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Hereditary spastic paraplegia 26(SPG26)

MedGen UID:
373138
Concept ID:
C1836632
Disease or Syndrome
Synonyms: Spastic paraplegia 26; SPASTIC PARAPLEGIA 26, AUTOSOMAL RECESSIVE; SPG26
SNOMED CT: Autosomal recessive spastic paraplegia type 26 (726607007); GM2 synthase deficiency (726607007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): B4GALNT1 (12q13.3)
 
Monarch Initiative: MONDO:0012213
OMIM®: 609195
Orphanet: ORPHA101006

Definition

SPG26 is an autosomal recessive form of complicated spastic paraplegia characterized by onset in the first 2 decades of life of gait abnormalities due to lower limb spasticity and muscle weakness. Some patients have upper limb involvement. Additional features include intellectual disability, peripheral neuropathy, dysarthria, cerebellar signs, extrapyramidal signs, and cortical atrophy. The disorder is slowly progressive (summary by Boukhris et al., 2013). For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800). [from OMIM]

Clinical features

From HPO
Urinary urgency
MedGen UID:
39315
Concept ID:
C0085606
Finding
Urge incontinence is the strong, sudden need to urinate.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
The presence of an unusually high plantar arch. Also called high instep, pes cavus refers to a distinctly hollow form of the sole of the foot when it is bearing weight.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dyskinesia
MedGen UID:
8514
Concept ID:
C0013384
Disease or Syndrome
A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Spastic paraplegia
MedGen UID:
20882
Concept ID:
C0037772
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Spastic gait
MedGen UID:
115907
Concept ID:
C0231687
Finding
Spasticity is manifested by increased stretch reflex which is intensified with movement velocity. This results in excessive and inappropriate muscle activation which can contribute to muscle hypertonia. Spastic gait is characterized by manifestations such as muscle hypertonia, stiff knee, and circumduction of the leg.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Tip-toe gait
MedGen UID:
98104
Concept ID:
C0427144
Finding
An abnormal gait pattern characterized by the failure of the heel to contact the floor at the onset of stance during gait.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Lower limb spasticity
MedGen UID:
220865
Concept ID:
C1271100
Finding
Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis
Abnormal cerebellum morphology
MedGen UID:
400925
Concept ID:
C1866129
Anatomical Abnormality
Any structural abnormality of the cerebellum.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Emotional lability
MedGen UID:
504567
Concept ID:
CN000669
Finding
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or out of proportion to events and circumstances.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Difficulty walking
MedGen UID:
86319
Concept ID:
C0311394
Finding
Reduced ability to walk (ambulate).
Frequent falls
MedGen UID:
163408
Concept ID:
C0850703
Finding
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Decreased serum testosterone concentration
MedGen UID:
892974
Concept ID:
C4073137
Finding
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 26
Follow this link to review classifications for Hereditary spastic paraplegia 26 in Orphanet.

Professional guidelines

PubMed

Kerstens HCJW, Van Lith BJH, Nijkrake MJ, De Swart BJM, Van den Bemd LAC, Smeets RJEM, Klemens F, Van de Warrenburg BPC, Van der Wees PJ, Geurts ACH
Orphanet J Rare Dis 2021 Jun 24;16(1):283. doi: 10.1186/s13023-021-01915-0. PMID: 34167574Free PMC Article
Barlow-Stewart K, Liepins M, Doble A, Otlowski M
Eur J Hum Genet 2018 Sep;26(9):1248-1256. Epub 2018 Jun 11 doi: 10.1038/s41431-018-0198-z. PMID: 29891881Free PMC Article
Zhou YX, Qiao WH, Gu WH, Xie H, Tang BS, Zhou LS, Yang BX, Takiyama Y, Tsuji S, He HY, Deng CX, Goldfarb LG, Wang GX
Arch Neurol 2001 May;58(5):789-94. doi: 10.1001/archneur.58.5.789. PMID: 11346374

