Tyrosinemia - Revision history

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Ostermayer: Created page with "Tyrosinemia refers to a group of inherited disorders of tyrosine metabolism. '''Tyrosinemia type 1 (HT1)''' is the most severe and EM-relevant form, caused by deficiency of fumarylacetoacetate hydrolase (FAH), leading to accumulation of toxic metabolites that cause '''acute liver failure''', '''Fanconi syndrome''', '''porphyria-like neurologic crises''', and '''hepatocellular carcinoma'''.Tyrosinemia Type I. ''GeneRevie..."

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Created page with "Tyrosinemia refers to a group of inherited disorders of tyrosine metabolism. '''Tyrosinemia type 1 (HT1)''' is the most severe and EM-relevant form, caused by deficiency of fumarylacetoacetate hydrolase (FAH), leading to accumulation of toxic metabolites that cause '''acute liver failure''', '''Fanconi syndrome''', '''porphyria-like neurologic crises''', and '''hepatocellular carcinoma'''.<ref name="GeneReviews">Tyrosinemia Type I. ''GeneRevie..."

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Tyrosinemia refers to a group of inherited disorders of tyrosine metabolism. '''Tyrosinemia type 1 (HT1)''' is the most severe and EM-relevant form, caused by deficiency of fumarylacetoacetate hydrolase (FAH), leading to accumulation of toxic metabolites that cause '''[[Acute liver failure|acute liver failure]]''', '''[[Fanconi syndrome]]''', '''porphyria-like neurologic crises''', and '''hepatocellular carcinoma'''.<ref name="GeneReviews">Tyrosinemia Type I. ''GeneReviews''. NCBI. 2025.</ref> Emergency physicians may encounter HT1 patients presenting with '''fulminant hepatic failure in infancy''', '''unexplained coagulopathy''', '''neurologic crises mimicking [[Acute intermittent porphyria|porphyria]] or [[Guillain-Barré syndrome]]''', or '''metabolic decompensation from missed nitisinone doses'''.<ref name="Medscape">Tyrosinemia. ''Medscape''. 2025.</ref>

==Background==
*Autosomal recessive; incidence ~1 in 100,000 births worldwide; much higher in Saguenay-Lac-Saint-Jean region of Quebec (1 in 1,850)<ref name="GeneReviews"/>
*Three types exist; '''type 1 is the focus of this page''' as it is by far the most EM-relevant:

{| class="wikitable"
|-
! Type !! Enzyme deficiency !! Key features
|-
| '''Type 1 (hepatorenal)''' || Fumarylacetoacetate hydrolase (FAH) || Liver failure, Fanconi syndrome, neurologic crises, HCC risk; '''life-threatening'''
|-
| Type 2 (oculocutaneous) || Tyrosine aminotransferase || Painful palmoplantar keratosis, herpetiform corneal ulcers; no liver disease
|-
| Type 3 || 4-hydroxyphenylpyruvate dioxygenase || Mild; intellectual disability; extremely rare
|}

===Mechanism of toxicity (Type 1)===
*FAH deficiency → accumulation of '''fumarylacetoacetate (FAA)''', '''maleylacetoacetate (MAA)''', and '''succinylacetone (SA)''' — all are directly cytotoxic<ref name="GeneReviews"/>
*SA is a '''mitochondrial toxin''' → proximal tubule dysfunction → '''[[Fanconi syndrome]]'''
*SA '''inhibits porphobilinogen synthase''' (δ-aminolevulinic acid dehydratase) → accumulation of '''δ-aminolevulinic acid (δ-ALA)''' → '''porphyria-like neurologic crises''' (identical mechanism to [[Lead poisoning|lead poisoning]] and [[Acute intermittent porphyria|acute intermittent porphyria]])<ref name="Medscape"/>
*FAA/MAA cause direct hepatocellular damage → cirrhosis, liver failure, hepatocellular carcinoma
*'''Nitisinone (NTBC)''' blocks the pathway upstream of FAH, preventing formation of all toxic metabolites — this transforms HT1 from a fatal disease into a manageable chronic condition<ref name="deLatVL2013">de Laet C, et al. Recommendations for the management of tyrosinaemia type 1. ''Orphanet J Rare Dis''. 2013;8:8. doi:10.1186/1750-1172-8-8</ref>

