Objective: The purpose of this case report is to detail the phenotype of parkinsonism encountered in a patient with Argininosuccinate Lyase Deficiency (ASLD) that has never been previously reported.

Background: ASLD is a rare metabolic disorder of the urea cycle, resulting in decreased conversion of argininosuccinate into fumarate and arginine, causing argininosuccinic aciduria and low arginine levels. Movement disorders, mostly dystonia, have been previously reported in ASLD, but parkinsonism has not been reported.

Methods: Case report: pubmed literature search for argininosuccinate lyase deficiency, ASLD, urea cycle disorder, parkinsons, parkinsonism, movement disorder, dystonia, microdeletion, PRODH, DGCR2, 22q11.2

Results: A 61-year-old female with no significant family history and previously unknown cause of moderate intellectual disability was evaluated for tremors and falls and diagnosed with new onset parkinsonism. On examination dysmorphic facial features were appreciated with high forehead, dolichocephaly, high arched palate and short 5th metacarpals. Neurological examination showed mild symmetric mixed rest and action tremor present in all four extremities, rigidity, mild bradykinesia and postural instability. Also noticeable were cerebellar ataxia signs, upper motor neuron signs, frontal release signs and severe oculomotor impersistence with apraxia. Brain MRI revealed mild volume loss and mild  chronic small vessel disease. Workup revealed markedly elevated urine argininosuccinic acid levels with normal ammonia level. Serum and urine proline levels were normal. Microarray showed an incidental finding of heterozygous 108 kb deletion at chromosome 22q11.21 involving PRODH (Proline dehydrogenase) and DGCR2 (DiGeorge syndrome critical region 2). No association with parkinsonism has been reported with these genes. A diagnosis of ASLD was made after complete work up by the metabolic expert and was started on treatment.

Conclusions: Urea cycle disorders (UCDs) such as ASLD can have prominent neurocognitive manifestations. Symptoms appear to be unrelated to the severity or duration of hyperammonemia episodes, unlike other UCDs, suggesting an alternative mechanism of neuronal insult. This patient’s symptoms appear to be unrelated to her incidental microdeletions in PRODH and DGCR2. Our case is the first reported phenotype of Parkinsonism in patient with ASLD and hopefully will be useful to future studies in this area

References: Kölker, S., Valayannopoulos, V., Burlina, A. B., Sykut-Cegielska, J., Wijburg, F., Teles, E., Arnoux, J. (2015, April). The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2: the evolving clinical phenotype. Journal of Inherited Metabolic Disease.

Gropman, A., Summar, M., & Leonard, J. (2007, November). Neurological implications of urea cycle disorders. Journal of Inherited Metabolic Diseases, 30(6), 865-879.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/first-reported-case-of-parkinsonism-in-a-patient-with-argininosuccinate-lyase-deficiency/