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Table of Contents
Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 24-27

Continuous renal replacement therapy in a preterm neonate with hyperammonemia secondary to a rare disease

1 Pediatric Nephrology Section, Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
2 Pediatric Nephrology Section, Department of Pediatrics, King Faisal Specialist Hospital and Research Centre; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
3 College of Medicine, Alfaisal University; Pediatric Critical Care Section, Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
4 Pediatric Critical Care Section, Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
5 Department of Ambulatory Care Nursing, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Date of Submission28-Mar-2020
Date of Decision10-Apr-2020
Date of Acceptance16-May-2020
Date of Web Publication27-Jun-2020

Correspondence Address:
Weiam Almaiman
Department of Pediatrics (MBC 58), King Faisal Specialist Hospital and Research Center, P.O.B. 3354, Riyadh 11211; College of Medicine, Alfaisal University, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AJPN.AJPN_9_20

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We report a newborn baby girl with a rare cause of hyperammonemia, in which a session of continuous renal replacement therapy (CRRT) was performed successfully despite the child's small size. The baby was born at 34 weeks' gestation with a birth weight of 2.2 kg and was referred on day 4 of life with lethargy, bradycardia, hypothermia, hypoglycemia, and metabolic acidosis associated with hyperammonemia. Following the insertion of the GamCath line, CRRT was performed using continuous venovenous hemodialysis modality, Ultraflux AV Paed dialyzer (Fresenius Medical Care), and multiFiltrate pediatric kit. Over 19 h of therapy, serum ammonia level reduced from >700 μmol/L to 103 μmol/L. Next-generation sequencing revealed a homozygous pathogenic variation in SLC25A20 (NM_000387; exon2; c.109C>T; p.R37X), leading to a diagnosis of carnitine-acylcarnitine translocase deficiency. The child succumbed during a subsequent hospital stay. This case instructively informs on the feasibility and efficacy of CRRT in the management of neonatal hyperammonemia.

Keywords: Carnitine-acylcarnitine translocase, CRRT, CVVH, newborn

How to cite this article:
Sebeih Y, Alsabban E, Alanzi F, Skaff C, Asiry R, Alwahsh M, Almaiman W. Continuous renal replacement therapy in a preterm neonate with hyperammonemia secondary to a rare disease. Asian J Pediatr Nephrol 2020;3:24-7

How to cite this URL:
Sebeih Y, Alsabban E, Alanzi F, Skaff C, Asiry R, Alwahsh M, Almaiman W. Continuous renal replacement therapy in a preterm neonate with hyperammonemia secondary to a rare disease. Asian J Pediatr Nephrol [serial online] 2020 [cited 2022 Jul 7];3:24-7. Available from: https://www.ajpn-online.org/text.asp?2020/3/1/24/288155

  Introduction Top

Hyperammonemia, defined as a blood ammonia level of ≥80 μmol/L in newborns, is a life-threatening condition, which might cause permanent neurological insult.[1] Hyperammonemia, with a level >500 μmol/L, needs prompt action by a multidisciplinary team, including metabolic, nephrology, and critical care physicians, to facilitate necessary management including initiation of continuous renal replacement therapy (CRRT). CRRT is considered superior to continuous peritoneal dialysis since it achieves a faster reduction of toxin blood levels.[2] CRRT requires close monitoring of vital signs and for bleeding tendency, which can worsen during the procedure.[3] We report the acute management of hyperammonemia caused by a rare disease in a preterm low birth weight neonate using CRRT.

  Case Report Top

A girl neonate weighing 2.2 kg was born at 34-weeks' gestation, to a second-gravida 40-year-old female with a history of secondary infertility for 20 years, following preterm rupture of membrane for >18 h. The baby was delivered in another institution through spontaneous vaginal delivery and had Apgar scores of 7 and 9 at 1 and 5 min of life. As per hospital protocol, the baby was admitted to the nursery and was started on regular formula apart from being breastfed. On day 4 of life, the baby developed bradycardia, hypothermia, hypoglycemia, and lethargy, requiring transfer to the neonatal intensive care unit (ICU). Blood and urine cultures were performed, and therapy with intravenous ampicillin and gentamicin was initiated. Blood investigations revealed pH 7.27 (normal range 7.30–7.40), HCO3 15 (22–31) mmol/L, lactate 3.2 (0.05–2) mmol/L, and ammonia >700 (<55) μmol/L. Evaluation for arrhythmias, dyselectrolytemia, and hospital-acquired pneumonia was noncontributory, based on serum electrolytes, electrocardiography (ECG), and chest radiography; echocardiography revealed a small ASD. For further management, the child was transferred to our tertiary care center.

