Transient hyperammonemia of the newborn

Last updated
Transient hyperammonemia of the newborn
Specialty Neonatology

Transient hyperammonemia of the newborn (THAN) is an idiopathic disorder occasionally present in preterm newborns but not always symptomatic. [1] Continuous dialysis or hemofiltration have proven to be the most effective treatment. [1] [2] Nutritional support and sodium benzoate have also been used to treat THAN. [2]

Contents

Signs and symptoms

Hyperammonemia occurs when the body produces excess ammonia. This ammonia primarily exists as ammonium ion that has a concentration less than or around 35 μmol/L in normal referenced serum levels. [3] Excess ammonia is processed in the liver through the urea cycle to produce urea. [3] Excess ammonia can be produced by bacterial hydrolysis of intestinal compounds, purine nucleotide cycles, the transamination of amino acid in voluntary muscles, and other metabolic events of filtration organs(kidneys and liver). [3] In THAN, symptoms of hyperammonemia are observed within 24 hours of birth, and the causation of hyperammonemia must exclude urea cycle disorders. If the amount of ammonia entering the brain is increased, neurological disorders such as urea cycle enzyme deficiencies, Reye syndrome, seizures, and encephalopathies may occur. [3] The most common indicator of THAN is respiratory distress syndrome. In newborns with THAN, the primary cause is thought to be genetic, but it has not been narrowed down to one gene or locus so the exact cause remains unknown. [4] Observable CNS depression, comatose, metabolic acidosis, feeding difficulties, cyanosis, abnormal EEG, increased intraventricular hemorrhage, hypotonia, and irratibility are common symptoms of THAN. Individuals that develop hyperammonemia after birth are more likely to have hyperammonemia as a result in urea cycle enzyme deficiency (UCED). [4]

Pathophysiology

The pathophysiology for this disorder is mostly unknown but there have been a few propositions for its origin. One study suggested that a transient platelet activation of the infant's portal system is responsible for this hyperammonemia. [5] Another study proposed that this occurs due to a shunting of blood away from the portal system of the liver through the ductus venosus directly into the systemic circulation. This causes the blood to skip the step of ammonia removal in the liver. [5]

Diagnosis

Since the etiology is unconfirmed, diagnosis is generally accomplished when there is hyperammonemia present within 24–36 hours of birth and urea cycle defects can be excluded. [5] Organic acidemias and other metabolic errors must also be excluded. The diagnostic criteria for hyperammonemia is ammonia blood levels higher than 35 μmol/L. This is accomplished by observing urine ketones, organic acids, enzyme levels and activities, and plasma and urine amino acids. [5] Mild Transient Hyperammonemia is diagnosed when ammonia levels are between 40-50 μM, lasts for about 6–8 weeks, and has no related neurological problems. Severe Transient Hyperammonemia is diagnosed when ammonia levels are above 50 μM up to as much as 4000 μM. Severe Transient Hyperammonemia causes neurological problems as ammonia levels in the brain are too high, which can cause infant hyptotonia as well as neonatal seizures. [5] Severe Transient Hyperammonemia can also cause respiratory distress syndrome. [5] Chest x-rays may resemble hyaline membrane disease. [5]

Differentiating between UCED and THAN

A study was done by Hudak to find the differences between transient hyperammonemia of the newborn (THAN) and urea cycle enzyme deficiency(UCED) on 33 THAN victims and 13 UCED victims. [6] Some of the clinical findings were not able to be measured in the THAN patients due to lack of equipment or lack of reported information in these 33 cases, so the numbers shown represent the number of positive clinical findings/out of the number cases in which the symptom could be observed or was documented. The results were as follows: Respiratory distress occurred in 22/23 of THAN patients and only in 0/13 of UCED patients. [6] Abnormal chest radiographs were found in 23/25 THAN victims, and 0/9 in UCED patients. [6] The gestational age was less than 36 weeks in 25/31 THAN patients, but only 1/13 UCED patients. [6] The birthweight was less than 2.5 kg in 27/31 THAN patients and in 2/12 UCED patients. [6] A coma that lasted 48 hours or longer occurred in 12/17 THAN patients but only occurred in 1/12 UCED patients. [6] Free ammonia (NH4+) levels greater than 1500 μM occurred in 17/29 THAN patients but only 1/13 UCED patients. [6]