==Clinical features==
===Presentations the EM physician will encounter===

====Acute liver failure (infants <6 months) — the classic presentation====
*Often the '''first presentation''' of undiagnosed HT1
*Jaundice, hepatomegaly
*'''Severe coagulopathy''' (disproportionate to degree of jaundice — INR may be markedly elevated with only mild transaminase elevation; this pattern is characteristic)<ref name="GeneReviews"/>
*Ascites
*Hypoglycemia
*Bleeding (GI hemorrhage, oozing from venipuncture sites)
*Sepsis (increased susceptibility)
*'''Boiled cabbage odor''' to urine/sweat (from methionine accumulation; classic but not always present)<ref name="Medscape"/>
*Failure to thrive, vomiting, diarrhea, fever
*May progress rapidly to multiorgan failure and death

====Porphyria-like neurologic crisis — the most dangerous acute emergency====
*Occurs in '''untreated''' patients or patients who '''stop or miss nitisinone doses'''<ref name="NTBC_Crisis">Tyrosinemia Type I and Reversible Neurogenic Crisis After a One-Month Interruption of Nitisinone. ''J Pediatr Res''. 2018.</ref>
*Episodic, lasting '''1-7 days'''; often triggered by intercurrent infection
*'''Severe abdominal pain''' (may mimic acute abdomen/surgical emergency)
*Painful paresthesias, peripheral neuropathy (ascending; may mimic [[Guillain-Barré syndrome]])
*Progressive '''muscle weakness''' including respiratory muscles → '''respiratory failure requiring mechanical ventilation'''<ref name="GeneReviews"/>
*Self-injurious behavior (in response to extreme pain)
*Seizures
*'''Hypertension''' (often marked)
*'''Hyponatremia''' (SIADH-like)
*Altered mental status, irritability, agitation
*'''Can be fatal''' from respiratory arrest if unrecognized
*Mechanism identical to acute porphyria: elevated δ-ALA from SA inhibition of porphobilinogen synthase

====Chronic/subacute presentation (>6 months)====
*Hepatosplenomegaly, failure to thrive
*'''[[Fanconi syndrome]]:''' polyuria, polydipsia, metabolic acidosis, hypophosphatemia, hypokalemia, glycosuria, aminoaciduria
*'''Rickets''' (from phosphate wasting + impaired vitamin D activation)
*Progressive chronic kidney disease
*'''Hypertrophic cardiomyopathy''' (reported in up to 30%)<ref name="Medscape"/>

====Known HT1 patient with metabolic decompensation====
*'''Missed nitisinone doses''' → rapid reaccumulation of toxic metabolites → acute liver dysfunction, neurologic crisis, or both<ref name="NTBC_Crisis"/>
*Intercurrent illness → catabolic state → increased tyrosine turnover → metabolic decompensation
*Noncompliance (especially in adolescents)

==Differential diagnosis==
===Infant with acute liver failure and coagulopathy===
*[[Neonatal hepatitis]] (other causes)
*[[Galactosemia]]
*[[Hereditary fructose intolerance]]
*[[Neonatal hemochromatosis]]
*[[Gestational alloimmune liver disease]]
*Viral hepatitis (HSV, enterovirus, adenovirus)
*[[Sepsis]]
*[[Biliary atresia]]
*[[Acetaminophen toxicity]]

===Porphyria-like neurologic crisis===
*[[Acute intermittent porphyria]]
*[[Lead poisoning]]
*[[Guillain-Barré syndrome]]
*[[Abdominal pain (peds)]] (surgical causes)
*[[Intussusception]]

===[[Fanconi syndrome]] (other causes)===
*[[Cystinosis]] (most common inherited cause)
*Drug-induced (tenofovir, ifosfamide, valproic acid)
*[[Wilson disease]]

