the original proband, there was decreased synthesis of methyl-B12 and decreased methionine biosynthesis. Activity of the methyl-B12-dependent enzyme methionine synthase in cell extracts was decreased only when assayed in the presence of suboptimal reducing conditions (J Clin Invest 74:2149, 1984). We have studied cultured fibroblasts from several additional patients with similar clinical findings. Methyl-B12 synthesis and methionine biosynthesis were decreased. Methionine synthase activity in fibroblast extracts was decreased even under optimal reducing conditions. Complementation studies were carried out using polyethylene glycol-induced fusion of cells frctn these various patients. Methionine biosynthesis was increased 2.21-fold, 2.45-fold and 1.41-fold respectively in fused mixed cultures of cells from the original proband with cblE with cells from 3 of the subsequently diagnosed patients. No complementation occurred between cells from these 3 patients. These results identify two distinct complementation classes and suggest that mutations at more than one locus can give rise to this clinical condition. We have called the new complementation class “cblG”.
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