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Fatty acid hydroxylase-associated neurodegeneration(FAHN)

MedGen UID:
777150
Concept ID:
C3668943
Disease or Syndrome
Synonyms: Dysmyelinating Leukodystrophy and Spastic Paraparesis; Fatty Acid Hydroxylase-Associated Neurodegeneration; Spastic Paraplegia 35
SNOMED CT: Fatty acid hydroxylase associated neurodegeneration (702419001); Dysmyelinating leukodystrophy and spastic paraparesis (702419001); Spastic paraplegia 35 (702419001)
 
Monarch Initiative: MONDO:0017999
OMIM®: 612319
Orphanet: ORPHA329308

Disease characteristics

Fatty acid hydroxylase-associated neurodegeneration (FAHN) is characterized early in the disease course by central nervous system involvement including corticospinal tract involvement (spasticity), mixed movement disorder (ataxia/dystonia), and eye findings (optic atrophy, oculomotor abnormalities), and later in the disease course by progressive intellectual impairment and seizures. With disease progression, dystonia and spasticity compromise the ability to ambulate, leading to wheelchair dependence. Life expectancy is variable. FAHN is considered to be a subtype of neurodegeneration with brain iron accumulation (NBIA). [from GeneReviews]
Authors:
Allison Gregory  |  Sunita Venkateswaran  |  Susan J Hayflick   view full author information

Additional description

From OMIM
Autosomal recessive spastic paraplegia-35 (SPG35) is a complicated form of SPG characterized by childhood onset of gait difficulties due to progressive spastic paraparesis, dysarthria, and mild cognitive decline associated with leukodystrophy on brain imaging. Other variable neurologic features, such as dystonia, optic atrophy, and seizures may also occur (summary by Dick et al., 2010). In addition, some patients with mutations in the FA2H gene have radiographic evidence of neurodegeneration with brain iron accumulation (NBIA), thus expanding the phenotype. Kruer et al. (2010) referred to this phenotypic spectrum of disorders as fatty acid hydrolase-associated neurodegeneration (FAHN). In a detailed report of 19 patients with biallelic FA2H mutations, Rattay et al. (2019) stated that the phenotype was diagnostically consistent with a complicated form of SPG. The authors concluded that FA2H mutations cause a narrow phenotype despite prior attempts to classify it into separately defined disease entities. For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).  http://www.omim.org/entry/612319

Professional guidelines

PubMed

Wilson JL, Gregory A, Kurian MA, Bushlin I, Mochel F, Emrick L, Adang L; BPAN Guideline Contributing Author Group, Hogarth P, Hayflick SJ
Dev Med Child Neurol 2021 Dec;63(12):1402-1409. Epub 2021 Aug 4 doi: 10.1111/dmcn.14980. PMID: 34347296

Recent clinical studies

Etiology

Lumsden DE, Tambirajoo K, Hasegawa H, Gimeno H, Kaminska M, Ashkan K, Selway R, Lin JP
Parkinsonism Relat Disord 2022 Dec;105:103-110. Epub 2022 Nov 11 doi: 10.1016/j.parkreldis.2022.11.006. PMID: 36403506
Wilson JL, Gregory A, Kurian MA, Bushlin I, Mochel F, Emrick L, Adang L; BPAN Guideline Contributing Author Group, Hogarth P, Hayflick SJ
Dev Med Child Neurol 2021 Dec;63(12):1402-1409. Epub 2021 Aug 4 doi: 10.1111/dmcn.14980. PMID: 34347296
Rattay TW, Lindig T, Baets J, Smets K, Deconinck T, Söhn AS, Hörtnagel K, Eckstein KN, Wiethoff S, Reichbauer J, Döbler-Neumann M, Krägeloh-Mann I, Auer-Grumbach M, Plecko B, Münchau A, Wilken B, Janauschek M, Giese AK, De Bleecker JL, Ortibus E, Debyser M, Lopez de Munain A, Pujol A, Bassi MT, D'Angelo MG, De Jonghe P, Züchner S, Bauer P, Schöls L, Schüle R
Brain 2019 Jun 1;142(6):1561-1572. doi: 10.1093/brain/awz102. PMID: 31135052Free PMC Article
Hayflick SJ, Kurian MA, Hogarth P
Handb Clin Neurol 2018;147:293-305. doi: 10.1016/B978-0-444-63233-3.00019-1. PMID: 29325618Free PMC Article
Salomão RP, Pedroso JL, Gama MT, Dutra LA, Maciel RH, Godeiro-Junior C, Chien HF, Teive HA, Cardoso F, Barsottini OG
Arq Neuropsiquiatr 2016 Jul;74(7):587-96. doi: 10.1590/0004-282X20160080. PMID: 27487380

