Hereditary diffuse leukoencephalopathy with axonal spheroids

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Classification according to ICD-10
E75.2 Other sphingolipidoses
ICD-10 online (WHO version 2019)

The Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a very rare, typically beginning in adulthood, to the group of Sphingolipidoses and leukodystrophies be counted congenital disease of the central nervous system with the features of a progressive movement disorder (especially gait disturbance ) and a mental impairment .

HDLS, together with another rare disease, POLD (Pigmentary Orthochromatic Leukodystrophy), is grouped under the generic term Leukodystrophy with axonal spheroids and pigmented glia ( ALSP, Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia ).

Synonyms are: ALSP (adult leukoencephalopathy with axonal spheroids and pigmented glia); Familial dementia type Neumann; FPSG (Familial Progressive Subcortical Gliosis); GPSC; HDLS (Hereditary diffuse leukoencephalopathy with spheroids); Orthochromatic pigmented leukodystrophy; Autosomal dominant leukoencephalopathy with neuroaxonal spheroids; POLD; Subcortical Gliosis Neumann

distribution

The frequency is given as less than 1 in 1,000,000, inheritance is autosomal dominant .

root cause

Of the disease are often sporadic mutations in either the CSF1R - gene at locus 5q32 based or AARS2 gene with then autosomal recessive inheritance.

There are also cases of HDLS in which no gene has yet been identified.

The mechanism by which the disease occurs when these mutations are present is so far unknown, but the subject of current research.

Clinical manifestations

Diagnosis

The diagnosis is based on the clinical picture and the findings from MR imaging : Indicative findings are increasing leukoencephalopathy in the frontal lobe together with cerebral atrophy .

The diagnosis can be confirmed human genetically or histologically by means of a brain biopsy . Typical for the histological picture are pronounced myelin loss , axonal spheroids and pigmented macrophages .

Differential diagnosis

The list of clinically similar diseases is extensive, and imaging is not specific either.

therapy

A causal treatment is not yet known and is aimed at the symptoms with physiotherapy , speech therapy and occupational therapy . In addition, drugs can be used against spasticity and rigidity . Since the disease is very rare and therefore little known, patients are usually cared for in centers for rare diseases (ZSE) , such as the ZSE at the University Clinic Tübingen.

forecast

The average survival time is six years, and the cause of death is usually a consequence of movement disorders such as pneumonia and malnutrition .

history

The first description was in 1984 by the Swede R. Axelsson and colleagues.

Individual evidence

  1. ^ A b R. Axelsson, M. Röyttä, P. Sourander, HO Akesson, O. Andersen: Hereditary diffuse leucoencephalopathy with spheroids. In: Acta psychiatrica Scandinavica. Supplement. Volume 314, 1984, pp. 1-65, PMID 6595937 .
  2. ↑ a b Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia. In: Orphanet (Rare Disease Database).
  3. ↑ Leukoencephalopathy, diffuse hereditary, with spheroids.  In: Online Mendelian Inheritance in Man . (English)
  4. ↑ a b c R. Rademakers, M. Baker, AM Nicholson, NJ Rutherford, N. Finch, A. Soto-Ortolaza, J. Lash, C. Wider, A. Wojtas, M. DeJesus-Hernandez, J. Adamson, N. Kouri, C. Sundal, EA Shuster, J. Aasly, J. MacKenzie, S. Roeber, HA Kretzschmar, BF Boeve, DS Knopman, RC Petersen, NJ Cairns, B. Ghetti, S. Spina, J. Garbern, AC Tselis, R. Uitti, P. Das, JA Van Gerpen, JF Meschia, S. Levy, DF Broderick, N. Graff-Radford, OA Ross, BB Miller, RH Swerdlow, DW Dickson, ZK Wszolek: Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. In: Nature genetics. Volume 44, number 2, December 2011, pp. 200-205, doi: 10.1038 / ng.1027 , PMID 22197934 , PMC 3267847 (free full text).
  5. ↑ a b DS Lynch, WJ Zhang, R. Lakshmanan, JA Kinsella, GA Uzun, M. Karbay, Z. Tüfekçioglu, H. Hanagasi, G. Burke, N. Foulds, SR Hammans, A. Bhattacharjee, H. Wilson, M. Adams, M. Walker, JA Nicoll, J. Chataway, N. Fox, I. Davagnanam, R. Phadke, H. Houlden: Analysis of Mutations in AARS2 in a Series of CSF1R-Negative Patients With Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia. In: JAMA neurology. [Electronic publication before printing] October 2016, doi: 10.1001 / jamaneurol.2016.2229 , PMID 27749956 .
  6. ↑ a b medizin.uni-tuebingen.de
  7. ↑ a b C. Sundal, J. Lash, J. Aasly, S. Øygarden, S. Roeber, H. Kretzschman, JY Garbern, A. Tselis, R. Rademakers, DW Dickson, D. Broderick, ZK Wszolek: Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS): a misdiagnosed disease entity. In: Journal of the neurological sciences. Volume 314, number 1–2, March 2012, pp. 130–137, doi: 10.1016 / j.jns.2011.10.006 , PMID 22050953 , PMC 3275663 (free full text).
  8. ↑ B. Bender, U. Klose, T. Lindig, S. Biskup, T. Nägele, L. Schöls, KN ​​Karle: Imaging features in conventional MRI, spectroscopy and diffusion weighted images of hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS). In: Journal of neurology. Volume 261, Number 12, December 2014, pp. 2351-2359, doi: 10.1007 / s00415-014-7509-2 , PMID 25239393 .
  9. ^ R. Axelsson, M. Röyttä, P. Sourander, HO Akesson, O. Andersen: Hereditary diffuse leucoencephalopathy with spheroids. In: Acta psychiatrica Scandinavica. Supplement. Volume 314, 1984, pp. 1-65, PMID 6595937 .

literature