{ "@context": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/context/doc", "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051", "id": "CG-AC:AC1051", "type": "ClinicalActionabilityReport", "metadata": { "schemaLabel": "AC-Sepio.Beta-1 (Unofficial)", "contentVersionId": "30433", "producedAtUTC": "Thu, 10 Sep 2026 20:44:32 -0000", "note": "DISCLAIMER: The SEPIO-inspired schema presented here is an initial prototype for Clinical Actionability curation summaries and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema." }, "description": "JSON-LD representation of ClinGen Actionability Stage 2 report modeled with SEPIO. The hierarchically structured document will include:\n1. Contextual & topic information, such as the **conditions/diseases** and the **genes**.\n2. Categorized **evidence narratives**, with references.\n\t* This content corresponds to the texts within the *Actionability Summary Report*\n4. **Outcome & Intervention** pairs, with **consensus scoring** in 5 dimensions:\n\t1. Outcome Severity\n\t2. Outcome Likelihood\n\t3. Intervention Effectiveness\n\t4. Nature of the Intervention\n\t5. Total (Overall) Score\n\n*( Note: The summary report does not include the **Screening Survey** which led to preparation of the actionability report. )", "condition": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/co", "id": "CG-AC:AC1051/co", "type": "GeneticCondition", "label": "Hyperargininemia", "description": "Arginase deficiency is a rare autosomal recessive amino acid metabolism disorder characterized clinically by variable degrees of hyperammonemia, developing from about 3 years of age, and leading to progressive loss of developmental milestones and spasticity in the absence of treatment. The condition is also known as ARG1 Deficiency, Arginase-1 Deficiency, and Arginase deficiency." }, "outcome": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/ou/Morbidity%20due%20to%20hyperargininemia", "id": "CG-AC:AC1051/ou/Morbidity due to hyperargininemia", "type": "Outcome", "label": "Morbidity due to hyperargininemia" } ], "intervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/intv/Surveillance%20by%20specialists%20to%20guide%20management%2C%20including%20diet%2C%20supplements%2C%20nitrogen%20scavengers%2C%20and%20emergency%20planning", "id": "CG-AC:AC1051/intv/Surveillance by specialists to guide management, including diet, supplements, nitrogen scavengers, and emergency planning", "type": "Intervention", "label": "Surveillance by specialists to guide management, including diet, supplements, nitrogen scavengers, and emergency planning" } ], "clinicalActionabilityProfile": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/cap", "id": "CG-AC:AC1051/cap", "type": "Assertion", "assertionMethod": "The ClinGen AWG developed a standardized protocol to generate evidence-based profiles of clinical actionability of genes and associated disorders in the form of summary reports and semiquantitative metric (SQM) scores.", "releaseDate": "Tue, 22 Apr 2025 00:00:00 -0000", "releaseNum": "1.0.0", "media": "call" }, "evidenceStatements": { "evidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/en/cf", "id": "CG-AC:AC1051/en/cf", "type": "EvidenceNarrative", "narrative": "Arginase deficiency markedly differs from other UCDs because patients rarely present in the neonatal period (rarely neonatal cholestatic jaundice has been reported). Between 1 and 4 years of age, progressive spastic paraplegia (specific to arginase deficiency) and developmental delay evolve, with hepatomegaly and in some patients, hyperammonemic episodes. Additional clinical features of arginase deficiency can include growth deficiency, microcephaly (can be congenital), feeding issues requiring supplemental feeding tube, severe spasticity, and seizures. Hepatic dysfunction, if present, is usually mild, though, some adults develop hepatocellular carcinoma. Individuals can also develop tremor, ataxia, and choreoathetosis. Episodic hyperammonemia of variable degree is infrequently severe enough to be life threatening or to cause death. This decompensation is often triggered by febrile illness, particularly diarrhea and vomiting, fasting and any protein loading but an obvious precipitating cause is not always apparent. Early signs of decompensation may be subtle, lethargy, loss of appetite or and altered mental status but in some cases is asymptomatic and only recognized if blood ammonia is obtained during an acute illness. Signs of decompensation may be difficult to assess such as just “not right.” Older individuals may present with postoperative encephalopathy. Overall, metabolic decompensations are rarer in ARGD1 than in other UCDs.", "evidenceDomainTag": "Nature of the Threat.Clinical Features", "publication": [ "CG-AC:RF003862", "CG-AC:RF000503", "CG-AC:RF003287", "CG-AC:RF003865", "CG-AC:RF003866" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/en/nh", "id": "CG-AC:AC1051/en/nh", "type": "EvidenceNarrative", "narrative": "Individuals treated from birth, either by newborn screening (NBS) or having an affected older sibling, appear to have minimal symptoms.\n\nUntreated individuals have slowing of linear growth at age one to three years, followed by development of spasticity, plateauing of cognitive development, and subsequent loss of developmental milestones. Developmental delays have been the earliest reported observed manifestations (mean 2.7 years), followed by intellectual disability (mean 3.6 years), seizures (mean 4.6 years), and motor deficits (mean 4.8 years). If untreated, arginase deficiency usually progresses to severe spasticity, loss of ambulation, complete loss of bowel and bladder control, and severe intellectual disability. Full scale IQ in adults is in the 70s, and about half are able to live independently, though they experience significant memory and fine motor deficits. Mildly affected individuals and those treated early in life may be able to hold a job.", "evidenceDomainTag": "Nature of the Threat.Natural History", "publication": [ "CG-AC:RF003862", "CG-AC:RF000503", "CG-AC:RF003865" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/en/potgd", "id": "CG-AC:AC1051/en/potgd", "type": "EvidenceNarrative", "narrative": "Arginase deficiency is one of the rarest urea cycle defects (UCD). Arginase deficiency is estimated to account for approximately 3.5% of all UCD cases. To date, more than 260 individuals with arginase deficiency have been identified. The incidence of arginase deficiency has been estimated at between 1:350,000 and 1:1,000,000.", "evidenceDomainTag": "Nature of the Threat.Prevalence of the Genetic Disorder", "publication": [ "CG-AC:RF003862", "CG-AC:RF003863", "CG-AC:RF000503", "CG-AC:RF003864", "CG-AC:RF003408" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/en/ACMI2856", "id": "CG-AC:AC1051/en/ACMI2856", "type": "EvidenceNarrative", "narrative": "Autosomal Recessive", "evidenceDomainTag": "Threat Materialization Chances.Modes of Inheritance", "publication": [ "CG-AC:RF003862", "CG-AC:RF003863", "CG-AC:RF003408", "CG-AC:RF003870" ] } ], "tieredEvidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/ten/NOI3052", "id": "CG-AC:AC1051/ten/NOI3052", "type": "TieredEvidenceNarrative", "narrative": "Identified interventions include dietary therapy, medications, and avoidance of possible triggers (e.g., medications). Additionally, individuals with UCDs require lifelong monitoring. Long-term treatment is challenging for individuals and families because of the poor palatability (particularly of essential amino acids), the volume and frequency of diet and drug administrations. Nasogastric tube or gastrostomy feeding may be necessary to ensure sufficient energy and/or protein intake.", "evidenceDomainTag": "Acceptability of Intervention.Natures of Intervention", "publication": [ "CG-AC:RF003287" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/ten/CDEC3120", "id": "CG-AC:AC1051/ten/CDEC3120", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "Arginase deficiency may be misdiagnosed as static spastic diplegia (cerebral palsy).", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF003862", "CG-AC:RF000501" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/ten/CDEC3119", "id": "CG-AC:AC1051/ten/CDEC3119", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "Arginase deficiency is currently a secondary condition on the Recommended Uniform Screening Panel. Not all states in the US screen for and detect newborns with arginase deficiency. Symptomatic individuals may present with atypical findings or have untreated arginase deficiency (resulting from NBS not performed or false negative NBS result).", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF003862" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/ten/CDEC3118", "id": "CG-AC:AC1051/ten/CDEC3118", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "The most common misdiagnosis of early onset UCD patients is neonatal sepsis.