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Rapidly Progressive Spastic Paraplegia Due to Hyperhomocysteinemia in Child with MTHFR Gene Mutation and Mitochondrial Complex I Deficiency: A Rare Association

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, prog...

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Autores principales: Mahale, Rohan R., Gautam, Jyothi, Arunachal, Gautam, Alappati, Sandhya, Varghese, Nibu, Kovoor, Jennifer, Mailankody, Pooja, Padmanabha, Hansashree, Pavagada, Mathuranath
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer - Medknow 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706591/
https://www.ncbi.nlm.nih.gov/pubmed/35018185
http://dx.doi.org/10.4103/jpn.JPN_96_20
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author Mahale, Rohan R.
Gautam, Jyothi
Arunachal, Gautam
Alappati, Sandhya
Varghese, Nibu
Kovoor, Jennifer
Mailankody, Pooja
Padmanabha, Hansashree
Pavagada, Mathuranath
author_facet Mahale, Rohan R.
Gautam, Jyothi
Arunachal, Gautam
Alappati, Sandhya
Varghese, Nibu
Kovoor, Jennifer
Mailankody, Pooja
Padmanabha, Hansashree
Pavagada, Mathuranath
author_sort Mahale, Rohan R.
collection PubMed
description 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%).
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spelling pubmed-87065912022-01-10 Rapidly Progressive Spastic Paraplegia Due to Hyperhomocysteinemia in Child with MTHFR Gene Mutation and Mitochondrial Complex I Deficiency: A Rare Association Mahale, Rohan R. Gautam, Jyothi Arunachal, Gautam Alappati, Sandhya Varghese, Nibu Kovoor, Jennifer Mailankody, Pooja Padmanabha, Hansashree Pavagada, Mathuranath J Pediatr Neurosci Case Report 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%). Wolters Kluwer - Medknow 2021 2021-07-12 /pmc/articles/PMC8706591/ /pubmed/35018185 http://dx.doi.org/10.4103/jpn.JPN_96_20 Text en Copyright: © 2021 Journal of Pediatric Neurosciences https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Case Report
Mahale, Rohan R.
Gautam, Jyothi
Arunachal, Gautam
Alappati, Sandhya
Varghese, Nibu
Kovoor, Jennifer
Mailankody, Pooja
Padmanabha, Hansashree
Pavagada, Mathuranath
Rapidly Progressive Spastic Paraplegia Due to Hyperhomocysteinemia in Child with MTHFR Gene Mutation and Mitochondrial Complex I Deficiency: A Rare Association
title Rapidly Progressive Spastic Paraplegia Due to Hyperhomocysteinemia in Child with MTHFR Gene Mutation and Mitochondrial Complex I Deficiency: A Rare Association
title_full Rapidly Progressive Spastic Paraplegia Due to Hyperhomocysteinemia in Child with MTHFR Gene Mutation and Mitochondrial Complex I Deficiency: A Rare Association
title_fullStr Rapidly Progressive Spastic Paraplegia Due to Hyperhomocysteinemia in Child with MTHFR Gene Mutation and Mitochondrial Complex I Deficiency: A Rare Association
title_full_unstemmed Rapidly Progressive Spastic Paraplegia Due to Hyperhomocysteinemia in Child with MTHFR Gene Mutation and Mitochondrial Complex I Deficiency: A Rare Association
title_short Rapidly Progressive Spastic Paraplegia Due to Hyperhomocysteinemia in Child with MTHFR Gene Mutation and Mitochondrial Complex I Deficiency: A Rare Association
title_sort rapidly progressive spastic paraplegia due to hyperhomocysteinemia in child with mthfr gene mutation and mitochondrial complex i deficiency: a rare association
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706591/
https://www.ncbi.nlm.nih.gov/pubmed/35018185
http://dx.doi.org/10.4103/jpn.JPN_96_20
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