title: Clinical, biochemical, neuropathological and molecular findings of the first Polish case of adenylosuccinase deficiency.
abstract: Adenylosuccinase (ADSL) deficiency is an autosomal recessive disorder affecting mainly the nervous system. The disease causes psychomotor retardation, frequently with autistic features and epilepsy. ADSL deficiency may be diagnosed by detection of two abnormal metabolites in body fluids--succinyladenosine (S-Ado) and succinylaminoimidazole carboxamide riboside (SAICAr). It is assumed that the former metabolite is neurotoxic. We present clinical, biochemical and neuropathological findings of a child affected by a severe form of ADSL deficiency. She had progressive neurological symptoms that started immediately after birth and died at 2.5 months of age. Macroscopically the brain showed signs of moderate atrophy. Histological examination of all grey matter structures showed widespread damage of neurons accompanied by microspongiosis of neuropile. Cerebral white matter showed lack of myelination in the centrum semiovale and diffuse spongiosis of neuropile. Myelination appropriate for the age was visible in posterior limb of internal capsule, in striatum, thalamus and in brain stem structures but diffuse destruction of myelin sheets was seen with severe marked astroglial reaction with signs of destruction of the cells and their processes. Ultrastructural examination showed enormous destruction of all cellular elements, but astonishingly mitochondria were relatively spared. The neuropathological changes can be considered as the neurotoxic result of metabolic disturbances connected with adenylosuccinase deficiency.
authors: Department of Metabolic Diseases, The Children's Memorial Health Institute, Polish Academy of Sciences, Warsaw, Poland. h.mierzewska@gmail.com
authors: Hanna
authors: H
authors: Mierzewska
authors: Bogna
authors: B
authors: Schmidt-Sidor
authors: Eliza
authors: E
authors: Lewandowska
authors: Wiesława
authors: W
authors: Grajkowska
authors: Katarzyna
authors: K
authors: Kuśmierska
authors: Elzbieta
authors: E
authors: Jurkiewicz
authors: Tomasz
authors: T
authors: Stepień
authors: Janina
authors: J
authors: Rafałowska
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid; D000264:Adenylosuccinate Lyase / Q000172:deficiency*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid; D001921:Brain / Q000648:ultrastructure*; D020739:Brain Diseases, Metabolic, Inborn / Q000134:cerebrospinal fluid / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D011044:Poland; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000134:cerebrospinal fluid / Q000473:pathology* / Q000503:physiopathology; D012263:Ribonucleosides / Q000134:cerebrospinal fluid
chemical_list: D012263:Ribonucleosides; C043566:succinylaminoimidazole carboxamide riboside; D000620:Aminoimidazole Carboxamide; C043565:succinyladenosine; D000264:Adenylosuccinate Lyase; D000241:Adenosine