Diagnosis

Hashemi N, Abadi RNS, Alavi A, Rohani M, Ghasemi A, Tavasoli AR
Neurol Sci 2023 Dec;44(12):4359-4362. Epub 2023 Jul 6 doi: 10.1007/s10072-023-06932-4. PMID: 37410270
Wilson JL, Gregory A, Kurian MA, Bushlin I, Mochel F, Emrick L, Adang L; BPAN Guideline Contributing Author Group, Hogarth P, Hayflick SJ
Dev Med Child Neurol 2021 Dec;63(12):1402-1409. Epub 2021 Aug 4 doi: 10.1111/dmcn.14980. PMID: 34347296
Hayflick SJ, Kurian MA, Hogarth P
Handb Clin Neurol 2018;147:293-305. doi: 10.1016/B978-0-444-63233-3.00019-1. PMID: 29325618Free PMC Article
Salomão RP, Pedroso JL, Gama MT, Dutra LA, Maciel RH, Godeiro-Junior C, Chien HF, Teive HA, Cardoso F, Barsottini OG
Arq Neuropsiquiatr 2016 Jul;74(7):587-96. doi: 10.1590/0004-282X20160080. PMID: 27487380
Schneider SA, Bhatia KP
Semin Pediatr Neurol 2012 Jun;19(2):57-66. doi: 10.1016/j.spen.2012.03.005. PMID: 22704258

Therapy

Shepherd H, Heartshorne R, Osman-Farah J, Macerollo A
J Neurol Sci 2024 Feb 15;457:122887. Epub 2024 Jan 26 doi: 10.1016/j.jns.2024.122887. PMID: 38295533
El Otmani H, El Moutawakil B, Daghi M, Fadili O, Slassi I, El Azhari A, Essodegui F, Barrou L, Rafai MA, Lakhdar A
Pediatr Neurol 2023 Nov;148:23-27. Epub 2023 Aug 9 doi: 10.1016/j.pediatrneurol.2023.08.002. PMID: 37651973
Liu J, Ding H, Xu K, Wang D, Ouyang J, Liu Z, Liu R
Sci Rep 2022 Nov 21;12(1):19980. doi: 10.1038/s41598-022-23156-2. PMID: 36411289Free PMC Article
Tai CH, Chou SC, Lin CH, Lee WT, Wu RM, Tseng SH
World Neurosurg 2022 Nov;167:e575-e582. Epub 2022 Aug 19 doi: 10.1016/j.wneu.2022.08.053. PMID: 35995355

Prognosis

Decraene B, Smeets S, Remans D, Ortibus E, Vandenberghe W, Nuttin B, Theys T, De Vloo P
Neuromodulation 2024 Apr;27(3):440-446. Epub 2023 Nov 24 doi: 10.1016/j.neurom.2023.10.187. PMID: 37999699
German A, Jukic J, Laner A, Arnold P, Socher E, Mennecke A, Schmidt MA, Winkler J, Abicht A, Regensburger M
Genes (Basel) 2023 Dec 20;15(1) doi: 10.3390/genes15010014. PMID: 38275596Free PMC Article
Eckhardt M
Int J Mol Sci 2023 Mar 3;24(5) doi: 10.3390/ijms24054908. PMID: 36902339Free PMC Article
Kawaguchi M, Sassa T, Kidokoro H, Nakata T, Kato K, Muramatsu H, Okuno Y, Yamamoto H, Kaname T, Kihara A, Natsume J
Brain Dev 2020 Feb;42(2):217-221. Epub 2019 Dec 16 doi: 10.1016/j.braindev.2019.11.006. PMID: 31837835
Rattay TW, Lindig T, Baets J, Smets K, Deconinck T, Söhn AS, Hörtnagel K, Eckstein KN, Wiethoff S, Reichbauer J, Döbler-Neumann M, Krägeloh-Mann I, Auer-Grumbach M, Plecko B, Münchau A, Wilken B, Janauschek M, Giese AK, De Bleecker JL, Ortibus E, Debyser M, Lopez de Munain A, Pujol A, Bassi MT, D'Angelo MG, De Jonghe P, Züchner S, Bauer P, Schöls L, Schüle R
Brain 2019 Jun 1;142(6):1561-1572. doi: 10.1093/brain/awz102. PMID: 31135052Free PMC Article

Clinical prediction guides

Decraene B, Smeets S, Remans D, Ortibus E, Vandenberghe W, Nuttin B, Theys T, De Vloo P
Neuromodulation 2024 Apr;27(3):440-446. Epub 2023 Nov 24 doi: 10.1016/j.neurom.2023.10.187. PMID: 37999699
German A, Jukic J, Laner A, Arnold P, Socher E, Mennecke A, Schmidt MA, Winkler J, Abicht A, Regensburger M
Genes (Basel) 2023 Dec 20;15(1) doi: 10.3390/genes15010014. PMID: 38275596Free PMC Article
Liu J, Ding H, Xu K, Wang D, Ouyang J, Liu Z, Liu R
Sci Rep 2022 Nov 21;12(1):19980. doi: 10.1038/s41598-022-23156-2. PMID: 36411289Free PMC Article
Kawaguchi M, Sassa T, Kidokoro H, Nakata T, Kato K, Muramatsu H, Okuno Y, Yamamoto H, Kaname T, Kihara A, Natsume J
Brain Dev 2020 Feb;42(2):217-221. Epub 2019 Dec 16 doi: 10.1016/j.braindev.2019.11.006. PMID: 31837835
Hayflick SJ, Kurian MA, Hogarth P
Handb Clin Neurol 2018;147:293-305. doi: 10.1016/B978-0-444-63233-3.00019-1. PMID: 29325618Free PMC Article

Recent systematic reviews

Decraene B, Smeets S, Remans D, Ortibus E, Vandenberghe W, Nuttin B, Theys T, De Vloo P
Neuromodulation 2024 Apr;27(3):440-446. Epub 2023 Nov 24 doi: 10.1016/j.neurom.2023.10.187. PMID: 37999699

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