Clinical, Laboratory Data & Outcome Of 7 Patients Affected Of Multiple Acyl-Coa Dehydrogenase Dehydrogenase

Introduction: Multiple Acyl- coA Dehydrogenase Deficiency (MADD) is an autosomal recessive inherited disorder of fatty acid ,aminoacid and choline metabolism caused by defects of electrone transfer flavoprotein (ETF, encoded by ETFA and ETFB genes or ETF-ubiquinone oxidoreductase , encoded by the ETF dehydrogenase (ETFDH) gene, mapped to 15p23-25, 19q13 and 4q33 respectively. The severity varies from a fatal neonatal form of GAII with congenital anomalies (Type I) or without congenital anomalies (Type II) to a mild late onset form of GAII with muscle weakness and pain (Type III). Mutations in ETFDH is known for the late onset form most often responsive to riboflavin treatment and ETFA, ETFB tend to cause neonatal formsMaterials & Methods: This is a descriptive study on clinical, laboratory data & outcome of 7 GAII cases on treatment with Riboflavin, low fat & protein diet .Diagnosis was confirmed by Acyl carnitine profile (MS/MS),Amino acid assays(HPLC),Urine organic acid (GC/MS) and molecular analysis using Next Generation Sequencing (NGS).Results: 7 patients (4 ,3 ), 4 consanguineous; 2/7 type I (conset: 1st day), 2/7 type II (conset:2nd day), 3/7 type III *conset: 6 months & 12 years), diagnostic age: 2 months-13 years, 4/7: neounatal hypoglycemia, 3/7: seizure, 2/7: congenital anomalies 2/7: hypotonia: 3/7, lateonset: 1/3: muscle weakness, 1/3: abdominal pain, 1/3: recurrent myoglobinuria. 4/7: cortical atrophy in brain MRI, 7/7; high liver and muscle enzymes: 7/7: Elevation of C6-C16 and urine glutaric & dicarboxylic acids. Homozygous mutation in ETFDH was discovered in two cases: a case with recurrent myoglobinuria attacks at 13 years with CPK: 14444 IU: c.1130 T> C (p.Leu 377pro) and c.1141 G> C (p.Gly381Arg) in a severe neonatal type II, deceased at 12 months despite vit B2 therapy from 3 months of age. Follow up 1-14 years: 3 other neonatal: impaired development, 3 type III: responded well, only mild high CPK.Conclusion & discussion: We reported ETFH mutation in a fatal neonatal form of MADD who did not respond to riboflavin. Severety depends on the gene defect, enzyme residual activity and early treatment.

کلیدواژه ها:

MADD ، clinical ، molecular