Spectrum of clinical manifestation of methylmalonic acidemia and homocystinuria in a family of six siblings: novel combination of transcobalamin receptor defect (CD320) and cblC deficiency (MMACHC)

Abstract Background Methylmalonic acidemia with homocystinuria is caused by a rare inborn error of vitamin B12 (cobalamin) metabolism. There are four complementation classes cobalamin defects cblC, cblD, cblF, and cblJ that responsible for combined methylmalonic homocystinuria. Case presentation We report case Pakistani family composed six children diagnosed (MMA + HCU). Mutation analysis siblings revealed variable combination c. 394C > T mutation in the MMACHC gene c.262_264del CD320 gene. All had age onset, initial symptomatology, severity disease, response to treatment. The maximum was 6.5 years minimum at birth. spectrum symptoms ranged from subtle learning disability global developmental delay within same family. None them seizure disorder, megaloblastic anemia, visual disturbance, vascular events. defect itself very rare, only 12 cases have been reported so far. cases, homozygous variant c.394C other two heterozygous mutations CD 320 genes. To date, neither such has literature or this compound mutation. Conclusion Our emphasizes diagnosis inherited metabolic disorder child obviates need screen all disorder.