Saved in:
| Main Authors: | , |
|---|---|
| Format: | Artículo Open Access |
| Published: |
Wiley
2025
|
| Subjects: | |
| Online Access: | https://onlinelibrary.wiley.com/doi/10.1111/ped.70121 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1867021158457540608 |
|---|---|
| author | Jun Kido Kimitoshi Nakamura |
| author_facet | Jun Kido Kimitoshi Nakamura Jun Kido Kimitoshi Nakamura |
| collection | Wiley Open Access |
| contents | Hyperammonemia in urea cycle disorders: A toxic metabolite for the brain Jun Kido Kimitoshi Nakamura Pediatrics International Abstract Ammonia can easily cross the blood–brain barrier in its non‐ionized form, leading to significant accumulation in the brain during severe hyperammonemia. Excess ammonia is highly toxic to the brain and can cause neurological dysfunctions, such as tremors, ataxia, seizures, coma, and even death. Hyperammonemia is often the primary manifestation of urea cycle disorders (UCDs), a group of inherited metabolic disorders characterized by impaired nitrogen detoxification due to dysfunctions in urea cycle‐related enzymes and transporters. Patients with complete deficiencies of urea cycle enzymes typically present with lethargy, hypothermia, anorexia, seizures, abnormal respiratory patterns (hyperventilation or hypoventilation), neurologic posturing, and coma, along with hyperammonemia within a few days after birth. This condition, classified as the neonatal‐onset type, frequently results in severe hyperammonemic encephalopathy (≥600 μg/dL [360 μmol/L]) at onset. Hyperammonemia with blood ammonia levels of 600 μg/dL (360 μmol/L) or higher causes significant brain damage. Therefore, at this threshold, hemodialysis is indicated to rapidly remove ammonia and mitigate its harmful effects on the brain. However, even when neonatal‐onset UCD patients undergo a combination of hemodialysis and liver transplantation at the onset of severe hyperammonemia (≥600 μg/dL [360 μmol/L]), the neuroprotective effects remain limited. This review aims to describe the pathophysiology of hyperammonemia and UCDs, the impact of hyperammonemia on the brain in UCDs, the role of current therapeutic strategies, and the challenges associated with future treatments for UCDs. 10.1111/ped.70121 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1111/ped.70121 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_ped_70121 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Hyperammonemia in urea cycle disorders: A toxic metabolite for the brain Jun Kido Kimitoshi Nakamura Pediatrics International Hyperammonemia in urea cycle disorders: A toxic metabolite for the brain Jun Kido Kimitoshi Nakamura Pediatrics International Abstract Ammonia can easily cross the blood–brain barrier in its non‐ionized form, leading to significant accumulation in the brain during severe hyperammonemia. Excess ammonia is highly toxic to the brain and can cause neurological dysfunctions, such as tremors, ataxia, seizures, coma, and even death. Hyperammonemia is often the primary manifestation of urea cycle disorders (UCDs), a group of inherited metabolic disorders characterized by impaired nitrogen detoxification due to dysfunctions in urea cycle‐related enzymes and transporters. Patients with complete deficiencies of urea cycle enzymes typically present with lethargy, hypothermia, anorexia, seizures, abnormal respiratory patterns (hyperventilation or hypoventilation), neurologic posturing, and coma, along with hyperammonemia within a few days after birth. This condition, classified as the neonatal‐onset type, frequently results in severe hyperammonemic encephalopathy (≥600 μg/dL [360 μmol/L]) at onset. Hyperammonemia with blood ammonia levels of 600 μg/dL (360 μmol/L) or higher causes significant brain damage. Therefore, at this threshold, hemodialysis is indicated to rapidly remove ammonia and mitigate its harmful effects on the brain. However, even when neonatal‐onset UCD patients undergo a combination of hemodialysis and liver transplantation at the onset of severe hyperammonemia (≥600 μg/dL [360 μmol/L]), the neuroprotective effects remain limited. This review aims to describe the pathophysiology of hyperammonemia and UCDs, the impact of hyperammonemia on the brain in UCDs, the role of current therapeutic strategies, and the challenges associated with future treatments for UCDs. 10.1111/ped.70121 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Hyperammonemia in urea cycle disorders: A toxic metabolite for the brain |
| topic | Pediatrics International |
| url | https://onlinelibrary.wiley.com/doi/10.1111/ped.70121 |