==Evaluation==
===EM workup===
*'''Hepatic function panel:''' AST/ALT may be only mildly elevated despite severe synthetic dysfunction (a characteristic discrepancy); bilirubin elevated
*'''Coagulation studies:''' '''INR/PT markedly elevated''' — often the most striking lab abnormality; disproportionate to transaminases<ref name="GeneReviews"/>
*'''Blood glucose:''' hypoglycemia (hepatic failure)
*'''BMP:''' hypokalemia, hypophosphatemia, low bicarbonate (Fanconi/RTA), hyponatremia (in neurologic crises)
*'''CBC:''' anemia, thrombocytopenia (from liver failure/hypersplenism)
*'''AFP (alpha-fetoprotein):''' '''markedly elevated''' (often >100,000 ng/mL) — this is a key diagnostic clue; AFP in HT1 is among the highest of any condition<ref name="GeneReviews"/>
*'''Ammonia:''' elevated in severe hepatic failure
*'''Lactate:''' elevated if tissue hypoperfusion or metabolic crisis
*'''ABG/VBG:''' metabolic acidosis (from Fanconi syndrome and/or hepatic failure)
*'''Urinalysis:''' glycosuria (normal glucose), aminoaciduria, phosphaturia (Fanconi pattern)
*'''ECG/echocardiography:''' if cardiomyopathy suspected

===Diagnostic confirmation (arrange via specialist; not ED tests)===
*'''Urine/blood succinylacetone:''' '''pathognomonic''' for HT1; the definitive screening marker<ref name="GeneReviews"/>
*Elevated plasma tyrosine, methionine, phenylalanine
*Elevated urinary δ-aminolevulinic acid (during neurologic crises)
*'''FAH gene mutation analysis''' (confirmatory)

===When to suspect HT1 in the ED===
*Infant with '''liver failure + coagulopathy out of proportion to transaminases + very high AFP'''
*Infant/child with '''Fanconi syndrome + liver disease''' (most causes of Fanconi syndrome spare the liver; HT1 affects both)
*Child with '''porphyria-like crisis''' (abdominal pain + neuropathy + hypertension + hyponatremia) — porphyria is extremely rare in children; consider HT1
*'''Boiled cabbage''' odor
*Known HT1 patient who has missed nitisinone doses and presents with acute symptoms

==Management==
===Acute liver failure===
*Manage per standard '''[[Acute liver failure]]''' protocols:
**IV fluids, correct hypoglycemia (D10W infusion)
**FFP, cryoprecipitate, vitamin K for coagulopathy/active bleeding
**Treat/prevent [[Hepatic encephalopathy]] (lactulose, rifaximin)
**Broad-spectrum antibiotics if sepsis suspected
**Monitor ammonia, electrolytes, glucose frequently
*'''Start nitisinone (NTBC) immediately''' if HT1 is suspected or confirmed — '''do not wait for confirmatory testing'''<ref name="deLatVL2013"/>
**Dose: 1-2 mg/kg/day orally (can be given via NG tube)
**May show clinical improvement within hours to days
**If liver fails to respond to nitisinone within 1 week → '''liver transplant referral'''<ref name="Orphanet">Tyrosinemia type 1. ''Orphanet''. 2024.</ref>
*'''Early contact with metabolic/hepatology center''' — these patients may need emergent liver transplant

===Neurologic crisis===
*'''Restart or increase nitisinone immediately''' if doses were missed — this is the definitive treatment<ref name="NTBC_Crisis"/>
*'''Monitor respiratory function closely''' — progressive neuropathy can cause respiratory failure requiring '''intubation and mechanical ventilation'''<ref name="GeneReviews"/>
*'''Pain management:''' opioids may be required for severe pain; avoid hepatotoxic agents
*'''Seizure management:''' [[Benzodiazepines|benzodiazepines]] first-line
*'''Hypertension management:''' may require antihypertensives
*'''Correct hyponatremia''' carefully (risk of osmotic demyelination with rapid correction)
*'''Glucose infusion''' (10% dextrose) — high-calorie IV fluids reduce protein catabolism and tyrosine turnover
*'''Do NOT give hemin''' (used in acute porphyria) — not indicated and not effective in HT1 neurologic crises; the mechanism involves δ-ALA accumulation from SA, not a deficiency in heme synthesis pathway

===Fanconi syndrome management===
*Potassium, phosphate, bicarbonate supplementation (see [[Fanconi syndrome]])
*IV fluids for dehydration
*Vitamin D (calcitriol)

===Medication safety===
*'''Do NOT discontinue nitisinone''' — interruption can precipitate life-threatening liver failure or neurologic crisis within days to weeks<ref name="NTBC_Crisis"/>
*If the patient cannot take oral nitisinone (vomiting, intubation), contact the metabolic team immediately for guidance
*'''Avoid hepatotoxic medications''' (acetaminophen, hepatically metabolized drugs) in patients with liver disease
*Maintain '''low-tyrosine/low-phenylalanine diet''' — if the patient is NPO, provide IV dextrose to reduce catabolism; consult metabolic dietitian

==Disposition==
*'''Acute liver failure:''' ICU admission; early contact with liver transplant center and metabolic specialist
*'''Neurologic crisis:''' ICU admission (risk of respiratory failure); continuous monitoring; restart nitisinone
*'''New diagnosis suspected (infant with liver failure + high AFP + coagulopathy):''' admit; start nitisinone while awaiting confirmatory tests; metabolic/genetics and hepatology consultation
*'''Known HT1 patient with intercurrent illness:''' low threshold for admission; monitor liver function, electrolytes, glucose; ensure nitisinone is continued; IV dextrose to reduce catabolism
*'''Stable known HT1 patient with mild illness:''' may consider discharge with close metabolic team follow-up if PO tolerant, nitisinone continued, and caregiver reliable
*Notify the patient's '''metabolic specialist''' of all ED visits

==See Also==
*[[Fanconi syndrome]]
*[[Acute liver failure]]
*[[Acute intermittent porphyria]]
*[[Lead poisoning]]
*[[Cystinosis]]
*[[Galactosemia]]
*[[Wilson disease]]
*[[Hepatocellular carcinoma]]
*[[Guillain-Barré syndrome]]

==External Links==
*[https://www.ncbi.nlm.nih.gov/books/NBK1515/ GeneReviews — Tyrosinemia Type I]
*[https://emedicine.medscape.com/article/949816-overview Medscape — Tyrosinemia]
*[https://pmc.ncbi.nlm.nih.gov/articles/PMC3558375/ Orphanet J Rare Dis — Recommendations for the management of tyrosinaemia type 1 (2013)]
*[https://rarediseases.org/rare-diseases/tyrosinemia-type-1/ NORD — Tyrosinemia Type 1]
*[https://www.orpha.net/en/disease/detail/882 Orphanet — Tyrosinemia type 1]

==References==
<references/>

[[Category:Pediatrics]]
[[Category:GI]]

← Older revision		Revision as of 09:30, 22 March 2026
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	*Tyrosinemia type 1 (HT1) is the most severe and EM-relevant form, caused by deficiency of fumarylacetoacetate hydrolase (FAH), leading to accumulation of toxic metabolites that cause [[Acute liver failure\|acute liver failure]], [[Fanconi syndrome]], porphyria-like neurologic crises, and hepatocellular carcinoma.<ref name="GeneReviews">Tyrosinemia Type I. ''GeneReviews''. NCBI. 2025.</ref> Emergency physicians may encounter HT1 patients presenting with fulminant hepatic failure in infancy, unexplained coagulopathy, neurologic crises mimicking [[Acute intermittent porphyria\|porphyria]] or [[Guillain-Barré syndrome]], or metabolic decompensation from missed nitisinone doses.<ref name="Medscape">Tyrosinemia. ''Medscape''. 2025.</ref>		*Tyrosinemia type 1 (HT1) is the most severe and EM-relevant form, caused by deficiency of fumarylacetoacetate hydrolase (FAH), leading to accumulation of toxic metabolites that cause [[Acute liver failure\|acute liver failure]], [[Fanconi syndrome]], porphyria-like neurologic crises, and hepatocellular carcinoma.<ref name="GeneReviews">Tyrosinemia Type I. ''GeneReviews''. NCBI. 2025.</ref> Emergency physicians may encounter HT1 patients presenting with fulminant hepatic failure in infancy, unexplained coagulopathy, neurologic crises mimicking [[Acute intermittent porphyria\|porphyria]] or [[Guillain-Barré syndrome]], or metabolic decompensation from missed nitisinone doses.<ref name="Medscape">Tyrosinemia. ''Medscape''. 2025.</ref>
	*Autosomal recessive; incidence ~1 in 100,000 births worldwide; much higher in Saguenay-Lac-Saint-Jean region of Quebec (1 in 1,850)<ref name="GeneReviews"/>		*Autosomal recessive; incidence ~1 in 100,000 births worldwide; much higher in Saguenay-Lac-Saint-Jean region of Quebec (1 in 1,850)<ref name="GeneReviews"/>
	*Three types exist; ~~'''~~type 1 is the focus of this page~~'''~~ as it is by far the most EM-relevant:		*Three types exist; type 1 is the focus of this page as it is by far the most EM-relevant:

