Methylmalonic acidemia and hyperglycemia: An unusual association.
ABSTRACT Introduction: Hyperglycemia is an exceptional manifestation of methylmalonic acidemia (MMA). We describe a patient with MMA in whom we observed a hyperglycemia which improved under treatment of the metabolic crisis. Case report: A 14month-old boy presented with an acute generalized dystonia and lethargy preceded by fever, vomiting and lethargy at the age of 13months. Biological investigations showed a hyperglycemia, a lactic acidosis and a hyperammonemia. Urinary organic acid analysis showed accumulation of methylmalonic acid, tiglylglycine and methylcitrate leading to the diagnosis of MMA. The patient underwent symptomatic treatment with rapid improvement of general condition, consciousness and gradual normalization of biological parameters especially glycemia after 6days without using insulinotherapy. Discussion: MMA is an autosomal recessive disorder caused by a deficiency of methylmalonyl-CoA mutase resulting in methylmalonic acid accumulation. Biochemically, the disorder is typically characterized by: metabolic acidosis, ketonemia or ketonuria, hyperammonemia, leukopenia, thrombocytopenia and anemia. Hypoglycemia is a frequent manifestation of MMA. Our patient presented a hyperglycemia, which is unusual in MMA, since we found only three patients reported with this association. Pathophysiology remains unknown. In reported cases, hyperglycemia was treated by insulin therapy and reducing glucose intravenous infusion, with fatal outcome. In our patient glycemia spontaneously normalized after treatment of the metabolic crisis. Conclusion: Hyperglycemia is an exceptional manifestation of MMA and could be a seriousness marker.
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ABSTRACT: We describe a case of neonatal methylmalonic acidemia with the unusual complication of severe, insulin-resistant hyperglycemia. Methylmalonic acidemia, an inherited metabolic disease affecting the catabolism of propionic acid, is manifested by persistent metabolic acidosis, urinary excretion of large amounts of methylmalonic acid, and occasionally by hypoglycemia. Severe and persistent metabolic acidosis and hyperglycemia, despite large doses of insulin, were observed in this infant, who excreted large amounts of methylmalonic acid. The diagnosis of methylmalonic acidemia was confirmed by gas chromatography-mass spectroscopy, but the patient died before the defect in glucose tolerance could be delineated. We hypothesize that, in addition to the methylmalonic acidemia, the patient may have had an insulin-receptor defect, which was manifested as an inappropriate response to endogenous and exogenous insulin.Clinical Chemistry 09/1982; 28(8):1801-3. · 7.77 Impact Factor
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ABSTRACT: Isodisomy (ID) is a genetic anomaly defined as the inheritance of two copies of the same genetic material from one parent. ID in an offspring is a rare cause of recessive genetic diseases via inheritance of two copies of a mutated gene from one carrier parent. We studied a newborn female with a mut(o) of methylmalonic acidemia and complete absence of insulin-producing beta cells in otherwise normal-appearing pancreatic islets, causing insulin-dependent diabetes mellitus. The patient died 2 wk after birth. Serotyping of the HLA antigens, DNA typing of HLA-B and HLA class II loci, study of polymorphic DNA markers of chromosome 6, and cytogenetic analysis demonstrated paternal ID, involving at least a 25-centiMorgan portion of the chromosome pair that encompasses the MHC. ID probably caused methylmalonic acidemia by duplication of a mutated allele of the corresponding gene on the chromosome 6 inherited from the father. It is also very likely that ID was etiologically related to the agenesis of beta cells and consequent insulin-dependent diabetes mellitus in our patient. We thus speculate on the existence of a gene on chromosome 6 involved in beta cell differentiation.Journal of Clinical Investigation 08/1994; 94(1):418-21. · 13.77 Impact Factor
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ABSTRACT: To alert the physicians to the possibility of a late-onset inborn error of metabolism in an apparently previously healthy patient with acute clinical presentation. Case report. Pediatric unit and general intensive care unit. An apparently previously healthy 12-yr-old female presented acutely with vomiting, fever, bronchopneumonia, and progressive loss of consciousness associated with ketoacidosis, hyperglycemia, and hyperammonemia. She died 3 days later with a diagnosis of insulin-dependent diabetes mellitus. Intravenous hydration, glucose and insulin, mechanical ventilation. Organic acid analysis on a postmortem sample of aqueous humor revealed high levels of methylmalonic acid. Enzymatic studies on cultured fibroblasts were consistent with the diagnosis of cblB methylmalonic aciduria. The diagnosis of cblB methylmalonic aciduria was made in a postmortem patient who died with a misdiagnosis of insulin-dependent diabetes mellitus. Unclear biochemical findings and positive family history should strongly lead to suspicion of an inborn error of metabolism in an apparently previously healthy critically ill patient.Critical Care Medicine 07/2000; 28(6):2119-21. · 6.15 Impact Factor