Hematin therapy for the neurologic crisis of tyrosinemia

Rank, Jeffrey M.; Pascual‐Leone, Álvaro; Payne, William D.; Glock, Michael; Freese, Deborah K.; Sharp, Harvey L.; Bloomer, Joseph R.

doi:10.1016/s0022-3476(05)81867-0

Cited by 31 publications

(13 citation statements)

References 6 publications

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“…In a case of tyrosinemia, neurological crisis was treated with hemin infusion to good effect. 4 The present paper includes a case of lead poisoning in which the symptoms similarly responded to hemin.…”

Section: Introductionmentioning

confidence: 97%

Role of Delta-aminolevulinic Acid in the Symptoms of Acute Porphyria

Bissell

Lai

Meister

et al. 2015

The American Journal of Medicine

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Background Attacks of neuropathic pain, usually abdominal, are characteristic of the acute porphyrias and are accompanied by overproduction of heme-precursor molecules, specifically delta-aminolevulinic acid and porphobilinogen. The basis for the acute symptoms in these diseases has been speculative. Methods We review genetic acute porphyria, hereditary tyrosinemia, and an acquired condition, lead poisoning. All perturb heme synthesis and present with a very similar pain syndrome. Results While each of these conditions has characteristic urine biochemistry, all exhibit excess delta-aminolevulinic acid. Moreover, in all, treatment with hemin reduces delta-aminolevulinic acid and relieves symptoms. In contrast, use of recombinant porphobilinogen deaminase to knock down porphobilinogen in acute porphyria was ineffective. Conclusion There is now convincing evidence that delta-aminolevulinic acid is the cause of pain in the acute porphyrias. The efficacy of hemin infusion is due mainly, if not entirely, to its inhibition of hepatic delta-aminolevulinic acid synthase-1, the enzyme that catalyzes delta-aminolevulinic acid formation. Delta-aminolevulinic acid synthase-1 is a rational target for additional therapies to control symptoms in acute porphyria.

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Section: Introductionmentioning

confidence: 97%

Role of Delta-aminolevulinic Acid in the Symptoms of Acute Porphyria

Bissell

Lai

Meister

et al. 2015

The American Journal of Medicine

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“…Neurologic crisis is usually not associated with deterioration of the usual liver function tests. Urinary levels of δ-aminolevulinic acid (δ-ALA) tend to be higher during crisis secondary to inhibition of RBC δ-ALA hydratase, which is believed to explain such pain crises [152][153][154]. Treatment of the pain crises is mainly through dextrose containing fluids (dextrose 10% with normal saline) at 1.5 to 2 times maintenance rate for age and weight along with analgesics.…”

Section: Neurologic Crisismentioning

confidence: 99%

Disorders of phenylalanine and tyrosine metabolism

Alsharhan

Fıçıcıoğlu

2020

TRD

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This article provides a review of the inborn errors of phenylalanine and tyrosine metabolism including the diagnostic approach, dietary and pharmalogical management and emerging therapies. