Succinat-Semialdehyd-Dehydrogenase-Mangel: eine vererbbare neurometabolische Erkrankung

M. Gahr; B. J. Connemann; C. J. Schönfeldt-Lecuona; R. W. Freudenmann

doi:10.1055/s-0032-1330544

Fortschritte der Neurologie · Psychiatrie, Table of Contents

Fortschr Neurol Psychiatr 2013; 81(3): 154-161
DOI: 10.1055/s-0032-1330544

Übersicht

Succinat-Semialdehyd-Dehydrogenase-Mangel: eine vererbbare neurometabolische Erkrankung

Succinic Semialdehyde Dehydrogenase Deficiency: An Inheritable Neurometabolic Disease

M. Gahr

,

B. J. Connemann

,

C. J. Schönfeldt-Lecuona

,

R. W. Freudenmann

Abstract

Zusammenfassung

Succinat-Semialdehyd-Dehydrogenase-Mangel (SSADHD) ist eine neurometabolische Erkrankung mit autosomal-rezessivem Erbgang. Gegenwärtig sind weltweit zwar nur ca. 450 Fälle bekannt, dennoch gehört der SSADHD zu den häufigen pädiatrisch relevanten Störungen des Neurotransmitterstoffwechsels. SSADHD liegt eine Mutation im Aldh5a1-Gen zugrunde, was zu einer gestörten Funktion der Succinat-Semialdehyd-Dehydrogenase führt. Dadurch kommt es zu einer Akkumulation von γ-Aminobuttersäure und Succinat-Semialdehyd, welches bei SSADHD alternativ mittels der Succinat-Semialdehyd-Reduktase zu γ-Hydroxy-Buttersäure metabolisiert wird. Der klinische Phänotyp ist unspezifisch mit ausgeprägter interindividueller Varianz. Motorische und sprachliche Entwicklungsverzögerung sowie Epilepsie, Intelligenzminderung, Schlafstörung, Ataxie, muskuläre Hypotonie und Verhaltensauffälligkeiten sind jedoch häufig. Erste Symptome treten häufig bereits im ersten Lebensjahr auf, während die Erkrankung insgesamt eher statisch verläuft. Gegenwärtig existieren keine kausalen Therapieoptionen.

Abstract

Succinic semialdehyde dehydrognase deficiency (SSADHD) is a neurometabolic disease with autosomal recessive inheritance. Although only about 450 cases are known worldwide, SSADHD is a frequent paediatric disorder of the neurotransmitter metabolism. SSADHD is caused by a mutation of the Aldh5a1-gene resulting in a dysfunction of the enzyme succinic semialdehyde dehydrogenase. This is followed by an accumulation of γ-aminobutyric acid and succinic semialdehyde that is alternatively metabolised via succinic semialdehyde reductase to γ-hydroxybutyric acid. The clinical phenotype is unspecific with pronounced interindividual variability. However, delayed acquisition of motor and language developmental milestones as well as epilepsy, mental retardation, sleep disorder, ataxia, muscle hypotonia, and behavioural disturbances are frequent. First symptoms frequently occur in the first year of life while the general course of the disease is non-progressive. Currently, no causal therapy exists.

Schlüsselwörter

Autismus - GABA - GHB - Neurotransmitter - 4-Hydroxy-Buttersäure-Azidurie

Key words

autism - GABA - GHB - neurotransmitter - 4-hydroxybutyric aciduria

Full Text

References

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