The neonate was admitted to our pediatric ICU with encephalopathy (Glasgow Coma Scale 8). Pupils were 4 mm and very sluggishly reactive to light. The anterior fontanelle was soft and flat. Upon admissions, the temperature was 36.6°C, heart rate 154 beats/min, blood pressure 73/41 mm Hg, and respiratory rate 59 breaths/min. Breathing was irregular, shallow, and with frequent hiccups; hence, mechanical ventilation was initiated. Initial evaluation revealed blood sugar 2.3 (normal 2.5–7.0 mmol/L) and anion gap metabolic acidosis with high lactate. Serum levels of urea, creatinine, calcium, phosphate, and liver function tests and complete blood counts were within the range for age. The serum ammonia level was >700 μmol/L, based on which a decision to initiate CRRT was taken [Table 1].
Table 1: The protocol of acute management of hyperammonemia in Middle East[5]

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Following a failed attempt to secure central venous access in the right internal jugular vein, a double-lumen catheter (GamCath) of size 6.5 Fr and length 10 cm was inserted in the left internal jugular vein. CRRT was initiated with continuous venovenous hemodialysis as the modality, using Ultraflux AV Paed dialyzer and multiFiltrate pediatric kit. The circuit was primed with packed red cells, as its volume (filter volume 18 ml; blood lines 54 ml) was higher than 10% of the child's blood volume. The dialysate solution, with potassium concentration of 2 mmol/L and temperature of 36.5°C, was run at a rate of 100 ml/h. The blood flow rate was kept at 50 ml/min, and regular heparin was administered as anticoagulant (in an initial bolus of 20 U/kg followed by maintenance dose of 10 U/kg/h).

CRRT was associated with adverse events. While there was no hypothermia or arrhythmia, hypotension was observed at about 12 h of therapy. Systolic and diastolic blood pressure ranged from 50 to 58 mmHg and 24 to 30 mmHg, respectively, with a mean arterial blood pressure of 29–32 mmHg.[4] Hypotension was unresponsive to a bolus of normal saline at 20 ml/kg; hence, dopamine was administered as an infusion at 6 μg/kg/min, and was continued for 6 h during which hemodynamic stability was maintained. Blood pH, electrolytes, complete blood counts, and coagulation parameters (except activated clotting time, which was not available) were monitored every 2–4 h, as shown in [Table 2]. Three boluses of potassium chloride, at 1 mmol/kg each, were required for refractory hypokalemia (lowest potassium 2.3 mmol/L), and a bolus of calcium gluconate at 100 mg/kg was administered for hypocalcemia (serum calcium 1.6 mmol/L). At 12 h of therapy, heparin was discontinued in view of prolonged prothrombin time (international normalized ratio 3.1), prolonged partial thromboplastin time (73.2 s), and transient thrombocytopenia (42,000/μL); this was followed by circuit clotting.
Table 2: Laboratory work-ups before, 12 h after start of, and at the end of, continuous renal replacement therapy

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Serum ammonia level was monitored sequentially and fell to 103 μmol/L after 19 h of CRRT [Figure 1]a and [Figure 1]b. Since a tenable diagnosis had not been reached, following discussion with the metabolic team, in view of stabilization of ammonia level and the adverse events associated with CRRT, and in accordance with the guidelines on the acute management of hyperammonemia in the Middle East region [Table 1], the procedure was discontinued.[5] After 48 h of discontinuing CRRT, the neonate was extubated, having had improved consciousness and a normal breathing pattern, attributed to correction of encephalopathy secondary to hyperammonemia. At this time, the serum ammonia level was 55 μmol/L [Figure 1].
Figure 1: Blood levels of ammonia (a) during, and (b) after discontinuing, continuous renal replacement therapy (CRRT)

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On the next day, the neonate developed hypoxemia requiring intubation and mechanical ventilation. Despite high settings of ventilatory support, following transient hemodynamic stability of a few hours, her condition deteriorated. Hypoxemia (oxygen saturation 50%) with tachycardia (heart rate 230–240 beats/min) was associated with ECG finding of wide-QRS ventricular tachycardia. Despite therapy for arrhythmia and resuscitative measures in accordance with the pediatric advanced life support guidelines, including prolonged cardiopulmonary resuscitation, there was pulseless electrical activity leading to patient death. Serum ammonia level in sample drawn during resuscitation was normal (73 μmol/L). Death was attributed to the arrhythmia, which was likely secondary to an underlying primary metabolic disease. Next-generation sequencing, performed on DNA from the stored sample, revealed a homozygous loss-of-function (pathogenic) variant in exon 2 of SLC25A20 (NM_000387; c.109C > T: p. R37X), indicating a diagnosis of carnitine-acylcarnitine translocase (CACT) deficiency.

