{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:42:22Z","timestamp":1792978942053,"version":"4.5.0"},"reference-count":19,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2021,12,9]]},"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive inherited inborn error of metabolism, which presents with various severity depending on the level of residual enzyme activity. In neonates, it can present with recurrent hypoventilation episodes, persistent encephalopathy with or without microcephaly. MTHFR deficiency also results in hyperhomocysteinemia, homocystinuria and hypomethionemia. We report a male neonate with severe MTHFR deficiency presenting to us on third week of life with progressive encephalopathy, microcephaly, seizures, central hypoventilation. There was similar history in the previous sibling. The patient\u2019s blood lactate, ammonia, tandem mass spectrometry for amino acids and acyl carnitine were normal. He remained encephalopathic with progressive increase in need of respiratory support in spite of supportive treatment and metabolic cocktail consisting of riboflavin, pyridoxine, coenzyme Q and carnitine. This neonate had novel homozygous mutation, which results in MTHFR deficiency. In newborn with hypoventilation or recurrent apnoea with encephalopathy and microcephaly, MTHFR deficiency should be considered as a differential diagnosis. Mutation study helps in confirming diagnosis; however, extended newborn metabolic screening with homocysteine level could help in early diagnosis of these cases.<\/jats:p>","DOI":"10.1136\/bcr-2021-246431","type":"journal-article","created":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T11:46:04Z","timestamp":1641296764000},"page":"e246431","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Hypoventilation and progressive encephalopathy in a neonate with MTHFR deficiency"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6618-1017","authenticated-orcid":false,"given":"Kiran","family":"Vemireddy","sequence":"first","affiliation":[{"name":"Neonatology, Rainbow Children's Hospital, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4316-0517","authenticated-orcid":false,"given":"Nalinikanta","family":"Panigrahy","sequence":"additional","affiliation":[{"name":"Neonatology, Rainbow Children's Hospital, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lokesh","family":"Lingappa","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Rainbow Children's Hospital, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Chirla","sequence":"additional","affiliation":[{"name":"Neonatology, Rainbow Children's Hospital, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,1,4]]},"reference":[{"key":"2025082711061827000_15.1.e246431.1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9418-1"},{"key":"2025082711061827000_15.1.e246431.2","unstructured":"MTHFR methylenetetrahydrofolate reductase [Homo sapiens (human)] - Gene - NCBI, 2021. Available: https:\/\/www.ncbi.nlm.nih.gov\/gene\/4524"},{"key":"2025082711061827000_15.1.e246431.3","unstructured":"Rosenblatt DS . Inherited disorders of folate transport and metabolism. In: Scriver CR , Beaudet AL , Sly S , et al , eds. The metabolic and molecular bases of inherited disease. Seventh ed. New-York: McGraw-Hill, 1995: 3111\u201328."},{"key":"2025082711061827000_15.1.e246431.4","first-page":"100644","article-title":"Clinical presentation of seven patients with methylenetetrahydrofolate reductase deficiency","volume":"25","author":"Aljassim","year":"2020","journal-title":"Mol Genet Metab Rep"},{"key":"2025082711061827000_15.1.e246431.5","unstructured":"The MTHFR gene homepage - Global Variome shared LOVD, 2021. Available: https:\/\/databases.lovd.nl\/shared\/genes\/MTHFR"},{"key":"2025082711061827000_15.1.e246431.6","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1007\/s12098-012-0789-6","article-title":"Congenital central hypoventilation syndrome with Phox2b gene mutation","volume":"79","author":"Lingappa","year":"2012","journal-title":"Indian J Pediatr"},{"key":"2025082711061827000_15.1.e246431.7","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jsmc.2013.10.005","article-title":"Central hypoventilation syndromes","volume":"9","author":"Cielo","year":"2014","journal-title":"Sleep Med Clin"},{"key":"2025082711061827000_15.1.e246431.8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2011.04021.x"},{"key":"2025082711061827000_15.1.e246431.9","doi-asserted-by":"crossref","unstructured":"Sanghvi KP , Bajaj S , Mirani S . A variant in SLC25A4 leads to mitochondrial DNA-Depletion Syndrome-12A causing neonatal hypotonia and hypoventilation. 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