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Adult polyglucosan body disease(APBN)

MedGen UID:
342338
Concept ID:
C1849722
Disease or Syndrome
Synonyms: APBN; Polyglucosan body disease, adult form
SNOMED CT: Adult polyglucosan body disease (721099001); Polyglucosan body disease adult form (721099001)
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): GBE1 (3p12.2)
 
Monarch Initiative: MONDO:0009897
OMIM®: 263570
Orphanet: ORPHA206583

Disease characteristics

Excerpted from the GeneReview: GBE1 Adult Polyglucosan Body Disease
Most individuals with classic GBE1 adult polyglucosan body disease (GBE1-APBD) present after age 40 years with unexplained progressive neurogenic bladder, gait difficulties (i.e., spasticity and weakness) from mixed upper and lower motor neuron involvement, sensory loss predominantly in the distal lower extremities, autonomic dysfunction (associated with orthostatic hypotension and constipation), and mild cognitive difficulties (often executive dysfunction). Some affected individuals without classic GBE1-APBD have atypical phenotypes including Alzheimer disease-like dementia and axonal neuropathy, stroke-like episodes, and diaphragmatic failure; others may have a history of infantile liver disease. [from GeneReviews]
Authors:
H Orhan Akman  |  Alexander Lossos  |  Or Kakhlon   view full author information

Additional descriptions

From OMIM
Adult polyglucosan body neuropathy (APBN) is a late-onset, slowly progressive disorder affecting the central and peripheral nervous systems. Patients typically present after age 40 years with a variable combination of cognitive impairment, pyramidal tetraparesis, peripheral neuropathy, and neurogenic bladder. Other manifestations include cerebellar dysfunction and extrapyramidal signs. The pathologic hallmark of the disorder is the widespread accumulation of round, intracellular polyglucosan bodies throughout the nervous system, which are confined to neuronal and astrocytic processes (summary by Lossos et al., 1998).  http://www.omim.org/entry/263570
From MedlinePlus Genetics
Adult polyglucosan body disease (APBD) is a condition that affects the nervous system. People with APBD typically first experience signs and symptoms related to the condition between ages 35 and 60. Initial symptoms of the disorder include numbness and tingling in the legs (peripheral neuropathy) and progressive muscle weakness and stiffness (spasticity). As a result, affected individuals can have an unsteady gait, poor balance, and an increased risk of falling.

Damage to the nerves that control bladder function, a condition called neurogenic bladder, is another feature that often occurs early in the course of APBD. Affected individuals have increasing difficulty starting or stopping the flow of urine.

Eventually, most people with APBD lose the ability to control their bladder and bowel functions and their limbs. Damage to the autonomic nervous system, which controls body functions that are mostly involuntary, leads to problems with blood pressure, heart rate, breathing rate, digestion, temperature regulation, and sexual response, and results in daily bouts of exhaustion. About half of people with APBD experience a decline in intellectual function (dementia).  https://medlineplus.gov/genetics/condition/adult-polyglucosan-body-disease