Treatment

Although the etiology is unconfirmed, transient hyperammonemia is known to be caused by increased levels of ammonia in the blood stream, as well as a failure of the urea cycle to convert enough of the ammonia into urea. [5] Since transamination of proteins is a leading producer of ammonia, protein restriction may be recommended as a therapy to reduce the symptoms of the episode. THAN can also be treated by avoiding amino acids in TPN or total parenteral nutrition or by giving a high caloric diet to limit catabolism of the tissues and therefore to minimize the breakdown of endogenous protein. [4] The most common treatments are dialysis (both peritoneal and hemodialysis), sodium benzoate, and arginine. [5] Sodium Benzoate combines with glycine to be excreted in the form of hippuric acid. [5] The goal of these treatments is to convert nitrogen to a compound that can be excreted more easily. [5]

Prognosis

The mortality rate for THAN is relatively high unless immediate treatment is obtained. [5] The duration of hyperammonemia is directly correlated to morbidity as well as the associated neurological conditions. [5] After the first hyperammonemic episode, there is no increased risk for future hyperammonemic episodes, and normal protein consumption can be continued. [4]

Epidemiology

Although this data may be underestimated as a result of misdiagnosis and failure to report illnesses in fatal cases, the current estimates are fairly representative of neonates with hyperammonemia. [3] The United States has an estimated frequency of UCED of 1 per 25,000 live births. [3] The international prevalence is between an estimated 1:8,000-1:44,000, varying widely by location. [3] In order for THAN to be diagnosed, urea cycle deficiencies must be excluded, and the diagnosis must be made within 24–36 hours of birth. In 1996, one study said that there were only a confirmed 33 cases of THAN worldwide in literature. [5] This study also admitted that at first they did not consider the possibility that the infant did not have a urea cycle deficiency. [5] The hospital that this case occurred in did not have equipment to measure urea cycle enzymes, so they confirmed the diagnosis post mortem with an autopsy. [5] Therefore, it is important to consider that many infants diagnosed with regular hyperammonemia, may have actually had THAN, but the urea cycle deficiency was not excluded and therefore did not meet the criteria for diagnosis. [7]

Related Research Articles

The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). Animals that use this cycle, mainly amphibians and mammals, are called ureotelic.

<span class="mw-page-title-main">Ornithine transcarbamylase</span> Mammalian protein found in Homo sapiens

Ornithine transcarbamylase (OTC) is an enzyme that catalyzes the reaction between carbamoyl phosphate (CP) and ornithine (Orn) to form citrulline (Cit) and phosphate (Pi). There are two classes of OTC: anabolic and catabolic. This article focuses on anabolic OTC. Anabolic OTC facilitates the sixth step in the biosynthesis of the amino acid arginine in prokaryotes. In contrast, mammalian OTC plays an essential role in the urea cycle, the purpose of which is to capture toxic ammonia and transform it into urea, a less toxic nitrogen source, for excretion.

<span class="mw-page-title-main">Methylmalonic acidemia</span> Medical condition

Methylmalonic acidemia, also called methylmalonic aciduria, is an autosomal recessive metabolic disorder that disrupts normal amino acid metabolism. It is a classical type of organic acidemia. The result of this condition is the inability to properly digest specific fats and proteins, which in turn leads to a buildup of a toxic level of methylmalonic acid in the blood.

Propionic acidemia, also known as propionic aciduria or propionyl-CoA carboxylase deficiency, is a rare autosomal recessive metabolic disorder, classified as a branched-chain organic acidemia.