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF003862", "CG-AC:RF000501" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/ten/ACPE4628", "id": "CG-AC:AC1051/ten/ACPE4628", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "1", "narrative": "A systematic review of case reports summarized the clinical findings in 157 individuals with arginase deficiency: \n•Developmental delay: 36.9% \n•Intellectual disability: 55.5%\n•Motor deficits: 80.3%\n•Spasticity: 68.8%\n•Spastic paraplegia (lower limbs): 65%\n•Spastic quadriplegia (lower and upper limbs): 15.9%\n•Progressive spasticity: 7.6%\n•Impaired motor/gait: 38.2%\n•Seizures: 49.7%\n•Vomiting: 29.9%\n•Somatic growth delay: 22.3%\n•Microcephaly: 15.3%", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF003869" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/ten/PGM3050", "id": "CG-AC:AC1051/ten/PGM3050", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "Not provided", "narrative": "The population prevalence of pathogenic variants in ARG1 was not found. The detection rate for pathogenic variants in ARG1 is greater than 98%.\n\nPrevalence based on population carrier frequencies estimated population prevalence of ARG1-D to be 1.4 cases per million people (approximately 1/726,000 people).", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF003862", "CG-AC:RF003864" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/ten/RR2785", "id": "CG-AC:AC1051/ten/RR2785", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "Not provided", "evidenceDomainTag": "Threat Materialization Chances.Relative Risks" }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/ten/EN3138", "id": "CG-AC:AC1051/ten/EN3138", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "Argininemia is characterized by variable degrees of hyperammonemia", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF003862", "CG-AC:RF003863" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/ten/EN3139", "id": "CG-AC:AC1051/ten/EN3139", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "Phenotypic features associated with this condition are based on individuals with severe disease. A phenotypic spectrum exists, and mildly affected individuals exhibit less severe features.", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF003862" ] } ], "tieredRecommendations": [ { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACPM6819", "id": "CG-AC:AC1051/tr/ACPM6819", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Caregiver education \nTo prevent hyperammonemia episodes in individuals with arginase deficiency, the following are recommended: \n•Ongoing education of affected individuals and their caregivers on maintenance; written protocols for maintenance should be provided to parents, primary care providers and pediatricians, and teachers and school staff \n•Treatment protocols and provision of emergency letters to include guidance for care in the event of illness; letters should be provided summarizing key information and principles of emergency treatment and containing contact information for primary treating metabolic center\n•Adequate supplies of specialized dietary products (formulas, medication required for maintenance, and emergency treatment) should always be maintained at home; for any planned travel or vacations, consider contacting a center of expertise near the destination prior to travel dates. \n•MedicAlert bracelet/pendants or car seat stickers", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003862" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACPM6818", "id": "CG-AC:AC1051/tr/ACPM6818", "type": "TieredRecommendation", "evidenceSourceTier": "1", "recommendation": "In a systematic review of case reports of 157 individuals (mean age of diagnosis 6.4 years) with arginase deficiency, dietary protein restriction was the most frequently reported intervention (68% of patients). Nitrogen scavengers were administered to 44.5%. Essential amino acid supplementation was administered to 21%. Liver transplantation was performed in 3.1%. Author-reported clinical improvement was documented for 26% of patients, 15% deteriorated, and 19% had limited or no change; notably, no indication of clinical outcome was reported for 40% cases. A lack of clinical improvement with standard treatments were reported due to difficulty with adherence as well as failure to reach plasma arginine therapeutic goals. Of the patients that had a liver transplantation, none were reported to have died and three achieved normalization of arginine levels up to 10 years after transplantation.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003865" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACCA3789", "id": "CG-AC:AC1051/tr/ACCA3789", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "For patients with arginase deficiency , L-arginine should be avoided for treatment of acute hyperammonemia and acute decompensations, as well as for long-term treatment.