	{\| class="wikitable"		{\| class="wikitable"
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	===Mechanism of toxicity (Type 1)===		===Mechanism of toxicity (Type 1)===
	*FAH deficiency → accumulation of ~~'''~~fumarylacetoacetate (FAA)~~'''~~, ~~'''~~maleylacetoacetate (MAA)~~'''~~, and ~~'''~~succinylacetone (SA)~~'''~~ — all are directly cytotoxic<ref name="GeneReviews"/>		*FAH deficiency → accumulation of fumarylacetoacetate (FAA), maleylacetoacetate (MAA), and succinylacetone (SA) — all are directly cytotoxic<ref name="GeneReviews"/>
	*SA is a ~~'''~~mitochondrial toxin~~'''~~ → proximal tubule dysfunction → ~~'''~~[[Fanconi syndrome]]~~'''~~		*SA is a mitochondrial toxin → proximal tubule dysfunction → [[Fanconi syndrome]]
	*SA ~~'''~~inhibits porphobilinogen synthase~~'''~~ (δ-aminolevulinic acid dehydratase) → accumulation of ~~'''~~δ-aminolevulinic acid (δ-ALA)~~'''~~ → ~~'''~~porphyria-like neurologic crises~~'''~~ (identical mechanism to [[Lead poisoning\|lead poisoning]] and [[Acute intermittent porphyria\|acute intermittent porphyria]])<ref name="Medscape"/>		*SA inhibits porphobilinogen synthase (δ-aminolevulinic acid dehydratase) → accumulation of δ-aminolevulinic acid (δ-ALA) → porphyria-like neurologic crises (identical mechanism to [[Lead poisoning\|lead poisoning]] and [[Acute intermittent porphyria\|acute intermittent porphyria]])<ref name="Medscape"/>
	*FAA/MAA cause direct hepatocellular damage → cirrhosis, liver failure, hepatocellular carcinoma		*FAA/MAA cause direct hepatocellular damage → cirrhosis, liver failure, hepatocellular carcinoma
	* Nitisinone (NTBC) blocks the pathway upstream of FAH, preventing formation of all toxic metabolites — this transforms HT1 from a fatal disease into a manageable chronic condition<ref name="deLatVL2013">de Laet C, et al. Recommendations for the management of tyrosinaemia type 1. ''Orphanet J Rare Dis''. 2013;8:8. doi:10.1186/1750-1172-8-8</ref>		* Nitisinone (NTBC) blocks the pathway upstream of FAH, preventing formation of all toxic metabolites — this transforms HT1 from a fatal disease into a manageable chronic condition<ref name="deLatVL2013">de Laet C, et al. Recommendations for the management of tyrosinaemia type 1. ''Orphanet J Rare Dis''. 2013;8:8. doi:10.1186/1750-1172-8-8</ref>
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	====Acute liver failure (infants <6 months) — the classic presentation====		====Acute liver failure (infants <6 months) — the classic presentation====
	*Often the ~~'''~~first presentation~~'''~~ of undiagnosed HT1		*Often the first presentation of undiagnosed HT1
	*Jaundice, hepatomegaly		*Jaundice, hepatomegaly
	* Severe coagulopathy (disproportionate to degree of jaundice — INR may be markedly elevated with only mild transaminase elevation; this pattern is characteristic)<ref name="GeneReviews"/>		* Severe coagulopathy (disproportionate to degree of jaundice — INR may be markedly elevated with only mild transaminase elevation; this pattern is characteristic)<ref name="GeneReviews"/>
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	====Porphyria-like neurologic crisis — the most dangerous acute emergency====		====Porphyria-like neurologic crisis — the most dangerous acute emergency====
	*Occurs in ~~'''~~untreated~~'''~~ patients or patients who ~~'''~~stop or miss nitisinone doses~~'''~~<ref name="NTBC_Crisis">Tyrosinemia Type I and Reversible Neurogenic Crisis After a One-Month Interruption of Nitisinone. ''J Pediatr Res''. 2018.</ref>		*Occurs in untreated patients or patients who stop or miss nitisinone doses<ref name="NTBC_Crisis">Tyrosinemia Type I and Reversible Neurogenic Crisis After a One-Month Interruption of Nitisinone. ''J Pediatr Res''. 2018.</ref>
	*Episodic, lasting ~~'''~~1-7 days~~'''~~; often triggered by intercurrent infection		*Episodic, lasting 1-7 days; often triggered by intercurrent infection
	* Severe abdominal pain (may mimic acute abdomen/surgical emergency)		* Severe abdominal pain (may mimic acute abdomen/surgical emergency)
	*Painful paresthesias, peripheral neuropathy (ascending; may mimic [[Guillain-Barré syndrome]])		*Painful paresthesias, peripheral neuropathy (ascending; may mimic [[Guillain-Barré syndrome]])
	*Progressive ~~'''~~muscle weakness~~'''~~ including respiratory muscles → ~~'''~~respiratory failure requiring mechanical ventilation~~'''~~<ref name="GeneReviews"/>		*Progressive muscle weakness including respiratory muscles → respiratory failure requiring mechanical ventilation<ref name="GeneReviews"/>
	*Self-injurious behavior (in response to extreme pain)		*Self-injurious behavior (in response to extreme pain)
	*Seizures		*Seizures
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	===EM workup===		===EM workup===