<span class="mw-page-title-main">Hyperammonemia</span> Medical condition

Hyperammonemia is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to brain injury and death. It may be primary or secondary.

<span class="mw-page-title-main">Ornithine transcarbamylase deficiency</span> Medical condition

Ornithine transcarbamylase deficiency also known as OTC deficiency is the most common urea cycle disorder in humans. Ornithine transcarbamylase, the defective enzyme in this disorder is the final enzyme in the proximal portion of the urea cycle, responsible for converting carbamoyl phosphate and ornithine into citrulline. OTC deficiency is inherited in an X-linked recessive manner, meaning males are more commonly affected than females.

Protein toxicity is the effect of the buildup of protein metabolic waste compounds, like urea, uric acid, ammonia, and creatinine. Protein toxicity has many causes, including urea cycle disorders, genetic mutations, excessive protein intake, and insufficient kidney function, such as chronic kidney disease and acute kidney injury. Symptoms of protein toxicity include unexplained vomiting and loss of appetite. Untreated protein toxicity can lead to serious complications such as seizures, encephalopathy, further kidney damage, and even death.

<span class="mw-page-title-main">Maple syrup urine disease</span> Autosomal recessive metabolic disorder

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia. The condition gets its name from the distinctive sweet odor of affected infants' urine and earwax, particularly prior to diagnosis and during times of acute illness.

<span class="mw-page-title-main">Citrullinemia</span> Medical condition

Citrullinemia is an autosomal recessive urea cycle disorder that causes ammonia and other toxic substances to accumulate in the blood.

<span class="mw-page-title-main">Carnitine palmitoyltransferase II deficiency</span> Medical condition

Carnitine palmitoyltransferase II deficiency is an autosomal recessively inherited genetic metabolic disorder characterized by an enzymatic defect that prevents long-chain fatty acids from being transported into the mitochondria for utilization as an energy source. The disorder presents in one of three clinical forms: lethal neonatal, severe infantile hepatocardiomuscular and myopathic.

<span class="mw-page-title-main">Argininosuccinic aciduria</span> Medical condition

Argininosuccinic aciduria is an inherited disorder that causes the accumulation of argininosuccinic acid in the blood and urine. Some patients may also have an elevation of ammonia, a toxic chemical, which can affect the nervous system. Argininosuccinic aciduria may become evident in the first few days of life because of high blood ammonia, or later in life presenting with "sparse" or "brittle" hair, developmental delay, and tremors.

<span class="mw-page-title-main">Argininosuccinate lyase</span> Mammalian protein found in Homo sapiens

The enzyme argininosuccinate lyase catalyzes the reversible breakdown of argininosuccinate:

<span class="mw-page-title-main">Methylmalonyl-CoA mutase deficiency</span> Medical condition

Methylmalonyl-CoA mutase is a mitochondrial homodimer apoenzyme that focuses on the catalysis of methylmalonyl CoA to succinyl CoA. The enzyme is bound to adenosylcobalamin, a hormonal derivative of vitamin B12 in order to function. Methylmalonyl-CoA mutase deficiency is caused by genetic defect in the MUT gene responsible for encoding the enzyme. Deficiency in this enzyme accounts for 60% of the cases of methylmalonic acidemia.

<span class="mw-page-title-main">N-Acetylglutamate synthase deficiency</span> Medical condition

N-Acetylglutamate synthase deficiency is an autosomal recessive urea cycle disorder.

Carbamoyl phosphate synthetase I deficiency is an autosomal recessive metabolic disorder that causes ammonia to accumulate in the blood due to a lack of the enzyme carbamoyl phosphate synthetase I. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

<span class="mw-page-title-main">Ornithine translocase deficiency</span> Medical condition

Ornithine translocase deficiency, also called hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, is a rare autosomal recessive urea cycle disorder affecting the enzyme ornithine translocase, which causes ammonia to accumulate in the blood, a condition called hyperammonemia.