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF003287", "CG-AC:RF003866" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACCA3788", "id": "CG-AC:AC1051/tr/ACCA3788", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Valproic acid (exacerbates hyperammonemia) and overhydration (can results in cerebral edema) should be avoided.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF003862" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACPM6825", "id": "CG-AC:AC1051/tr/ACPM6825", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "In those with arginase deficiency and persistent hepatic synthetic function abnormalities, fresh-frozen plasma should be considered prior to surgical procedures.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003862" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACPM6823", "id": "CG-AC:AC1051/tr/ACPM6823", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Surgery Considerations\nFor UCDs, given the risk of acute metabolic decompensation during surgery and general anesthesia, elective surgery should only be carried out in centers able and prepared to deal with hyperammonemic decompensations. The individual should be well, with normal preoperative ammonia and amino acid concentrations and without even minor intercurrent illness. Postsurgical close monitoring of the clinical status and ammonia is required.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003287" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACPM6822", "id": "CG-AC:AC1051/tr/ACPM6822", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In general, for UCDs, emergency regimen for treatment of intercurrent illness is recommended.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003287" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACPM6828", "id": "CG-AC:AC1051/tr/ACPM6828", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Acute management\nThe following are recommended for acute management of arginase deficiency :\n•Management decisions should be based primarily on clinical status. Many patients who present will require admission. If child is shocked or clearly ill, arrange for admission.\n•Conduct initial assessment, including laboratory assessments (pH and gasses, ammonia, urea and electrolytes, full blood count, aminoacids - quantitative, blood culture) \n•Give medications as clinically indicated, including nitrogen scavengers\n•Give IV fluids; potential for need for glucose, saline, potassium; potential for need for insulin under strict supervision. \n•If any clinical sign of incipient encephalopathy, start neurological observations.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003287", "CG-AC:RF003866" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACPM6826", "id": "CG-AC:AC1051/tr/ACPM6826", "type": "TieredRecommendation", "evidenceSourceTier": "1", "recommendation": "A systematic review evaluated management in 291 patients with arginase deficiency from 15 studies. The studies enrolled broader populations, including patients with any type of UCD, so data specific to arginase deficiency were inconsistently and infrequently reported across studies. Included studies represented a broad age range (3-27 years). Of the studies that included age of diagnosis, all indicated that the diagnosis of arginase deficiency was made during childhood (0-9 years). The most widely reported intervention was dietary protein restriction (95% [72 of 76] of patients) followed by nitrogen scavengers (62% [70 out of 113] of patients) and supplementation with essential amino acids (45% [37 out of 82] patients). Standard treatments for ARG1-D were reported as generally ineffective to reduce arginine levels to recommended levels to prevent symptoms or slow progression of disease; plasma arginine levels far exceeded the upper limit of the treatment guidelines.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003869" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACPM6827", "id": "CG-AC:AC1051/tr/ACPM6827", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Since secondary creatine deficiency has been reported in UCDs, creatine supplementation can be used in individuals with low plasma creatine levels.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003287" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACPM6824", "id": "CG-AC:AC1051/tr/ACPM6824", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In general for UCDs, long-term management aims to maintain stable metabolic control, reduce chronic complications, and achieve as close to normal development and growth as possible (Haberle, Tier 2). Nitrogen scavengers (sodium benzoate, sodium phenylbutyrate [PBA] or sodium phenylacetate, glycerol phenylbutyrate) are a mainstay of therapy in individuals with a UCD. Individualized dosing is recommended.