Spastic Paraplegia 35, Autosomal Recessive (SPG35)

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Disease Ontology 12 DOID:0110786 OMIM® 57 612319 OMIM Phenotypic Series 57 PS303350 MeSH 44 D015419 ICD10 32 G11.4 ICD10 via Orphanet 33 G11.4 G23.0

UMLS via Orphanet 72 C3668943 Orphanet 58 ORPHA171629 ORPHA329308 MedGen 41 C2676236 C3496228 SNOMED-CT via HPO 68 103606006 12184005 128602000 128613002 13746004 16110005 161898004 162116003 165232002 1912002 192967009 193662007 19373007 204043002 21061000119107 22066006 228156007 228158008 229654003 229665008 23133003 246545002 246586009 247578003 252157006 253142006 255314001 258211005 278849000 288939007 29753000 298282001 300471006 302226006 312444006 313307000 32566006 328681008 35489007 366575004 386033004 39055007 394679006 40739000 414564002 420675003 425492002 42658009 46252003 48257004 48694002 54200006 563001 6077001 72042002 75088002 76976005 78667006 8009008 8011004 81756001 84757009 91138005 91175000 95646004 more UMLS 71 C3496228 C3668943

MedlinePlus Genetics : ⁴³ Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a progressive disorder of the nervous system (neurodegeneration) characterized by problems with movement and vision that begin during childhood or adolescence.Changes in the way a person walks (gait) and frequent falls are usually the first noticeable signs of FAHN. Affected individuals gradually develop extreme muscle stiffness (spasticity) and exaggerated reflexes. They typically have involuntary muscle cramping (dystonia), problems with coordination and balance (ataxia), or both. The movement problems worsen over time, and some people with this condition eventually require wheelchair assistance.People with FAHN often develop vision problems, which occur due to deterioration (atrophy) of the nerves that carry information from the eyes to the brain (the optic nerves) and difficulties with the muscles that control eye movement. Affected individuals may have a loss of sharp vision (reduced visual acuity), decreased field of vision, impaired color perception, eyes that do not look in the same direction (strabismus), rapid involuntary eye movements (nystagmus), or difficulty moving the eyes intentionally (supranuclear gaze palsy).Speech impairment (dysarthria) also occurs in FAHN, and severely affected individuals may lose the ability to speak. People with this disorder may also have difficulty chewing or swallowing (dysphagia). In severe cases, they may develop malnutrition and require a feeding tube. The swallowing difficulties can lead to a bacterial lung infection called aspiration pneumonia, which can be life-threatening. As the disorder progresses, some affected individuals experience seizures and a decline in intellectual function.Magnetic resonance imaging (MRI) of the brain in people with FAHN shows signs of iron accumulation, especially in an area of the brain called the globus pallidus, which is involved in regulating movement. Similar patterns of iron accumulation are seen in certain other neurological disorders such as infantile neuroaxonal dystrophy and pantothenate kinase-associated neurodegeneration. All these conditions belong to a class of disorders called neurodegeneration with brain iron accumulation (NBIA).

MalaCards based summary : Spastic Paraplegia 35, Autosomal Recessive, also known as fatty acid hydroxylase-associated neurodegeneration, is related to spastic paraparesis and axonal neuropathy, and has symptoms including seizures, ataxia and urgency of micturition. An important gene associated with Spastic Paraplegia 35, Autosomal Recessive is FA2H (Fatty Acid 2-Hydroxylase), and among its related pathways/superpathways is Pantothenate and CoA biosynthesis. Affiliated tissues include brain, eye and globus pallidus, and related phenotypes are mental deterioration and spastic paraplegia

Disease Ontology : ¹² A hereditary spastic paraplegia that has material basis in mutation in the FA2H gene on chromosome 16q23.1.

GARD : ²⁰ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 329308DefinitionFatty acid hydroxylase-associated neurodegeneration (FAHN) is a very rare, autosomal recessive form of neurodegeneration with brain iron accumulation (NBIA) characterized by childhood-onset focal dystonia, progressive spastic paraplegia that progresses to tetra paresis, ataxia, dysarthria, intellectual decline, and oculomotor disturbances (optic atrophy), accompanied by iron deposition in the globus pallidus.Visit the Orphanet disease page for more resources.

OMIM® : ⁵⁷ Autosomal recessive spastic paraplegia-35 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). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800). (612319) (Updated 05-Mar-2021)

UniProtKB/Swiss-Prot : ⁷³ Spastic paraplegia 35, autosomal recessive: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG35 is a complicated form characterized by childhood onset of gait difficulties. It has a rapid progression and many patients become wheelchair-bound as young adults. Patients manifest cognitive decline associated with leukodystrophy. Other variable neurologic features, such as dystonia, optic atrophy, and seizures may also occur.

GeneReviews: NBK56080

Clinical features from OMIM®:

612319 (Updated 05-Mar-2021)

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