Clinical features

From HPO
Urinary incontinence
MedGen UID:
22579
Concept ID:
C0042024
Finding
Loss of the ability to control the urinary bladder leading to involuntary urination.
Neurogenic bladder
MedGen UID:
595
Concept ID:
C0005697
Disease or Syndrome
A type of bladder dysfunction caused by neurologic damage. Neurogenic bladder can be flaccid or spastic. Common manifestatios of neurogenic bladder are overflow incontinence, frequency, urgency, urge incontinence, and retention.
Absent Achilles reflex
MedGen UID:
108240
Concept ID:
C0558845
Finding
Absence of the Achilles reflex (also known as the ankle jerk reflex), which can normally be elicited by tapping the tendon is tapped while the foot is dorsiflexed.
Orthostatic hypotension
MedGen UID:
43803
Concept ID:
C0020651
Disease or Syndrome
A form of hypotension characterized by a sudden fall in blood pressure that occurs when a person assumes a standing position.
Paresthesia
MedGen UID:
14619
Concept ID:
C0030554
Disease or Syndrome
Abnormal sensations such as tingling, pricking, or numbness of the skin with no apparent physical cause.
Spastic paraplegia
MedGen UID:
20882
Concept ID:
C0037772
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
Tetraparesis
MedGen UID:
78731
Concept ID:
C0270790
Finding
Weakness of all four limbs.
Cognitive impairment
MedGen UID:
90932
Concept ID:
C0338656
Mental or Behavioral Dysfunction
Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
Abnormal cerebral white matter morphology
MedGen UID:
181756
Concept ID:
C0948163
Pathologic Function
An abnormality of the cerebral white matter.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
Increased CSF protein concentration
MedGen UID:
329971
Concept ID:
C1806780
Finding
Increased concentration of protein in the cerebrospinal fluid.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Abnormal upper motor neuron morphology
MedGen UID:
871241
Concept ID:
C4025723
Anatomical Abnormality
Any structural anomaly that affects the upper motor neuron.
Muscle spasm
MedGen UID:
52431
Concept ID:
C0037763
Sign or Symptom
Sudden and involuntary contractions of one or more muscles.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAdult polyglucosan body disease
Follow this link to review classifications for Adult polyglucosan body disease in Orphanet.

Professional guidelines

PubMed

Koch RL, Soler-Alfonso C, Kiely BT, Asai A, Smith AL, Bali DS, Kang PB, Landstrom AP, Akman HO, Burrow TA, Orthmann-Murphy JL, Goldman DS, Pendyal S, El-Gharbawy AH, Austin SL, Case LE, Schiffmann R, Hirano M, Kishnani PS
Mol Genet Metab 2023 Mar;138(3):107525. Epub 2023 Jan 25 doi: 10.1016/j.ymgme.2023.107525. PMID: 36796138

Recent clinical studies

Etiology

Koch RL, Soler-Alfonso C, Kiely BT, Asai A, Smith AL, Bali DS, Kang PB, Landstrom AP, Akman HO, Burrow TA, Orthmann-Murphy JL, Goldman DS, Pendyal S, El-Gharbawy AH, Austin SL, Case LE, Schiffmann R, Hirano M, Kishnani PS
Mol Genet Metab 2023 Mar;138(3):107525. Epub 2023 Jan 25 doi: 10.1016/j.ymgme.2023.107525. PMID: 36796138
Carneiro I, Rodrigues M, Costa AJ, Cadilha R, Lima A
Rehabilitacion (Madr) 2021 Apr-Jun;55(2):161-163. Epub 2020 Oct 31 doi: 10.1016/j.rh.2020.06.009. PMID: 33139012
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065
Hellmann MA, Kakhlon O, Landau EH, Sadeh M, Giladi N, Schlesinger I, Kidron D, Abramsky O, Reches A, Argov Z, Rabey JM, Chapman J, Rosenmann H, Gal A, Moshe Gomori J, Meiner V, Lossos A
J Neurol 2015 Oct;262(10):2346-51. Epub 2015 Jul 21 doi: 10.1007/s00415-015-7859-4. PMID: 26194201

Diagnosis

Koch RL, Soler-Alfonso C, Kiely BT, Asai A, Smith AL, Bali DS, Kang PB, Landstrom AP, Akman HO, Burrow TA, Orthmann-Murphy JL, Goldman DS, Pendyal S, El-Gharbawy AH, Austin SL, Case LE, Schiffmann R, Hirano M, Kishnani PS
Mol Genet Metab 2023 Mar;138(3):107525. Epub 2023 Jan 25 doi: 10.1016/j.ymgme.2023.107525. PMID: 36796138
Souza PVS, Badia BML, Farias IB, Pinto WBVR, Oliveira ASB, Akman HO, DiMauro S
J Inherit Metab Dis 2021 May;44(3):534-543. Epub 2020 Nov 13 doi: 10.1002/jimd.12325. PMID: 33141444
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065
Hellmann MA, Kakhlon O, Landau EH, Sadeh M, Giladi N, Schlesinger I, Kidron D, Abramsky O, Reches A, Argov Z, Rabey JM, Chapman J, Rosenmann H, Gal A, Moshe Gomori J, Meiner V, Lossos A
J Neurol 2015 Oct;262(10):2346-51. Epub 2015 Jul 21 doi: 10.1007/s00415-015-7859-4. PMID: 26194201

