Early‐onset hyperargininaemia: A severe disorder?

Schiff, Manuel; Benoist, Jean‐François; Cardoso, Maria Luı́s; Elmaleh‐Bergès, Monique; Forey, Pierre-Louis; Santiago, João Gonçalo; Baulny, Hélène Ogier de

doi:10.1007/s10545-009-1137-5

Cited by 12 publications

(10 citation statements)

References 12 publications

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“…It presents as a progressive neurologic impairment with spasticity during childhood. ALF has been described in some acute-onset cases, with normalization under treatment (Schiff et al 2009), as well as hepatomegaly (Cederbaum et al 1979;Crombez and Cederbaum 2005) and severe neonatal cholestasis (Scaglia and Lee 2006). Hepatomegaly with fatty liver (Jordá et al 1986) and coagulopathy, cirrhosis complicated with portal hypertension, ESLD, and HCC complicating cirrhosis in a 22-year-old woman (Tsang et al 2012) have been described and can occur without encephalopathy (Braga et al 1997;Scaglia et al 2004;Edwards et al 2009;T s a n ge ta l2012).…”

Section: Arginase Deficiency (Argd; Omim 207800)mentioning

confidence: 99%

Liver involvement in urea cycle disorders: a review of the literature

Bigot¹,

Tchan²,

Thoreau³

et al. 2017

J of Inher Metab Disea

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Urea cycle disorders (UCDs) are inborn errors of metabolism of the nitrogen detoxification pathway and encompass six principal enzymatic deficiencies. The aging of UCD patients leads to a better knowledge of the long-term natural history of the condition and to the reporting of previously unnoticed manifestations. Despite historical evidence of liver involvement in UCDs, little attention has been paid to this organ until recently. Hence, we reviewed the available scientific evidence on acute and chronic liver dysfunction and liver carcinogenesis in UCDs and discuss their pathophysiology. Overall, liver involvement, such as acute liver failure or steatotic-like disease, which may evolve toward cirrhosis, has been reported in all six main UCDs. Excessive glycogen storage is also a prominent histologic feature, and hypoglycemia has been reported in citrin deficiency. Hepatocarcinomas seem frequent in some UCDs, such as in citrin deficiency, and can sometimes occur in non-cirrhotic patients. UCDs may differ in liver involvement according to the enzymatic deficiency. Ornithine transcarbamylase deficiency may be associated more with acute liver failure and argininosuccinic aciduria with chronic liver failure and cirrhosis. Direct toxicity of metabolites, downstream metabolic deficiencies, impaired tricarboxylic acid cycle, oxidative stress, mitochondrial dysfunction, energy deficit, and putative toxicity of therapies combine in various ways to cause the different liver diseases reported.

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Section: Arginase Deficiency (Argd; Omim 207800)mentioning

confidence: 99%

Liver involvement in urea cycle disorders: a review of the literature

Bigot¹,

Tchan²,

Thoreau³

et al. 2017

J of Inher Metab Disea

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“…Symptoms in the neonatal period include hepatomegaly, neonatal cholestasis, and liver failure but also drowsiness, seizures and cerebral edema with mild or moderate elevations of ammonia of up to 250 µmol/l (Jorda et al 1986;Picker et al 2003;Braga et al 1997;Schiff et al 2009). Interestingly, there are no reports of cases of severe hyperammonemia in the first days of life as typically seen in other urea cycle disorders.…”

Section: Clinical Characteristicsmentioning

confidence: 99%

“…Magnetic resonance imaging (MRI) studies have shown variable cerebral and less often cerebellar atrophy (Gungor et al 2008;Carvalho et al 2012b;Schiff et al 2009), ischemic changes and edema, signal changes in the posterior putamina and insular cortex (Gungor et al 2008), and abnormal myelination (Brockstedt et al 1990). Similar findings are recognized in most other UCDs in which hyperammonemia is a pathophysiologic factor (Blaser and Feigenbaum 2004).…”

Section: Clinical Characteristicsmentioning

confidence: 99%

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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“…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: 97%

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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Early‐onset hyperargininaemia: A severe disorder?

Abstract: Early identification and management of this rare but potentially treatable affection is crucial as delayed management may result in poor neurological outcome.

Cited by 12 publications

References 12 publications

Liver involvement in urea cycle disorders: a review of the literature

Liver involvement in urea cycle disorders: 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?

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