Neurological outcome of methylmalonic acidaemia

Abstract

Objective-To assess the long term outcome of patients with methylmalonic acidaemia in a cross sectional study. Patients-All 35 patients with methylmalonic acidaemia seen at Great Ormond Street Hospital for Children in London, UK between 1970 and 1996 were studied. They were divided into cobalamin responsive (n = 6) and non-responsive (n = 29), and early and late onset groups.Results-There was a significant diVerence between cobalamin responsive and non-responsive groups in severity, survival, and incidence of neurological sequelae. Cobalamin responsive patients had mild disease, irrespective of age at presentation, their neurological complications were less severe, and they are all alive. The cobalamin non-responsive group comprised 19 early and nine late onset patients. The early onset patients had more severe disease at presentation and 14 have died; all late onset patients are alive. There was no significant diVerence in abnormal neurological signs, although early onset patients had a significantly reduced full scale intelligence quotient and poor cognitive outcome. In both groups, abnormal neurological signs continue to increase with age. Conclusions-Cobalamin responsive patients have a better long term outcome. The outcome in the non-responsive patients, particularly the early onset group, remains poor and alternative treatments should therefore be considered early in this group. (Arch Dis Child 1998;78:508-512)

Mutation Analysis of Methylmalonyl CoA Mutase Gene Exon 2 in Egyptian Families: Identification of 25 Novel Allelic Variants

“…Initial management involved protein restriction, correction of metabolic acidosis, infection and electrolyte imbalance, MMA or XMTVI® milk, carnitine 100 mg/kg/day, depovite injection every day for the first three days then taken every two days, biotin tab 5 mg twice daily and IV fluid according to the patient condition (Hörster and Hoffmann, 2004), (Nicolaides et al, 1998). In about eight patients, MMA decreased consistently after treatment; they even returned to normal levels; these approaches match those reported by Hörster and Hoffmann (2004).…”

“…MMA commonly presents early in life with severe metabolic acidosis, recurrent vomiting, dehydration, hepatomegaly, respiratory distress, muscular hypotonia and progressive alteration of consciousness, probably (Fowler et al, 2008). evolving to overwhelming illness, deep coma and death. Severe combined keto-and lactic acidosis, hypoglycemia, neutropenia, hyperglycinemia and hyperammonemia are the most important laboratory features (Baumgartner and Viardot, 1995;Hörster and Hoffmann, 2004;Hörster et al, 2007;Nicolaides et al, 1998;Ogier de Baulny et al, 2005;van der Meer et al, 1996). MMA level in urine ranges from 10 to 20 mmol/mol creatinine in mild disturbances of MMA metabolism to over 20,000 mmol/mol creatinine in severe MCM deficiency (Fowler et al, 2008), (Boulat et al, 2003).…”

Combined liver–kidney transplant for the management of methylmalonic aciduria: A case report and review of the literature

“…Progression to coma is not uncommon. If the patient does not succumb to the initial metabolic decompensation, failure to thrive, developmental retardation, renal failure and metabolic strokes follow [1,[3][4][5][6][7][8][9][10][11][12][13][14].…”

Neurocognitive Phenotype of Isolated Methylmalonic Acidemia

“…5 The disorder is difficult to manage and has a highly variable outcome. [6][7][8][9][10][11][12] Treatment options involve injections of vitamin B 12 in responsive patients 13 ; strict adherence to a low-protein diet; carnitine supplementation; and solid organ transplantation. 14 Neurocognitive and neurologic deficits have been recognized to occur in patients with MMA, 6,8,11 including global developmental delay and hyperkinetic movement disorders secondary to basal ganglia injury.…”