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003287", "CG-AC:RF003866", "CG-AC:RF000504" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACPM6820", "id": "CG-AC:AC1051/tr/ACPM6820", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Long term management\nFor arginase deficiency, a standard UCD diet and medical treatment (but without the use of L-arginine), is recommended. Individuals should adhere to a strict protein restriction to reduce plasma arginine levels to as low as possible. Because of the severe natural protein restriction necessary in arginase deficiency, up to 50% of protein supply may be offered as essential amino acids. Vitamin and trace element supplementation may also be required. A specialist metabolic dietitian should be involved.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003287", "CG-AC:RF000504" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACPM6829", "id": "CG-AC:AC1051/tr/ACPM6829", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Following a diagnosis of arginase deficiency , the following evaluations are recommended: \n•Obtain plasma ammonia, amino acid profile, guanidinoacetate, and liver function tests in consultation with a metabolic physician and/or biochemical geneticist \n•Gastroenterology, nutrition, and feeding team evaluation, in consultation with a metabolic dietitian. \n•Developmental assessment\n•Neurologic evaluation \n•Musculoskeletal evaluation.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003862" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACPM6821", "id": "CG-AC:AC1051/tr/ACPM6821", "type": "TieredRecommendation", "evidenceSourceTier": "Not provided", "recommendation": "The American College of Medical Genetics and Genomics (ACMG) has developed an ACT sheet to help clinical decision-making following newborn screening (https://www.acmg.net/PDFLibrary/Arginine.pdf) and during transition to adult health care (https://www.acmg.net/PDFLibrary/Arginase-Deficiency-Transition.pdf).", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF003867", "CG-AC:RF003868" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACSU4094", "id": "CG-AC:AC1051/tr/ACSU4094", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Ongoing monitoring in arginase deficiency includes: \n•Assessment of metabolic control (plasma ammonia, amino acid profile, and nutritional labs) at least monthly for the first year of life and as determined by a metabolic specialist after the first year of life\n•Guanidinoacetate and liver function tests every six to 12 months\n•Monitoring of growth, developmental progress, neurologic evaluation, standardized quality of life assessment for individual and caregivers at each visit.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF003862" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/tr/ACSU4095", "id": "CG-AC:AC1051/tr/ACSU4095", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Individuals with UCDs require lifelong monitoring by a multidisciplinary team. Clinical and biochemical monitoring depends on age and metabolic status. Young and severely affected individuals should be seen at least every 3 months while older or less severely affected individuals may only need annual appointments. Regular review and monitoring of diet, growth, and clinical status are essential.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF003287" ] } ] }, "evidenceCategory": { "outcomeEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/oei", "id": "CG-AC:AC1051/oei", "type": "EvidenceItem", "natureOfTheThreat": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/oei/nott", "id": "CG-AC:AC1051/oei/nott", "type": "EvidenceLine", "prevalenceOfTheGeneticDisorder": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/oei/pgd", "id": "CG-AC:AC1051/oei/pgd", "type": "EvidenceItem", "keyText": "< 1-2 in 100000", "sourceOfPopulation": "General population", "evidenceNarrative": { "@id": "CG-AC:AC1051/en/potgd" } }, "clinicalFeatures": { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/AC1051/oei/cf", "id": 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"id": "CG-AC:RF000501", "type": "Publication", "publicationType": "PMID", "citation": "Haberle J, Boddaert N, Burlina A, Chakrapani A, Dixon M, Huemer M, Karall D, Martinelli D, Crespo PS, Santer R, Servais A, Valayannopoulos V, Lindner M, Rubio V, Dionisi-Vici C. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis. (2012) 7:32.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=22642880", "xdbref": [ "PMID:22642880" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/RF000503", "id": "CG-AC:RF000503", "type": "Publication", "publicationType": "GeneReview", "citation": "N Ah Mew, BC Lanpher, A Gropman, KA Chapman, KL Simpson, , ML Summar. Urea cycle disorders overview. 