Lethal fetal and early neonatal presentation of adenylosuccinate lyase deficiency: observation of 6 patients in 4 families.
OBJECTIVE
To characterize a new lethal fetal and early postnatal variant of adenylosuccinate lyase (ADSL) deficiency.


METHODS
This was a retrospective analysis of 6 patients with very early presentation of ADSL deficiency.


RESULTS
Most of the 6 patients had impaired intrauterine growth, microcephaly, fetal hypokinesia, and a lack of fetal heart rate variability. Postnatally, they shared severe muscular hypotonia necessitating mechanical ventilation, intractable seizures, and early death. All 6 patients had biochemical evidence of severe (type 1) disease and low residual ADSL activities. All were compound heterozygous for mutations that, based on expression studies, have a pronounced effect on ADSL activity and/or stability.


CONCLUSIONS
ADSL deficiency may present with prenatal growth restriction, fetal and neonatal hypokinesia, and rapidly fatal neonatal encephalopathy. This clinical presentation is associated with genotypes resulting in very low residual enzyme activity.
Mouchegh
Katharina
K
Department of Pediatrics, Klinikum Neukölln, Berlin, Germany
Zikánová
Marie
M
Hoffmann
Georg F
GF
Kretzschmar
Benno
B
Kühn
Thomas
T
Mildenberger
Eva
E
Stoltenburg-Didinger
Gisela
G
Krijt
Jakub
J
Dvoráková
Lenka
L
Honzík
Tomás
T
Zeman
Jiri
J
Kmoch
Stanislav
S
Rossi
Rainer
R
D000264:Adenylosuccinate Lyase / Q000172:deficiency* / Q000235:genetics; D004247:DNA / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D005313:Fetal Death / Q000201:enzymology / Q000209:etiology*; D005500:Follow-Up Studies; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D011247:Pregnancy; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000150:complications / Q000201:enzymology* / Q000235:genetics; D012189:Retrospective Studies
D004247:DNA; D000264:Adenylosuccinate Lyase