Therapy

Lau HA, Viskochil D, Tanpaiboon P, Lopez AG, Martins E, Taylor J, Malkus B, Zhang L, Jurecka A, Marsden D
Mol Genet Metab 2022 May;136(1):28-37. Epub 2022 Mar 9 doi: 10.1016/j.ymgme.2022.03.002. PMID: 35331634
Schiffmann R, Wallace ME, Rinaldi D, Ledoux I, Luton MP, Coleman S, Akman HO, Martin K, Hogrel JY, Blankenship D, Turner J, Mochel F
J Inherit Metab Dis 2018 Sep;41(5):877-883. Epub 2017 Nov 6 doi: 10.1007/s10545-017-0103-x. PMID: 29110179
Alvarez R, Casas J, López DJ, Ibarguren M, Suari-Rivera A, Terés S, Guardiola-Serrano F, Lossos A, Busquets X, Kakhlon O, Escribá PV
J Lipid Res 2017 Aug;58(8):1598-1612. Epub 2017 Jun 19 doi: 10.1194/jlr.M075531. PMID: 28630259Free PMC Article
Froese DS, Michaeli A, McCorvie TJ, Krojer T, Sasi M, Melaev E, Goldblum A, Zatsepin M, Lossos A, Álvarez R, Escribá PV, Minassian BA, von Delft F, Kakhlon O, Yue WW
Hum Mol Genet 2015 Oct 15;24(20):5667-76. Epub 2015 Jul 21 doi: 10.1093/hmg/ddv280. PMID: 26199317Free PMC Article
Roe CR, Bottiglieri T, Wallace M, Arning E, Martin A
Mol Genet Metab 2010 Oct-Nov;101(2-3):246-52. Epub 2010 Jul 6 doi: 10.1016/j.ymgme.2010.06.017. PMID: 20655781

Prognosis

Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065
Furtado LV, Kadri S, Wurst MN, Long BC, Segal JP, Pytel P
Muscle Nerve 2016 Mar;53(3):473-5. doi: 10.1002/mus.25017. PMID: 26670585
Trivedi JR, Wolfe GI, Nations SP, Burns DK, Bryan WW, Dewey RB Jr
Arch Neurol 2003 May;60(5):764-6. doi: 10.1001/archneur.60.5.764. PMID: 12756142
Klein CM, Bosch EP, Dyck PJ
Mayo Clin Proc 2000 Dec;75(12):1327-31. doi: 10.4065/75.12.1327. PMID: 11126844
Wierzba-Bobrowicz T, Stroińska-Kuś B
Folia Neuropathol 1994;32(1):37-41. PMID: 7922101

Clinical prediction guides

Gumber S, Connor-Stroud F, Howard D, Zhang X, Bradley BJ, Sherwood CC, Walker LC
Neuropathology 2023 Dec;43(6):463-471. Epub 2023 Apr 21 doi: 10.1111/neup.12906. PMID: 37086019Free PMC Article
Furtado LV, Kadri S, Wurst MN, Long BC, Segal JP, Pytel P
Muscle Nerve 2016 Mar;53(3):473-5. doi: 10.1002/mus.25017. PMID: 26670585
DiMauro S, Spiegel R
Acta Myol 2011 Oct;30(2):96-102. PMID: 22106711Free PMC Article
Trivedi JR, Wolfe GI, Nations SP, Burns DK, Bryan WW, Dewey RB Jr
Arch Neurol 2003 May;60(5):764-6. doi: 10.1001/archneur.60.5.764. PMID: 12756142
Wierzba-Bobrowicz T, Stroińska-Kuś B
Folia Neuropathol 1994;32(1):37-41. PMID: 7922101

Recent systematic reviews

Zebhauser PT, Cordts I, Hengel H, Haslinger B, Lingor P, Akman HO, Haack TB, Deschauer M
J Neurol 2022 Jun;269(6):2854-2861. Epub 2022 Jan 8 doi: 10.1007/s00415-022-10960-z. PMID: 34999962Free PMC Article

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