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Ornithine transcarbamylase (OTC) deficiency is well known as the most common inherited disorder of the urea cycle, and 1 of the most common causes of hyperammonemia in newborns. We experienced a case of a 3-day-old boy with OTC deficiency who appeared healthy in the first 2 days of life but developed lethargy and seizure soon afterwards. His serum...
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Context 1
... showed no abnormalities. The electroence phalogram suggested moderate to severe encephalopathy. A genetic study confirmed the diagnosis of OTC deficiency. A single nucleotide change from G to A was discovered (c.422G>A) and this change resulted in missesnse mutation, aminoacid change from arginine to glutamine at codon 141 (p.Arg 141 Gln) (Fig. ...Similar publications
Background:
Ornithine transcarbamylase is an enzyme of the urea cycle, which produces urea from ammonia. Although ornithine transcarbamylase deficiency mainly occurs as a severe neonatal-onset disease, a late-onset form that could become symptomatic from infancy to adulthood is also known.
Case presentation:
A 34-year-old man presented with sudd...
Citations
... Using their strategy, the patient's ammonia was reduced from a peak of >1, to 422 µg/dl at 24 h, and 222 µg/dl at 57 h. The patient had a rebound in ammonia 364 µg/dl after 5 days of dialysis and therefore continued on CRRT until 7 days (15). Another case series by Santa Maria et al. included six newborns with UCDs who were placed on CRRT. ...
Objectives: This study aims to assess the feasibility of using hemofiltration for ammonia clearance in low body weight infants with an inborn error of metabolism.
Design: A study of two cases.
Setting: Quaternary pediatric hospital (Saint Louis Children's Hospital) NICU and PICU.
Patients: Infants <6 months of age with an ICD-9 diagnosis of 270.6 (hyperammonemia).
Interventions: Continuous renal replacement therapy (CRRT).
Measurements and Main Results: We measure serum ammonia levels over time and the rate of ammonia clearance over time. Continuous renal replacement therapy was more effective than scavenger therapy alone (Ammonul™) for rapid removal of ammonia in low weight infants (as low as 2.5 kg).
Conclusions: Continuous renal replacement therapy is technically feasible in low weight infants with severe hyperammonemia secondary to an inborn error of metabolism.
... In neonates with hyperammonemia caused by an inborn error of metabolism, a few studies have suggested that PD, intermittent HD, and CRRT are effective modalities to decrease plasma level of ammonia. 4,[7][8][9][10][11][12] However, there is little data on the optimal modality, prescription, or prognostic factors associated with RRT in neonates with hyperammonemia. In the following A c c e p t e d A r t i c l e review, we discuss the current literature on the use of RRT for treating neonates with hyperammonemia caused by an inborn error of metabolism, including optimal prescriptions, prognosis, and outcomes. ...
Hyperammonemia can caused by several different genetic inborn errors of metabolism including urea cycle defects, organic acidemias, fatty acid oxidation defects, and certain disorders of amino acid metabolism. High levels of ammonia are extremely neurotoxic, leading to astrocyte swelling, brain edema, coma, severe disability, and even death. Thus, emergency treatment for hyperammonemia must begin before a precise diagnosis is established. In neonates with hyperammonemia caused by an inborn error of metabolism, a few studies have suggested that peritoneal dialysis, intermittent hemodialysis, and continuous renal replacement therapy are effective modalities for decreasing plasma level of ammonia. In this review, we discuss the current literature related to the use of renal replacement therapy for treating neonates with hyperammonemia caused by an inborn error of metabolism, including optimal prescriptions, prognosis, and outcomes. We also review the literature on new technologies and instrumentation for renal replacement therapy in small babies.
... Approximately 84% of mutations are single base substitution mutations, 12% are small-fragment deletions or insertion mutations, and 4% are large-fragment deletion mutations. Approximately 42% of mutations are associated with disease onset during the neonatal stage, 21% with late disease onset, and 37% with disease onset in females [7,[14][15][16][17][18][19]. ...
Background
The aim of this study was to perform gene detection in 2 clinical cases of highly suspected ornithine transcarbamylase deficiency (OTCD) pediatric patients by first-generation sequencing technology in order to confirm the pathogenic genetic factors of their families and allow the families to undergo genetic counselling and prenatal diagnosis.
Material/Methods
The peripheral DNA samples of 2 children with highly suspected OTCD (the probands) and their parents were collected. DNA fragments corresponding to exons 1–10 of the OTC gene from the samples were amplified using polymerase chain reaction (PCR), and then subjected to Sanger sequencing to confirm the pathogenic mutation sites.
Results
The probands were both confirmed to have OTCD. The proband in Family 1 was a male carrying a c.867+1G>C mutation at a splice site within the OTC gene. The gene detection results of amniotic fluid cells at 16 weeks of pregnancy showed that the fetus was a male who also carried the c.867+1G>C mutation. The proband in Family 2 was a male carrying a c.782T>C(p. I261T) mutation in the OTC gene. The gene detection results of amniotic fluid cells at 18 weeks showed that the fetus was a male without pathogenic mutations in the OTC gene. The gene detection results of peripheral blood from the fetus after birth were consistent with those obtained from amniotic fluid cells.
Conclusions
Pediatric children who are clinically suspected of OTCD can receive a definitive diagnosis through OTC gene detection.
