Elsevier

Pediatric Neurology

Volume 16, Issue 3, April 1997, Pages 252-255
Pediatric Neurology

Case report
First U.S. case of adenylosuccinate lyase deficiency with severe hypotonia,☆☆

https://doi.org/10.1016/S0887-8994(97)89979-1Get rights and content

Abstract

Adenylosuccinate lyase (ASL) deficiency is a defect in purine de novo synthesis pathway. The disease has variable clinical presentation involving psychomotor retardation, seizures, hypotonia, and autism. The presence of succinyladenosine and succinylamino-imidazole carboxamide riboside (SAICA riboside) in body fluids characterizes the biochemical phenotype. All cases of ASL deficiency described to date have been diagnosed in Europe. Using a high-resolution thin-layer chromatography (TLC) technique combining screening for ASL deficiency and disorders of saccharide metabolism, we found the first case of this disease in the US. The patient presented with delayed motor development and profound hypotonia. The family history and routine laboratory tests were negative. Screening for metabolic disorders detected the presence of succinyladenosine and SAICA riboside in urine. The activity of ASL in the patient's skin fibroblasts was 43% of controls (patient, mean = 1.20 nmol/ min/mg of protein, s = 0.21, n = 3; controls, mean = 2.78 nmol/min/mg of protein, s = 0.61, n = 7). In a 15-month-old girl with profound hypotonia, we established the diagnosis of ASL deficiency by demonstrating succinyladenosine and SAICA riboside in urine and decreased residual activity of ASL in skin fibroblasts.

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    In particular, the fatal neonatal form typically exhibits a succinyladenosine:SAICAR ratio of <1, compared with a ratio of ∼1.0 in the severe type presenting in early infancy with severe developmental problems (such as those described in case 2) [6-10]. Succinyladenosine:SAICAR ratios of ≥2 are usually found in moderate or mild phenotypes presenting in the first few years of childhood (as illustrated by case 3) [10-13]. More than 40 mutations associated with ADSL mutations have been reported to date, all of them missense mutations, including the recurrent c.1279G>A (p.Arg426His) substitution, associated with a most severe encephalopathic form of the disease in the homozygous state [13].

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Presented in part in abstract form at the 33rd SSIEM annual symposium, Cardiff, Wales 1996, and published in abstract form in J Inherit Metab Dis 1996;19(suppl. 1):A22.

☆☆

This work was supported in part by Mayo Foundation and by Project No. IGA MZCR 1831-2. Until December 1995, 3800 specimens were analyzed by high-resolution TLC at Mayo Clinic, Rochester, MN, and 800 were analyzed at J. Gregor Mendel Children's Hospital, Brno, The Czech Republic. Three urine specimens from ASL-deficient patients were provided by Dr. Jakub Krijt, Center for Hereditary Metabolic Disorders, Prague, The Czech Republic (known cases 2–4, 4a, 4b are two different specimens from the same patient); one was provided by Dr. Georges van den Berghe, International Institute of Cellular and Molecular Pathology, Brussels, Belgium (known case 1).

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