  Discussion Top

Newborns with hyperammonemia and weight <5 kg can undergo acute hemodialysis using special circuits and equipments, which carry a low risk of complications such as hypotension, dyselectrolytemia, and technical problems.[6] Continuous venovenous hemofiltration using Prismaflex systems is performed for neonatal hyperammonemia as an acute measure, and reduces the risk of chronic neurological sequelae.[7] As compared to the case series by Cavagnaro et al.,[7] we successfully achieved the acceptable level of ammonia in a short duration of within 12 h, by CRRT using the Ultraflux AV Paed dialyzer. The procedure was overall uneventful apart from an episode each of transient circuit clotting and hypotension, which are known complications, and were managed satisfactorily, allowing the procedure to be continued. Catheter-related complications are observed in approximately 3% of newborn patients. Asymptomatic hypokalemia, described in 4% of newborns on CRRT,[8] and hypocalcemia, were detected through close monitoring, and managed satisfactorily with intravenous supplements. Heparin, used to anticoagulate the circuit, was discontinued temporarily due to abnormal coagulation parameters and transient thrombocytopenia, which are common complications of heparin use in CRRT.[8] We could not monitor activated clotting time (ACT), considered a useful indicator of circuit coagulability, due to the assay's nonavailability. There was mild and brief hemodynamic instability, likely due to the large extracorporeal volume of the circuit, and was managed with dopamine infused at 6 μg/kg/min. Overall, the procedure of CRRT was well tolerated and effective, leading to a stable decline in serum ammonia levels.

Despite a stable reduction in serum ammonia levels to below 100–150 μmol/L, the child had a sudden tachyarrhythmia that led to death. The arrhythmia can be explained by the underlying disease, CACT deficiency. This rare inherited disease is a type of fatty acid oxidation disorder and is associated with high mortality risk.[9] Newborns with CACT deficiency are reported to present with severe hyperammonemia, hypoglycemia, dysrhythmias, and sudden cardiac death associated with neurological injury.[10],[11] The homozygous loss of function variant of SLC25A20 found in our patient is classified as pathogenic, using the criteria of the American College of Medical Genetics and Genomics, and is consistent with the autosomal recessive pattern of inheritance reported for CACT deficiency.[12],[13] However, we could not perform Sanger sequencing to validate the presence of the variant in the child nor confirm the parents as heterozygous carriers.

  Conclusion Top

Preterm low-birth-weight neonates with acute severe hyperammonemia can be managed safely on CRRT with satisfactory reduction in serum ammonia levels, using pediatric tubings and dialyzers, priming of the circuit, and close monitoring for complications.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Savy N, Brossier D, Brunel-Guitton C, Ducharme-Crevier L, Du Pont-Thibodeau G, Jouvet P. Acute pediatric hyperammonemia: Current diagnosis and management strategies. Hepat Med 2018;10:105-15.  Back to cited text no. 1
Arbeiter AK, Kranz B, Wingen AM, Bonzel KE, Dohna-Schwake C, Hanssler L, et al. Continuous venovenous haemodialysis (CVVHD) and continuous peritoneal dialysis (CPD) in the acute management of 21 children with inborn errors of metabolism. Nephrol Dial Transplant 2010;25:1257-65.  Back to cited text no. 2
Nishimi S, Sugawara H, Onodera C, Toya Y, Furukawa H, Konishi Y, et al. Complications during continuous renal replacement therapy in critically Ill neonates. Blood Purif 2019;47 Suppl 2:74-80.  Back to cited text no. 3
American Academy of Pediatrics 2017. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 2017;140:E20171904.  Back to cited text no. 4
Alfadhel M, Mutairi FA, Makhseed N, Jasmi FA, Al-Thihli K, Al-Jishi E, et al. Guidelines for acute management of hyperammonemia in the Middle East region. Ther Clin Risk Manag 2016;12:479-87.  Back to cited text no. 5
Sadowski RH, Harmon WE, Jabs K. Acute hemodialysis of infants weighing less than five kilograms. Kidney Int 1994;45:903-6.  Back to cited text no. 6
Cavagnaro Santa María F, Roque Espinosa J, Guerra Hernández P. Continuous venovenous hemofiltration in neonates with hyperammonemia. A case series. Rev Chil Pediatr 2018;89:74-8.  Back to cited text no. 7
Sohn YB, Paik KH, Cho HY, Kim SJ, Park SW, Kim ES, et al. Continuous renal replacement therapy in neonates weighing less than 3 kg. Korean J Pediatr 2012;55:286-92.  Back to cited text no. 8
Korman SH, Pitt JJ, Boneh A, Dweikat I, Zater M, Meiner V, et al. A novel SLC25A20 splicing mutation in patients of different ethnic origin with neonatally lethal carnitine-acylcarnitine translocase (CACT) deficiency. Mol Genet Metab 2006;89:332-8.  Back to cited text no. 9
Longo N, Amat di San Filippo C, Pasquali M. Disorders of carnitine transport and the carnitine cycle. Am J Med Genet C Semin Med Genet 2006;142C: 77-85.  Back to cited text no. 10
Auron A, Brophy PD. Hyperammonemia in review: Pathophysiology, diagnosis, and treatment. Pediatr Nephrol 2012;27:207-22.  Back to cited text no. 11
Saudi Mendeliome Gorup. Comprehensive gene panels provide advantages over clinical exome sequencing for Mendelian diseases. Genome Biol 2015;16:226.  Back to cited text no. 12
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-24.  Back to cited text no. 13


  [Figure 1]

  [Table 1], [Table 2]


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