	* Hepatic function panel: AST/ALT may be only mildly elevated despite severe synthetic dysfunction (a characteristic discrepancy); bilirubin elevated		* Hepatic function panel: AST/ALT may be only mildly elevated despite severe synthetic dysfunction (a characteristic discrepancy); bilirubin elevated
	* Coagulation studies: ~~'''~~INR/PT markedly elevated~~'''~~ — often the most striking lab abnormality; disproportionate to transaminases<ref name="GeneReviews"/>		* Coagulation studies: INR/PT markedly elevated — often the most striking lab abnormality; disproportionate to transaminases<ref name="GeneReviews"/>
	* Blood glucose: hypoglycemia (hepatic failure)		* Blood glucose: hypoglycemia (hepatic failure)
	* BMP: hypokalemia, hypophosphatemia, low bicarbonate (Fanconi/RTA), hyponatremia (in neurologic crises)		* BMP: hypokalemia, hypophosphatemia, low bicarbonate (Fanconi/RTA), hyponatremia (in neurologic crises)
	* CBC: anemia, thrombocytopenia (from liver failure/hypersplenism)		* CBC: anemia, thrombocytopenia (from liver failure/hypersplenism)
	* AFP (alpha-fetoprotein): ~~'''~~markedly elevated~~'''~~ (often >100,000 ng/mL) — this is a key diagnostic clue; AFP in HT1 is among the highest of any condition<ref name="GeneReviews"/>		* AFP (alpha-fetoprotein): markedly elevated (often >100,000 ng/mL) — this is a key diagnostic clue; AFP in HT1 is among the highest of any condition<ref name="GeneReviews"/>
	* Ammonia: elevated in severe hepatic failure		* Ammonia: elevated in severe hepatic failure
	* Lactate: elevated if tissue hypoperfusion or metabolic crisis		* Lactate: elevated if tissue hypoperfusion or metabolic crisis
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	===Diagnostic confirmation (arrange via specialist; not ED tests)===		===Diagnostic confirmation (arrange via specialist; not ED tests)===
	* Urine/blood succinylacetone: ~~'''~~pathognomonic~~'''~~ for HT1; the definitive screening marker<ref name="GeneReviews"/>		* Urine/blood succinylacetone: pathognomonic for HT1; the definitive screening marker<ref name="GeneReviews"/>
	*Elevated plasma tyrosine, methionine, phenylalanine		*Elevated plasma tyrosine, methionine, phenylalanine
	*Elevated urinary δ-aminolevulinic acid (during neurologic crises)		*Elevated urinary δ-aminolevulinic acid (during neurologic crises)
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	===When to suspect HT1 in the ED===		===When to suspect HT1 in the ED===
	*Infant with ~~'''~~liver failure + coagulopathy out of proportion to transaminases + very high AFP~~'''~~		*Infant with liver failure + coagulopathy out of proportion to transaminases + very high AFP
	*Infant/child with ~~'''~~Fanconi syndrome + liver disease~~'''~~ (most causes of Fanconi syndrome spare the liver; HT1 affects both)		*Infant/child with Fanconi syndrome + liver disease (most causes of Fanconi syndrome spare the liver; HT1 affects both)
	*Child with ~~'''~~porphyria-like crisis~~'''~~ (abdominal pain + neuropathy + hypertension + hyponatremia) — porphyria is extremely rare in children; consider HT1		*Child with porphyria-like crisis (abdominal pain + neuropathy + hypertension + hyponatremia) — porphyria is extremely rare in children; consider HT1
	* Boiled cabbage odor		* Boiled cabbage odor
	*Known HT1 patient who has missed nitisinone doses and presents with acute symptoms		*Known HT1 patient who has missed nitisinone doses and presents with acute symptoms
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	==Management==		==Management==
	===Acute liver failure===		===Acute liver failure===
	*Manage per standard ~~'''~~[[Acute liver failure]]~~'''~~ protocols:		*Manage per standard [[Acute liver failure]] protocols:
	**IV fluids, correct hypoglycemia (D10W infusion)		**IV fluids, correct hypoglycemia (D10W infusion)
	**FFP, cryoprecipitate, vitamin K for coagulopathy/active bleeding		**FFP, cryoprecipitate, vitamin K for coagulopathy/active bleeding
Line 126:		Line 126:
	**Dose: 1-2 mg/kg/day orally (can be given via NG tube)		**Dose: 1-2 mg/kg/day orally (can be given via NG tube)
	**May show clinical improvement within hours to days		**May show clinical improvement within hours to days
	**If liver fails to respond to nitisinone within 1 week → ~~'''~~liver transplant referral~~'''~~<ref name="Orphanet">Tyrosinemia type 1. ''Orphanet''. 2024.</ref>		**If liver fails to respond to nitisinone within 1 week → liver transplant referral<ref name="Orphanet">Tyrosinemia type 1. ''Orphanet''. 2024.</ref>
	* Early contact with metabolic/hepatology center — these patients may need emergent liver transplant		* Early contact with metabolic/hepatology center — these patients may need emergent liver transplant

