Managing Emergency Crises and Advanced Care

When a person with HHH syndrome experiences a metabolic crisis, their ammonia levels can rise to toxic heights very quickly. This is a medical emergency that requires specialized hospital care to protect the brain from swelling (cerebral edema) and permanent injury ^[1][2]. The goal of acute management is to stop the body from producing more ammonia and to flush out what is already there ^[3].

Immediate Hospital Interventions

Upon arrival at the nearest emergency department, the medical team will follow a specific metabolic emergency protocol. You should always have a copy of your personal Emergency Letter to give to the doctors immediately, and they must consult your metabolic specialist without delay.

• Halting Protein Intake: The first step is typically a clinician-directed, time-limited pause on “natural” protein (food or formula containing protein) to cut off the source of ammonia ^[3]. Note: Families should not improvise prolonged protein fasting at home; withholding protein for too long worsens catabolism and nutritional deficiency.
• Preventing Catabolism: To keep the body from breaking down its own muscle for energy (which releases more ammonia), doctors provide high-calorie fluids through an IV. This typically includes IV Dextrose (sugar) and, in some cases, IV Lipids (fats) to ensure the patient is receiving enough “eucaloric” support ^[4][3].
• IV Ammonia Scavengers: Medications like IV Sodium Benzoate or Sodium Phenylacetate are given to create an “emergency exit” for nitrogen, allowing the body to bypass the impaired urea cycle and pee out waste ^[5][2]. Never attempt to self-dose these IV medications.
• IV Arginine: This amino acid is often given intravenously to keep the remaining parts of the urea cycle moving as much as possible ^[2].

Advanced Ammonia Removal: Dialysis

If medications and IV fluids are not lowering the ammonia levels quickly enough, or if the patient is showing signs of deep confusion, seizures, or coma, doctors must use advanced technology to “clean” the blood ^[3][6].

• Hemodialysis: This is the fastest way to remove ammonia from the bloodstream ^[7].
• CRRT (Continuous Renal Replacement Therapy): This is a slower, gentler form of dialysis used in intensive care units (ICUs) for patients who may be too unstable for standard hemodialysis ^[1][8].
• When It’s Needed: The decision to dialyze depends on age, absolute level, rate of rise, and neurologic findings. While many experts consider starting dialysis if ammonia is rising rapidly despite medical treatment ^[9][10][11], patients should never wait for a specific threshold number to seek care.

Liver Transplantation in HHH

For some carefully selected patients, HHH syndrome remains difficult to control even with a strict diet and medications. In these cases, a liver transplant at an experienced center may be considered ^[3][12].

• Metabolic Improvement: A successful transplant essentially provides donor liver cells with functioning transport and urea-cycle machinery. After a transplant, ammonia and amino acid levels usually normalize, and some patients can significantly loosen dietary restrictions ^[13][2].
• Neurological Impact: A transplant can prevent future brain injury and often improves quality of life, mood, and some motor skills like walking ^[13]. However, it is important to understand that a transplant cannot reverse neurological damage (like intellectual disability or existing spasticity) that occurred before the surgery ^[2][13]. It also does not correct the defect in other, non-liver tissues.
• Timing and Risks: Transplantation carries major risks, including rejection, severe infection, and lifelong immunosuppression. Many specialists recommend considering a transplant before irreversible neurological injury occurs, especially if metabolic crises are frequent ^[13].

Monitoring for Rebound

Once a crisis begins to resolve, the team will monitor ammonia levels very closely. It is common for ammonia to “rebound” (rise again) shortly after dialysis stops or as the body begins to process stored waste ^[14]. Treatment continues until levels are stable and the patient can safely begin a clinician-guided reintroduction of protein ^[15].