Recent clinical studies

Etiology

Rattay TW, Völker M, Rautenberg M, Kessler C, Wurster I, Winter N, Haack TB, Lindig T, Hengel H, Synofzik M, Schüle R, Martus P, Schöls L
Brain 2023 Mar 1;146(3):1093-1102. doi: 10.1093/brain/awac155. PMID: 35472722
Narendiran S, Debnath M, Shivaram S, Kannan R, Sharma S, Christopher R, Seshagiri DV, Jain S, Purushottam M, Mangalore S, Bharath RD, Bindu PS, Sinha S, Taly AB, Nagappa M
J Neurogenet 2022 Mar;36(1):21-31. Epub 2022 May 2 doi: 10.1080/01677063.2022.2064463. PMID: 35499206
De la Casa-Fages B, Fernández-Eulate G, Gamez J, Barahona-Hernando R, Morís G, García-Barcina M, Infante J, Zulaica M, Fernández-Pelayo U, Muñoz-Oreja M, Urtasun M, Olaskoaga A, Zelaya V, Jericó I, Saez-Villaverde R, Catalina I, Sola E, Martínez-Sáez E, Pujol A, Ruiz M, Schlüter A, Spinazzola A, Muñoz-Blanco JL, Grandas F, Holt I, Álvarez V, López de Munaín A
Mov Disord 2019 Oct;34(10):1547-1561. Epub 2019 Aug 21 doi: 10.1002/mds.27812. PMID: 31433872
González-Salazar C, Takazaki KAG, Martinez ARM, Pimentel-Silva LR, Jacinto-Scudeiro LA, Nakagawa ÉY, Fujiwara Murakami CE, Saute JAM, Pedroso JL, Barsottini OGP, Teive HAG, França MC Jr
Eur J Neurol 2019 Apr;26(4):687-693. Epub 2019 Jan 10 doi: 10.1111/ene.13878. PMID: 30489674
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320

Diagnosis

Fereshtehnejad SM, Saleh PA, Oliveira LM, Patel N, Bhowmick S, Saranza G, Kalia LV
Neurol Sci 2023 Mar;44(3):947-959. Epub 2022 Nov 28 doi: 10.1007/s10072-022-06516-8. PMID: 36441344Free PMC Article
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320
Coutinho P, Ruano L, Loureiro JL, Cruz VT, Barros J, Tuna A, Barbot C, Guimarães J, Alonso I, Silveira I, Sequeiros J, Marques Neves J, Serrano P, Silva MC
JAMA Neurol 2013 Jun;70(6):746-55. doi: 10.1001/jamaneurol.2013.1707. PMID: 23609960
Dennis SC, Green NE
J Pediatr Orthop 1988 Jul-Aug;8(4):413-7. doi: 10.1097/01241398-198807000-00006. PMID: 3392192
ROE PF
J Neurol Neurosurg Psychiatry 1963 Dec;26(6):516-9. doi: 10.1136/jnnp.26.6.516. PMID: 14083224Free PMC Article

Therapy

Yang H, Brown RH Jr, Wang D, Strauss KA, Gao G
Trends Mol Med 2021 Jun;27(6):520-523. Epub 2021 Mar 10 doi: 10.1016/j.molmed.2021.02.004. PMID: 33714697Free PMC Article
Pulido-Valdeolivas I, Gómez-Andrés D, Martín-Gonzalo JA, Rodríguez-Andonaegui I, López-López J, Pascual-Pascual SI, Rausell E
PLoS One 2018;13(3):e0192345. Epub 2018 Mar 8 doi: 10.1371/journal.pone.0192345. PMID: 29518090Free PMC Article
Margetis K, Korfias S, Boutos N, Gatzonis S, Themistocleous M, Siatouni A, Dalivigka Z, Flaskas T, Stranjalis G, Boviatsis E, Sakas D
Clin Neurol Neurosurg 2014 Aug;123:142-5. Epub 2014 Jun 4 doi: 10.1016/j.clineuro.2014.05.024. PMID: 24973568
Sankaranarayanan R, Nessa A, Esmy PO, Dangou JM
Best Pract Res Clin Obstet Gynaecol 2012 Apr;26(2):221-32. Epub 2011 Nov 9 doi: 10.1016/j.bpobgyn.2011.08.003. PMID: 22075441
Guidubaldi A, Piano C, Santorelli FM, Silvestri G, Petracca M, Tessa A, Bentivoglio AR
Mov Disord 2011 Feb 15;26(3):553-6. Epub 2011 Mar 4 doi: 10.1002/mds.23552. PMID: 21381113

