Clinical, Molecular Data and Outcome of 25 Iranian Patients Affected of Isolated Methylmalonic Aciduria: A case series

Introduction: Isolated Methylmalonic aciduria (MMA) is a rare autosomal recessive disorder caused by a defect in enzyme methylmalonyl coA mutase (mut0or mut-)or its cofactor adenosylcobalamin (cblA,cblB or cblD variant2).Identification of prognostic factors would be useful to prevent disease complications and good long-term follow up.In this study we aim to report a case series of isolated methyl malonic aciduria to explore clinical, molecular characteristics and their outcomeMaterials & Methods: Isolated methyl malonic aciduria patients treated in Research Unit of Iranian National Society for Study on Inborn Errors of Metabolism from 2006 to 2016 entered the study. Diagnosis was made by died blood spot acyl carnitine profile studied with MS/MS and urine organic acid profile studied by GC/MS. Genotyping was done if the family could afford. After standard MMA therapy a retrospective descriptive analysis was done on 25 patients’ data.Results: 25 patients :13 ♀,12♂;23/25 consanguineous(92%);Mean Birth Body Weight:3074(2450-3700 gr);Mean Birth Head Circumference:34.4(32-36 cm);Mean age of onset:10.77(0.1-72 mo);Mean age at diagnosis:17.63(0.6-80 mo) Mean follow up duration:5.44(0.2-23yrs) ;First Presentations: vomitting13/25(52%), Coma4/25(16%), Developmental Delay2/25(8%),Respiratory Distress 2/25(8%), Seizure 1/25(4%),school age low IQ1/25(4%), adolescent major depression 1/25(4%); Mean Hyperammonemic episodes after treatment :3.24(range:0-12); Complications : Permanent Metabolic Acidosis 16/25(64%), Developmental Delay15/25(60%),Lactic Acidosis10/25(40%),Nephropathy4/25(16%), Seizure5/25(20%),Optic Neuropathy 2/25(8%); Mean complication age:3.56(0.5-20 yrs); Mean plasma C3 Level:14.12(4-30,cut off:6μmol/L); Mean Urine MMA: 9799.6(552-32640 mmol/molcr ,NLG&c.284C> A,p.Pro95Gln) &1 in MMAB (p.Gln231Ter,c.691G> T) . Previously reported mutations:2 in MUT gene( 121 Ins T AAT> t AAG and 231 Del C ATA> c ATT),1 in MMAA gene( p.Arg359 Ter,c.1075C> G ),3 in MMAB gene ( p.Arg191Trp, c.571C> T )Conclusion & discussion: Isolated MMA in our Iranian studied group has heterogeneous presentation which needs further study for genotype-phenotype correlation, also it is a fairly good responding disease if treated early in life.

کلیدواژه ها:

MMA ، methylmalonic acidemia ، molecular ، clinical