2003 Apr 29[Updated 2015 Apr 09]. In: RA Pagon, MP Adam, HH Ardinger, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washingtom, Seattle; 1993-2026. ", "webUrl": "https://www.ncbi.nlm.nih.gov/books/NBK1217/", "xdbref": [ "GeneReview:NBK1217", "PMID:20301396" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/RF000504", "id": "CG-AC:RF000504", "type": "Publication", "publicationType": "PMID", "citation": "Consensus statement from a conference for the management of patients with urea cycle disorders. J Pediatr. (2001) 138(1 Suppl):S1-5.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=11148543", "xdbref": [ "PMID:11148543" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/RF003287", "id": "CG-AC:RF003287", "type": "Publication", "publicationType": "PMID", "citation": "Häberle J, Burlina A, Chakrapani A, Dixon M, Karall D, Lindner M, Mandel H, Martinelli D, Pintos-Morell G, Santer R, Skouma A, Servais A, Tal G, Rubio V, Huemer M, Dionisi-Vici C. Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision. J Inherit Metab Dis. (2019) 42(1573-2665):1192-1230.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=30982989", "xdbref": [ "PMID:30982989" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/RF003408", "id": "CG-AC:RF003408", "type": "Publication", "publicationType": "OMIM", "citation": "Online Medelian Inheritance in Man, OMIM. Johns Hopkins University, Baltimore, MD. Argininemia. MIM: 2078002019 Jan 15. ", "webUrl": "https://www.omim.org/entry/207800", "xdbref": [ "OMIM:207800" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/RF003862", "id": "CG-AC:RF003862", "type": "Publication", "publicationType": "PMID", "citation": "Sun A, Crombez EA, Wong D. Arginase Deficiency. (1993)", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=20301338", "xdbref": [ "PMID:20301338" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/RF003863", "id": "CG-AC:RF003863", "type": "Publication", "publicationType": "Orphanet", "citation": "Argininemia. Orphanet encyclopedia [Internet]", "xdbref": [ "Orphanet:90" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/RF003864", "id": "CG-AC:RF003864", "type": "Publication", "publicationType": "PMID", "citation": "Catsburg C, Anderson S, Upadhyaya N, Bechter M. Arginase 1 Deficiency: using genetic databases as a tool to establish global prevalence. Orphanet J Rare Dis. (2022) 17(1750-1172):94.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=35236361", "xdbref": [ "PMID:35236361" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/RF003865", "id": "CG-AC:RF003865", "type": "Publication", "publicationType": "PMID", "citation": "Bin Sawad A, Pothukuchy A, Badeaux M, Hodson V, Bubb G, Lindsley K, Uyei J, Diaz GA. Natural history of arginase 1 deficiency and the unmet needs of patients: A systematic review of case reports. JIMD Rep. (2022) 63(2192-8304):330-340.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=35822089", "xdbref": [ "PMID:35822089" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/RF003866", "id": "CG-AC:RF003866", "type": "Publication", "publicationType": "Other", "citation": "true. Hyperammonia due to arginase deficiency. Bimdg. (2008) ", "webUrl": "https://bimdg.org.uk/" }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/RF003867", "id": "CG-AC:RF003867", "type": "Publication", "publicationType": "Other", "citation": "true. Increased arginine - argininemia. (2000) ", "webUrl": "https://www.acmg.net/PDFLibrary/Arginine.pdf" }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/RF003868", "id": "CG-AC:RF003868", "type": "Publication", "publicationType": "Other", "citation": "true. Arginase deficiency. (2000) ", "webUrl": "https://www.acmg.net/PDFLibrary/Arginase-Deficiency-Transition.pdf" }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/RF003869", "id": "CG-AC:RF003869", "type": "Publication", "publicationType": "PMID", "citation": "Bin Sawad A, Jackimiec J, Bechter M, Trucillo A, Lindsley K, Bhagat A, Uyei J, Diaz GA. Epidemiology, methods of diagnosis, and clinical management of patients with arginase 1 deficiency (ARG1-D): A systematic review. Mol Genet Metab. (2022) 137(1096-7206):153-163.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=36049366", "xdbref": [ "PMID:36049366" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Pediatric/api/sepio/doc/RF003870", "id": "CG-AC:RF003870", "type": "Publication", "publicationType": "OMIM", "citation": "Online Medelian Inheritance in Man, OMIM. Johns Hopkins University, Baltimore, MD. Arginase 1; arg1. MIM: 6083132022 Mar 11. ", "webUrl": "https://www.omim.org/entry/608313", "xdbref": [ "OMIM:608313" ] } ] }