Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

cblB defect is a rare type of methylmalonic aciduria. In this study, a Chinese boy was diagnosed with methylmalonic aciduria cblB type and a novel mutation in the MMAB gene. The clinical presentations, blood acylcarnitines profiles, urine organic acids and genetic features of the patient were reported. The boy presented with fever, feeding difficulty and lethargy at the age of 2 months. Seven days later, he had coma, cold limb, thrombocytopenia, metabolic acidosis and liver damage. His blood propionylcarnitine and urinary methylmalonic acid levels increased significantly, but the plasma total homocysteine level was in the normal range, which supported the diagnosis of isolated methylmalonic aciduria. Gene analysis was performed by direct sequencing. No mutation in the MUT gene was found. However, a reported mutation c.577G>A (p.E193K) and a novel mutation c.562G>A (p.V188M) in the MMAB gene were identified, which confirmed the diagnosis of methylmalonic aciduria cblB type. Progressive clinical and biochemical improvement has been observed after hydroxylcobalamin injection, protein-restricted diet with the supplements of special formula and L-carnitine. He is currently 3 years and 11 months old and has a normal development condition. The phenotypes of the patients with cblB defect are nonspecific. Metabolic analysis and MMAB gene analysis are keys for the diagnosis of the disorder.
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PMID:[A Chinese boy with methylmalonic aciduria cblB type and a novel mutation in the MMAB gene]. 2576 Aug 44

Methylmalonic aciduria (MMA) is an inherited metabolic disease caused by methylmalonyl-CoA mutase deficiency. Early-onset disease usually presents with a neonatal acute metabolic acidosis, rapidly causing lethargy, coma, and death if untreated. Late-onset patients have a better prognosis but develop common long-term complications, including neurological deterioration, chronic kidney disease, pancreatitis, optic neuropathy, and chronic liver disease. Of note, oncogenesis has been reported anecdotally in organic acidurias. Here, we present three novel and two previously published cases of MMA patients who developed malignant liver neoplasms. All five patients were affected by a severe, early-onset form of isolated MMA (4 mut0 , 1 cblB subtype). Different types of liver neoplasms, that is, hepatoblastoma and hepatocellular carcinoma, were diagnosed at ages ranging from infancy to adulthood. We discuss pathophysiological hypotheses involved in MMA-related oncogenesis such as mitochondrial dysfunction, impairment of tricarboxylic acid cycle, oxidative stress, and effects of oncometabolites. Based on the intriguing occurrence of liver abnormalities, including neoplasms, we recommend close biochemical and imaging monitoring of liver disease in routine follow-up of MMA patients.
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PMID:Liver neoplasms in methylmalonic aciduria: An emerging complication. 3126 Jan 14