Aspartyl glucosaminuria

from Wikipedia, the free encyclopedia
Classification according to ICD-10
E77.1 Defects in glycoprotein breakdown -

Aspartyl glucosaminuria

ICD-10 online (WHO version 2019)

The Aspartylglukosaminurie is a very rare congenital to the oligosaccharidoses associated lysosomal storage disease , mainly in Finland occurs with the main feature of a progressive reduction in intellectual capability.

Synonyms are: aspartyl glucosaminidase deficiency; English AGA deficiency; aspartylglucosamidase deficiency; Aspartyl glucosaminidase deficiency; glycosylasparaginase deficiency

distribution

The frequency is given as 1 in 18,500 people in Finland, inheritance is autosomal - recessive .

root cause

Of the disease are mutations in the AGA - gene on chromosome 4 locus q34.3 based encoding (1-aspartamide-β-N-acetylglucosamine amidohydrolase) for the N-Aspartylglukosaminidase. The enzyme defect leads to the accumulation of glycoasparagin ( storage disease ) in all tissues with increased excretion in the urine.

Clinical manifestations

Clinical criteria are:

  • Unremarkable development as a newborn, infant and toddler
  • First abnormalities at two to three years of age, mostly delayed language development, hyperkinesis and clumsiness
  • Mild mental retardation at first, then worsening until adolescence
  • Later almost complete loss of speech

In addition to facial dysmorphia , kyphoscoliosis , hernias , Cutis Laxa and increased airway infections and reduced height come. Hepatosplenomegaly , seizures , osteoporosis , hypermobility have also been described.

diagnosis

The x-ray shows irregular base and cover plates of the vertebral bodies and a thickened skullcap .

Asparty glycosamine, the activity of the enzyme aspartyl glucosamine hydrolase and the like increases in the urine . a. in lymphocytes , fibroblasts is decreased.

In magnetic resonance tomography , signal reductions in the thalamus and pulvinar , signal increases periventricular directly on the cortical ligament (juxtacortical) are visible.

history

It was first described in 1967 by the English doctors FA Jenner and RJ Pollitt. The designation was proposed in 1968 by the same working group.

therapy

The defective gene for the enzyme aspartyl glucosaminidase (AGA) is in the lysosomes. It is involved in the elimination of superfluous proteins. Without AGA, proteins accumulate, lead to malfunction of the lysosome and death of the cell. The lack of AGA activity can be partially remedied by chaperones, which enable the correct folding in defective proteins. The therapy is experimental, as the chaperones have so far only been approved for other ailments.

literature

  • T. Yamamoto, K. Shimojima, M. Matsufuji, R. Mashima, E. Sakai, T. Okuyama: Aspartylglucosaminuria caused by a novel homozygous mutation in the AGA gene was identified by an exome-first approach in a patient from Japan. In: Brain & development. Vol. 39, No. 5, May 2017, pp. 422-425, doi: 10.1016 / j.braindev.2016.12.004 , PMID 28063748 .
  • A. Kartal, K. Aydın: Brain MRI findings in two Turkish pediatric patients with aspartylglucosaminuria. In: The neuroradiology journal. Vol. 29, No. 5, October 2016, pp. 310-313, doi: 10.1177 / 1971400916665371 , PMID 27549151 , PMC 5033095 (free full text).
  • T. Opladen, F. Ebinger, J. Zschocke, D. Sengupta, T. Ben-Omran, N. Shahbeck, U. Moog, C. Fischer, F. Bürger, D. Haas, P. Ruef, I. Harting, H. Al-Rifai, GF Hoffmann: Aspartylglucosaminuria: unusual neonatal presentation in Qatari twins with a novel aspartylglucosaminidase gene mutation and 3 new cases in a Turkish family. In: Journal of child neurology. Vol. 29, No. 1, January 2014, pp. 36-42, doi: 10.1177 / 0883073812469049 , PMID 23271757 .

Individual evidence

  1. ↑ a b Bernfried Leiber (founder): The clinical syndromes. Syndromes, sequences and symptom complexes . Ed .: G. Burg, J. Kunze, D. Pongratz, PG Scheurlen, A. Schinzel, J. Spranger. 7., completely reworked. Edition. tape 2 : symptoms . Urban & Schwarzenberg, Munich et al. 1990, ISBN 3-541-01727-9 .
  2. ↑ a b Aspartylglucosaminuria. In: Orphanet (Rare Disease Database).
  3. ↑ a b c Genetics Home Reference
  4. ↑ Aspartylglucosaminuria.  In: Online Mendelian Inheritance in Man . (English)
  5. ↑ AM Tokola, LE Åberg, TH Autti: Brain MRI findings in aspartylglucosaminuria. In: Journal of neuroradiology. Journal de neuroradiology. Vol. 42, No. 6, December 2015, pp. 345-357, doi: 10.1016 / j.neurad.2015.03.003 , PMID 26026191 .
  6. ^ FA Jenner, RJ Pollitt: Large quantities of 2-acetamido-1- (beta-L-aspartamido) -1,2-dideoxyglucose in the urine of mentally retarded siblings. In: The Biochemical Journal Vol. 103: 48P-49P, 1967.
  7. ^ RJ Pollitt, FA Jenner, H. Merskey: Aspartylglycosaminuria . An inborn error of metabolism associated with mental defect. In: Lancet. Vol. 2, No. 7562, August 1968, pp. 253-255, PMID 4173687 .
  8. ↑ Antje Banning, Christina Gülec, Juha Rouvinen, Steven J. Gray & Ritva Tikkanen: Identification of Small Molecule Compounds for Pharmacological Chaperone Therapy of Aspartylglucosaminuria. Sci. Rep. 6, 37583; DOI: 10.1038 / srep37583 (2016)