Methylmalonic acidemia (MMA) with homocystinuria cblD & cblF types - A rare disorder of vitamin Bmetabolism in the western region of India

Abstract

Methylmalonic acidemia (MMA) with homocystinuria cblD & cblF type, a very rare disorder of vitamin B12 metabolism, can result in severe neurological complications in a child. The incidence of combined MMA with homocystinuria cblD & cblF type is estimated as less than 1: 100,000. Mutation analysis by next-generation sequencing (NGS) and validation of the NGS variant by Sanger sequencing, is not only the gold standard in diagnosis of MMA but also, can help in the choice of treatment strategy as B12 responsive or unresponsive. We report a male child initially presented at 10 months of age with poor feeding, delayed growth and no head control (milestone, normally present at 3-4 months). The child on evaluation was diagnosed as a case of MMA with homocystinuria type cblD & cblF, based on investigations such as liquid chromatography-mass spectrometry (LC-MS) and mutation analysis done by next-generation sequencing (NGS) validation with Sanger sequencing. He was treated with vitamin B12 supplements and other supportive conservative therapy. Subsequently, he developed global developmental delay and severe neurological complications, within two years. The child was admitted to the pediatric ICU and he underwent percutaneous endoscopic gastrostomy (PEG) and placed on mechanical ventilation via tracheostomy in situ. Unfortunately, the child did not respond to treatment and succumbed to death, despite all resuscitative measures. The aim of this case report is to create awareness about a clinical presentation associated with a very rare metabolic disorder, MMA with homocystinuria cblD & cblF types and the need for early diagnosis, also, to establish an outline for the treatment in these patients.