<span class="mw-page-title-main">Hyperphenylalaninemia</span> Medical condition

Hyperphenylalaninemia is a medical condition characterized by mildly or strongly elevated concentrations of the amino acid phenylalanine in the blood. Phenylketonuria (PKU) can result in severe hyperphenylalaninemia. Phenylalanine concentrations ([phe]) are routinely screened in newborns by the neonatal heel prick, which takes a few drops of blood from the heel of the infant. Standard [phe] concentrations in unaffected persons are about 60µM: [phe] concentrations in persons with untreated phenylketonuria may be many times that, which indicate that the child is at risk for severe intellectual disability. Phenylketonuria is classed as an autosomal recessive condition: in heterozygous form, [phe] shows a moderate elevation, perhaps two-fold over that of unaffected homozygotes, which is classified as hyperphenylalaninemia.

<span class="mw-page-title-main">Argininemia</span> Medical condition

Argininemia is an autosomal recessive urea cycle disorder where a deficiency of the enzyme arginase causes a buildup of arginine and ammonia in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high; the nervous system is especially sensitive to the effects of excess ammonia.

<span class="mw-page-title-main">Ornithine aminotransferase deficiency</span> Medical condition

Ornithine aminotransferase deficiency is an inborn error of ornithine metabolism, caused by decreased activity of the enzyme ornithine aminotransferase. Biochemically, it can be detected by elevated levels of ornithine in the blood. Clinically, it presents initially with poor night vision, which slowly progresses to total blindness. It is believed to be inherited in an autosomal recessive manner. Approximately 200 known cases have been reported in the literature. The incidence is highest in Finland, estimated at 1:50,000.

<span class="mw-page-title-main">Citrullinemia type I</span> Medical condition

Citrullinemia type I (CTLN1), also known as arginosuccinate synthetase deficiency, is a rare disease caused by a deficiency in argininosuccinate synthetase, an enzyme involved in excreting excess nitrogen from the body. There are mild and severe forms of the disease, which is one of the urea cycle disorders.

References

  1. 1 2 Stojanovic, Vesna D.; Doronjski, Aleksandra R.; Barisic, Nenad; Kovacevic, Branka B.; Pavlovic, Vesna S. (2010). "A case of transient hyperammonemia in the newborn transient neonatal hyperammonemia". Journal of Maternal-Fetal and Neonatal Medicine. 23 (4): 347–50. doi:10.3109/14767050903168457. PMID   19658037. S2CID   2493406.
  2. 1 2 Chung, MY; Chen, CC; Huang, LT; Ko, TY; Lin, YJ (2005). "Transient hyperammonemia in a neonate". Acta Paediatrica Taiwanica. 46 (2): 94–6. PMID   16302587.
  3. 1 2 3 4 5 6 7 Crisan, E. "Hyperammonemia". Medscape. Retrieved November 2, 2012.
  4. 1 2 3 4 Roth, K.S. "Genetics of Hyperammonemia". Medscape. Retrieved November 12, 2012.
  5. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Krishnan, L.; Diwakar, K.K.; Patil, P.; Bhaskaranand, N. (1996). "Transient Hyperammonemia of Newborn". The Indian Journal of Pediatrics. 63 (1): 113–116. doi:10.1007/bf02823880. PMID   10829975. S2CID   41551095.
  6. 1 2 3 4 5 6 7 Hudak, M.L.; Jones, M.D.; Brusilow, S.W. (1985). "Differentiation of transient hyperammonemia of the newborn". Journal of Pediatrics. 107 (5): 712–719. doi:10.1016/s0022-3476(85)80398-x. PMID   4056969.
  7. ↑ Ballard RA, Vinocur B, Reyocur B, Reynolds JW et al. Transient hyperammonemia of the preterm infant. N Engl J ed 1978; 299 : 920-925.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.