A new case of arginase deficiency in a Spanish male

Jordá, A.; Rubio, Vicente; Portolés, Manuel; Vilas, José María Tarazona; García-Piño, J

doi:10.1007/bf01800491

Cited by 27 publications

(18 citation statements)

References 8 publications

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“…Samples were collected from each of the living, published cases. Their clinical and biochemical descriptions have been reported earlier (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Eight unpublished cases were included as well: two cases of Dr.…”

Section: Methodsmentioning

confidence: 96%

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Guanidino Compound Analysis as a Complementary Diagnostic Parameter for Hyperargininemia: Follow-Up of Guanidino Compound Levels during Therapy

et al. 1990

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ABSTRACT. The aim of this collaborative study was to normalized by therapy, the levels of the catabolites of investigate whether guanidino compound analyses in the arginine are still elevated. (Pediatr Res 27: 297-303,1990) biologic fluids can be used as a complementary diagnostic parameter for hyperargininemia. Guanidino compounds were determined in the biologic fluids of all known living hyperargininemic patients using a cation exchange chromatographic system with a fluorescence detection method. The serum arginine, homoarginine, a-keto-6-guanidinoDeficiency of arginase, the last enzyme of the urea cycle, leads valeric acid, argininic acid, and N-a-acetylarginine levels to hyperargininemia. The first clinical and biochemical descripof all the hyperargininemic patients are higher than the tions of two sisters affected with hyperargininemia were pubnormal range. Similar increases were seen for the urinary lished in 1969 (1) and 1970 (2, 3). Five y later, another sister was excretion of a-keto-6-guanidinovaleric acid and argininic diagnosed shortly after birth (4). Since then, 19 other cases from acid. Untreated hyperargininemic patients have the highest 17 families have been reported (5-22). Patients with hyperargiguanidino compound levels in cerebrospinal fluid. How-ninemia present a neuropsychiatric syndrome consisting of varyever, even under therapy, the arginine, homoarginine, a-ing degrees of mental retardation, epilepsy, and progressive spasketo-6-guanidinovaleric acid, and argininic acid levels in ticity. This latter symptom is at variance with other defects of cerebrospinal fluid are still increased. Protein restriction the urea cycle. Some patients have, in addition, recurrent epialone is not sufficient to normalize the hyperargininemia, sodes of vomiting and irritability accompanied by moderate but protein restriction together with supplementation of hyperammonemia. As a consequence of the arginase deficiency, essential amino acids with or without sodium benzoate the patients accumulate excessive arginine. Some secondary cadecreases further the arginine levels. However, whereas tabolites of arginine, guanidino compounds, are massively exthe argininemia can be normalized, the catabolites of ar-creted in the urine of these patients (23). Figure 1 shows some ginine are still increased. We conclude that the urinary proposed catabolic pathways of arginine in patients with hyperamino acid levels may remain normal in hyperargininemia, argininemia. whereas consistent increases of the guanidino compounds In hyperargininemia it is unclear whether ammonia is the are observed. Thus, guanidino compound analyses can be principal toxin. Indeed, the presence of normal or only slightly used as a complementary biochemical diagnostic parameter elevated ammonia levels has been demonstrated in several pafor hyperargininemia. Although the argininemia can be tients (6,7,9,15), and the progressive spasticity typically en-

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Section: Methodsmentioning

confidence: 96%

“…Twenty-two cases have been published. The patients described by Jorda et al (19), Endres et al (16), and Sakiyama et al (12) have died. No biologic fluids from these patients were available for this study.…”

Section: Methodsmentioning

confidence: 97%

Guanidino Compound Analysis as a Complementary Diagnostic Parameter for Hyperargininemia: Follow-Up of Guanidino Compound Levels during Therapy

et al. 1990

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“…Hepatomegaly can be present, especially during hyperammonemic crises (Jorda et al 1986;Braga et al 1997;Edwards et al 2009; Scaglia and Lee 2006). Mild hepatic dysfunction with transient elevation of liver transaminases and coagulation abnormalities during catabolic episodes has been observed in a few patients with an otherwise typical neurological picture, and cases of persistent coagulopathy have been reported ( Scaglia and Lee 2006;Crombez and Cederbaum 2005;Brusilow 2001;Carvalho et al 2012b).…”

Section: Clinical Characteristicsmentioning

confidence: 96%

“…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: 98%

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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“…ARG1D markedly differs from other UCDs in that it rarely manifests in the neonatal period [216-218], causing progressive spastic paraplegia and developmental delay between 2 and 4 years of age, with hepatomegaly and in some cases with hyperammonemic episodes [21] although metabolic decompensations are rarer than in other UCDs [21,219]. The increased plasma arginine level is the disease hallmark, but this increase may be small [220], rendering highly desirable the confirmation of the diagnosis by enzymatic assays easily carried out in erythrocytes [76] or by genetic analysis [219,221].…”

Section: Recommendations For Specific Disordersmentioning

confidence: 99%

Suggested guidelines for the diagnosis and management of urea cycle disorders

Häberle

Boddaert

Burlina

et al. 2012

Orphanet J Rare Dis

511

623

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Urea cycle disorders (UCDs) are inborn errors of ammonia detoxification/arginine synthesis due to defects affecting the catalysts of the Krebs-Henseleit cycle (five core enzymes, one activating enzyme and one mitochondrial ornithine/citrulline antiporter) with an estimated incidence of 1:8.000. Patients present with hyperammonemia either shortly after birth (~50%) or, later at any age, leading to death or to severe neurological handicap in many survivors. Despite the existence of effective therapy with alternative pathway therapy and liver transplantation, outcomes remain poor. This may be related to underrecognition and delayed diagnosis due to the nonspecific clinical presentation and insufficient awareness of health care professionals because of disease rarity. These guidelines aim at providing a trans-European consensus to: guide practitioners, set standards of care and help awareness campaigns. To achieve these goals, the guidelines were developed using a Delphi methodology, by having professionals on UCDs across seven European countries to gather all the existing evidence, score it according to the SIGN evidence level system and draw a series of statements supported by an associated level of evidence. The guidelines were revised by external specialist consultants, unrelated authorities in the field of UCDs and practicing pediatricians in training. Although the evidence degree did hardly ever exceed level C (evidence from non-analytical studies like case reports and series), it was sufficient to guide practice on both acute and chronic presentations, address diagnosis, management, monitoring, outcomes, and psychosocial and ethical issues. Also, it identified knowledge voids that must be filled by future research. We believe these guidelines will help to: harmonise practice, set common standards and spread good practices with a positive impact on the outcomes of UCD patients.

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A new case of arginase deficiency in a Spanish male

Cited by 27 publications

References 8 publications

Guanidino Compound Analysis as a Complementary Diagnostic Parameter for Hyperargininemia: Follow-Up of Guanidino Compound Levels during Therapy

Guanidino Compound Analysis as a Complementary Diagnostic Parameter for Hyperargininemia: Follow-Up of Guanidino Compound Levels during Therapy

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

Suggested guidelines for the diagnosis and management of urea cycle disorders

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