Kidney support therapy (KST), previously referred to as Renal Replacement Therapy, is utilized to treat children and adults with severe acute kidney injury (AKI), fluid overload, inborn errors of metabolism, and kidney failure. Several forms of KST are available including peritoneal dialysis (PD), intermittent hemodialysis (iHD), and continuous kidney support therapy (CKST). Traditionally, extracorporeal KST (CKST and iHD) in neonates has had unique challenges related to small patient size, lack of neonatal-specific devices, and risk of hemodynamic instability due to large extracorporeal circuit volume relative to patient total blood volume. Thus, PD has been the most commonly used modality in infants, followed by CKST and iHD. In recent years, CKST machines designed for small children and novel filters with smaller extracorporeal circuit volumes have emerged and are being used in many centers to provide neonatal KST for toxin removal and to achieve fluid and electrolyte homeostasis, increasing the options available for this unique and vulnerable group. These new treatment options create a dramatic paradigm shift with recalibration of the benefit: risk equation. Renewed focus on the infrastructure required to deliver neonatal KST safely and effectively is essential, especially in programs/units that do not traditionally provide KST to neonates. Building and implementing a neonatal KST program requires an expert multidisciplinary team with strong institutional support. In this review, we first describe the available neonatal KST modalities including newer neonatal and infant-specific platforms. Then, we describe the steps needed to develop and sustain a neonatal KST team, including recommendations for provider and nursing staff training. Finally, we describe how quality improvement initiatives can be integrated into programs.
Hyperammonaemia in children can lead to grave consequences in the form of cerebral oedema, severe neurological impairment and even death. In infants and children, common causes of hyperammonaemia include urea cycle disorders or organic acidaemias. Few studies have assessed the role of extracorporeal therapies in the management of hyperammonaemia in neonates and children. Moreover, consensus guidelines are lacking for the use of non-kidney replacement therapy (NKRT) and kidney replacement therapies (KRTs, including peritoneal dialysis, continuous KRT, haemodialysis and hybrid therapy) to manage hyperammonaemia in neonates and children. Prompt treatment with KRT and/or NKRT, the choice of which depends on the ammonia concentrations and presenting symptoms of the patient, is crucial. This expert Consensus Statement presents recommendations for the management of hyperammonaemia requiring KRT in paediatric populations. Additional studies are required to strengthen these recommendations. This expert Consensus Statement from the Pediatric Continuous Renal Replacement Therapy (PCRRT) workgroup presents recommendations for the management of hyperammonaemia requiring kidney replacement therapy in paediatric populations. Additional studies are needed to strengthen these recommendations, which will be reviewed every 2 years.
Inborn errors of metabolism are infrequent, but they are life-threatening. Early detection and awareness of symptoms within the very first few hours of clinical presentation may save the life of a child. For any child with unexplained vomiting, change in mental status, seizures, developmental delay, or loss of milestones, genetic and metabolic disorders must be in the differential diagnosis. All pediatricians must be familiar with the results of the newborn screening, which must be reported to them promptly, and must know the best next step for any abnormal result.
Hyperammonemia, characterized by excess ammonia in the blood, can be a life-threatening condition. Clinical symptoms are nonspecific, and include poor feeding, lethargy, irritability, tachypnea, seizures, obtundation, and respiratory insufficiency. Hyperammonemia is due to defect in detoxification or overproduction of ammonia. Defects in the urea cycle lead to the most severe hyperammonemia. Other causes of hyperammonemia include various metabolic defects such as certain organic acidurias, fatty acid oxidation defects, drugs and liver disease. The most important diagnostic test for the diagnosis of hyperammonemia is measuring plasma ammonia. Various biomarkers are used for the differential diagnosis of hyperammonia. They include plasma and urine amino acid profiles, urine organic acid profiles, and plasma acylcarnitine profiles. Management of acute hyperammonia includes discontinuation of protein intake, and treatment with nitrogen scavengers and glucose. Arginine is administrated in all urea cycle defects except arginase deficiency. Disease follow-up biomarkers include plasma ammonia levels, specific amino acids, and urine orotic acid. Since patients are on a low protein diet, markers of nutritional deficiency are also monitored.
Continuous renal replacement therapy (CRRT) is a mode of renal replacement therapy that is used for hemodynamic instable, fluid overload, and septic patients complicated by AKI in the critical care/intensive care unit setting. CRRT provides a slow, gentle treatment of AKI and fluid removal much like the native kidney (ultrafiltration up to 120 mL/h) and is generally well tolerated by critically ill, hemodynamically unstable patients. The CRRT is intended to substitute for impaired renal function over an extended period of time and applied for 24 h a day. It provides slower solute clearance per unit time as compared with intermittent hemodialysis therapies, but over 24 h may even exceed clearances with intermittent hemodialysis. CRRT differs considerably from intermittent hemodialysis, relying heavily upon continuous ultrafiltration of plasma water. It has the potential for removal of large quantities of larger-molecular-weight drugs, such as glycopeptide antibiotics, from plasma. Moreover, control of anemia, acid–base balance, and fluid volume can be achieved easily and continuously maintained with CRRT. In addition, CRRT removes inflammatory mediators of sepsis such as TNF-alpha, interleukin, and complement. CRRT can be performed with ultrafiltration (SCUF), hemofiltration (CVVH), or hemodialysis (CVVHD) or a combination of both techniques (CVVHDF). Of these, the CVVH and CVVHD are often used in children requiring CRRT. Potential benefits of CRRT in patients with multiple organ dysfunctions include management of fluid balance, decreasing fluid overload, removal of inflammatory mediators, enhanced nutritional support, and control of electrolyte and acid–base abnormalities.
Below we have summarized our experience treating ten children with severe AKI complicated by sepsis, hyperkalemia, diuretic-resistant fluid overload, inborn error of metabolism, and/or organ dysfunction syndromes (MODS) treated with CRRT. All ten recovered completely, thus supporting the effectiveness of CRRT for the management of children who are critically ill due to AKI complicated by MODS.
