Rapidly progressive spastic paraplegia due to hyperhomocysteinemia in child with MTHFR gene mutation and mitochondrial Complex I deficiency: A rare association

Abstract

A BSTRACT MTHFR enzyme deficiency is an autosomal-recessive inborn error of folate metabolism. The deficiency cause defect in the remethylation of homocysteine to methionine leading to increased blood levels of homocysteine. Hyperhomocysteinemia in infants cause seizures, hypotonia, apnoea, microcephaly, progressing to coma and death if untreated whereas in childhood onset it causes developmental delay, seizures, psychiatric disturbances, spastic gait, and ataxia. We report a 10-year-old girl with rapidly progressive spastic paraplegia requiring wheelchair ambulation within 3 months of symptom onset with behavioral disturbances. Plasma homocysteine and plasma lactate were high with normal vitamin B12 levels. Clinical exome sequencing showed homozygous missense mutation in MTHFR gene which was likely pathogenic variant. Respiratory chain complex assay from muscle sample showed reduced complex 1 deficiency (<20%).

A Treatable Leukodystrophy Presenting as Familial Spastic Paraparesis with Homozygous Variation in MTHFR Gene- A Case Report

“…Serum homocysteine was high with low vitamin B12 levels. Genetic testing showing a homozygous missense variation in the exon 2 of MTHFR gene (c.459C>G) (p.lle153Met) [5]. He was diagnosed to have methylene tetrahydrofolate reductase deficiency Mahale R et al5 in India observed similar kind of case report in child with rapidly progressive spastic paraplegia and behavioural disturbance of 3 month duration.…”