A long-term survival case of arginase deficiency with severe multicystic white matter and compound mutations

Segawa, Yoshie; Matsufuji, Mayumi; Itokazu, Naoya; Utsunomiya, Hidetsuna; Watanabe, Yoriko; Yoshino, Makoto; Takashima, Sachio

doi:10.1016/j.braindev.2010.03.001

Cited by 16 publications

(15 citation statements)

References 7 publications

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“…Similar findings are recognized in most other UCDs in which hyperammonemia is a pathophysiologic factor (Blaser and Feigenbaum 2004). Multicystic encephalomalacia was described in a patient in her 30 s who, despite treatment, had persistently high plasma arginine levels (Segawa et al 2011).…”

Section: Clinical Characteristicssupporting

confidence: 74%

Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature

et al. 2015

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Hyperargininemia is caused by deficiency of arginase 1, which catalyzes the hydrolysis of L-arginine to urea as the final enzyme in the urea cycle. In contrast to other urea cycle defects, arginase 1 deficiency usually does not cause catastrophic neonatal hyperammonemia but rather presents with progressive neurological symptoms including seizures and spastic paraplegia in the first years of life and hepatic pathology, such as neonatal cholestasis, acute liver failure, or liver fibrosis. Some patients have developed hepatocellular carcinoma. A usually mild or moderate hyperammonemia may occur at any age. The pathogenesis of arginase I deficiency is yet not fully understood. However, the accumulation of L-arginine and the resulting abnormalities in the metabolism of guanidine compounds and nitric oxide have been proposed to play a major pathophysiological role. This article provides an update on the first patients ever described, gives an overview of the distinct clinical characteristics, biochemical as well as genetical background and discusses treatment options.

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Section: Clinical Characteristicssupporting

confidence: 74%

Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature

et al. 2015

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“…The neurological changes observed in typical ARG1 deficiency, without hyperammonemia, may be due to a significant increase in CSF arginine or CSF guanidino compounds [5, 7, 10, 15, 16]. Guanidino compounds are neurotoxic and can lead to seizures and demyelination [12, 17]. Our patient had elevations in creatine (2548 mmol/mol creatinine, 28–1700), α-N-acetylarginine (15.4 mmol/mol creatinine, 2–11.3), argininic acid (9.2 mmol/mol creatinine, 0.4–3.4), and γ-guanidinobutyric acid (17.1 mmol/mol creatinine, 1.7–7.9) (courtesy of Dr. Andreas Schulze).…”

Section: Discussionmentioning

confidence: 99%

“…Changes including ischemic changes of the depth of sulcus on T2 and diffusion weighted images, initial global or focal edema, basal ganglia involvement followed by myelin delay, ulegyria, and cystic lesions are recognised in most other UCDs in which hyperammonemia is a factor [22]. A case report of ARG1 deficiency with neonatal onset and hyperammonemia at 4 years of age revealed an end-stage brain with significant atrophy, cystic leukoencephalopathy with increased signal in the bilateral basal ganglia, thalami and hippocampal atrophy [12]. Our patient, who did have hyperammonemia, presented with findings at least as severe as those described in the other UCD disorders presenting with acute hyperammonemic crises in infancy.…”

Section: Discussionmentioning

confidence: 99%

“…Neonatal presentation of ARG1 deficiency with significant hyperammonemia is rare and only six case reports exist in the literature [7, 8, 9, 10, 11, 12]. In this report, we present an additional infant with ARG1 deficiency with hyperammonemia and compare the clinical and biochemical features of the proband and review the existing literature.…”

Section: Introductionmentioning

confidence: 96%

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Arginase I deficiency: Severe infantile presentation with hyperammonemia: More common than reported?

Jain-Ghai

Nagamani

Blasér

et al. 2011

Molecular Genetics and Metabolism

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Enzyme defects of the urea cycle typically present with significant hyperammonemia and its associated toxicity, in the first few months of life. However, arginase I (ARG1) deficiency, a rare autosomal recessive disorder, has classically been the exception. ARG1 deficiency usually presents later in life with spasticity, seizures, failure to thrive and developmental regression. Neonatal and early infantile presentation of ARG1 deficiency with severe hyperammonemia remains rare and only six such cases have been described We report a severely affected infant with ARG1 deficiency who presented at 6 weeks of age with lethargy, poor feeding and severe encephalopathy caused by hyperammonemia. The clinical and biochemical features of the proband and six other previously reported cases with neonatal or infantile-onset presentation of ARG1 deficiency with hyperammonemia are reviewed. In addition, the clinical spectrum of seven previously unpublished patients with later onset ARG1 deficiency, who also experienced recurrent hyperammonemia, is presented. Several biochemical abnormalities have been postulated to play a role in the pathogenesis of the neurological changes in ARG1 deficiency including hyperargininemia, elevated guanidino compounds and elevated glutamine levels, as well as the hyperammonemia. The index case demonstrated many of these. The cases reviewed here suggest a genotype/phenotype correlation and advocate for the addition of arginine as a primary target in newborn screening programs.

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“…Therefore, in DRD, there is likely a deficiency in dopamine, and related biogenic amines, throughout development. Age of onset is variable but often early, and symptoms range from focal to generalized dystonia to developmental delay (Segawa, 2011). Many of the symptoms are alleviated by l -DOPA administration, and LIDs are typically not a complication.…”

Section: Striosomes Signaling and Diseasementioning

confidence: 99%

Basal Ganglia Disorders Associated with Imbalances in the Striatal Striosome and Matrix Compartments

Crittenden¹,

Graybiel²

2011

Front. Neuroanat.

395

470

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The striatum is composed principally of GABAergic, medium spiny striatal projection neurons (MSNs) that can be categorized based on their gene expression, electrophysiological profiles, and input–output circuits. Major subdivisions of MSN populations include (1) those in ventromedial and dorsolateral striatal regions, (2) those giving rise to the direct and indirect pathways, and (3) those that lie in the striosome and matrix compartments. The first two classificatory schemes have enabled advances in understanding of how basal ganglia circuits contribute to disease. However, despite the large number of molecules that are differentially expressed in the striosomes or the extra-striosomal matrix, and the evidence that these compartments have different input–output connections, our understanding of how this compartmentalization contributes to striatal function is still not clear. A broad view is that the matrix contains the direct and indirect pathway MSNs that form parts of sensorimotor and associative circuits, whereas striosomes contain MSNs that receive input from parts of limbic cortex and project directly or indirectly to the dopamine-containing neurons of the substantia nigra, pars compacta. Striosomes are widely distributed within the striatum and are thought to exert global, as well as local, influences on striatal processing by exchanging information with the surrounding matrix, including through interneurons that send processes into both compartments. It has been suggested that striosomes exert and maintain limbic control over behaviors driven by surrounding sensorimotor and associative parts of the striatal matrix. Consistent with this possibility, imbalances between striosome and matrix functions have been reported in relation to neurological disorders, including Huntington’s disease, L-DOPA-induced dyskinesias, dystonia, and drug addiction. Here, we consider how signaling imbalances between the striosomes and matrix might relate to symptomatology in these disorders.

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A long-term survival case of arginase deficiency with severe multicystic white matter and compound mutations

Cited by 16 publications

References 7 publications

Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature

Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature

Arginase I deficiency: Severe infantile presentation with hyperammonemia: More common than reported?

Basal Ganglia Disorders Associated with Imbalances in the Striatal Striosome and Matrix Compartments

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