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	*If the patient cannot take oral nitisinone (vomiting, intubation), contact the metabolic team immediately for guidance		*If the patient cannot take oral nitisinone (vomiting, intubation), contact the metabolic team immediately for guidance
	* Avoid hepatotoxic medications (acetaminophen, hepatically metabolized drugs) in patients with liver disease		* Avoid hepatotoxic medications (acetaminophen, hepatically metabolized drugs) in patients with liver disease
	*Maintain ~~'''~~low-tyrosine/low-phenylalanine diet~~'''~~ — if the patient is NPO, provide IV dextrose to reduce catabolism; consult metabolic dietitian		*Maintain low-tyrosine/low-phenylalanine diet — if the patient is NPO, provide IV dextrose to reduce catabolism; consult metabolic dietitian

	==Disposition==		==Disposition==
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	* Known HT1 patient with intercurrent illness: low threshold for admission; monitor liver function, electrolytes, glucose; ensure nitisinone is continued; IV dextrose to reduce catabolism		* Known HT1 patient with intercurrent illness: low threshold for admission; monitor liver function, electrolytes, glucose; ensure nitisinone is continued; IV dextrose to reduce catabolism
	* Stable known HT1 patient with mild illness: may consider discharge with close metabolic team follow-up if PO tolerant, nitisinone continued, and caregiver reliable		* Stable known HT1 patient with mild illness: may consider discharge with close metabolic team follow-up if PO tolerant, nitisinone continued, and caregiver reliable
	*Notify the patient's ~~'''~~metabolic specialist~~'''~~ of all ED visits		*Notify the patient's metabolic specialist of all ED visits

	==See Also==		==See Also==