Prognosis

Rattay TW, Völker M, Rautenberg M, Kessler C, Wurster I, Winter N, Haack TB, Lindig T, Hengel H, Synofzik M, Schüle R, Martus P, Schöls L
Brain 2023 Mar 1;146(3):1093-1102. doi: 10.1093/brain/awac155. PMID: 35472722
Pulido-Valdeolivas I, Gómez-Andrés D, Martín-Gonzalo JA, Rodríguez-Andonaegui I, López-López J, Pascual-Pascual SI, Rausell E
PLoS One 2018;13(3):e0192345. Epub 2018 Mar 8 doi: 10.1371/journal.pone.0192345. PMID: 29518090Free PMC Article
Dad R, Malik U, Javed A, Minassian BA, Hassan MJ
Gene 2017 Aug 30;626:258-263. Epub 2017 May 20 doi: 10.1016/j.gene.2017.05.041. PMID: 28536081
Loureiro JL, Brandão E, Ruano L, Brandão AF, Lopes AM, Thieleke-Matos C, Miller-Fleming L, Cruz VT, Barbosa M, Silveira I, Stevanin G, Pinto-Basto J, Sequeiros J, Alonso I, Coutinho P
JAMA Neurol 2013 Apr;70(4):481-7. doi: 10.1001/jamaneurol.2013.1956. PMID: 23400676
Dennis SC, Green NE
J Pediatr Orthop 1988 Jul-Aug;8(4):413-7. doi: 10.1097/01241398-198807000-00006. PMID: 3392192

Clinical prediction guides

Jacobi H, Weiler M, Sam G, Heiland S, Hayes JM, Bendszus M, Schüle R, Hayes JC
Eur J Neurol 2023 Aug;30(8):2442-2452. Epub 2023 May 26 doi: 10.1111/ene.15841. PMID: 37154411
Rattay TW, Völker M, Rautenberg M, Kessler C, Wurster I, Winter N, Haack TB, Lindig T, Hengel H, Synofzik M, Schüle R, Martus P, Schöls L
Brain 2023 Mar 1;146(3):1093-1102. doi: 10.1093/brain/awac155. PMID: 35472722
De la Casa-Fages B, Fernández-Eulate G, Gamez J, Barahona-Hernando R, Morís G, García-Barcina M, Infante J, Zulaica M, Fernández-Pelayo U, Muñoz-Oreja M, Urtasun M, Olaskoaga A, Zelaya V, Jericó I, Saez-Villaverde R, Catalina I, Sola E, Martínez-Sáez E, Pujol A, Ruiz M, Schlüter A, Spinazzola A, Muñoz-Blanco JL, Grandas F, Holt I, Álvarez V, López de Munaín A
Mov Disord 2019 Oct;34(10):1547-1561. Epub 2019 Aug 21 doi: 10.1002/mds.27812. PMID: 31433872
González-Salazar C, Takazaki KAG, Martinez ARM, Pimentel-Silva LR, Jacinto-Scudeiro LA, Nakagawa ÉY, Fujiwara Murakami CE, Saute JAM, Pedroso JL, Barsottini OGP, Teive HAG, França MC Jr
Eur J Neurol 2019 Apr;26(4):687-693. Epub 2019 Jan 10 doi: 10.1111/ene.13878. PMID: 30489674
Garaci F, Toschi N, Lanzafame S, Meschini A, Bertini E, Simonetti G, Santorelli FM, Guerrisi M, Floris R
Int J Neurosci 2014 Apr;124(4):261-70. Epub 2013 Sep 27 doi: 10.3109/00207454.2013.836705. PMID: 23968121

Recent systematic reviews

Fereshtehnejad SM, Saleh PA, Oliveira LM, Patel N, Bhowmick S, Saranza G, Kalia LV
Neurol Sci 2023 Mar;44(3):947-959. Epub 2022 Nov 28 doi: 10.1007/s10072-022-06516-8. PMID: 36441344Free PMC Article
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320
Loureiro JL, Brandão E, Ruano L, Brandão AF, Lopes AM, Thieleke-Matos C, Miller-Fleming L, Cruz VT, Barbosa M, Silveira I, Stevanin G, Pinto-Basto J, Sequeiros J, Alonso I, Coutinho P
JAMA Neurol 2013 Apr;70(4):481-7. doi: 10.1001/jamaneurol.2013.1956. PMID: 23400676

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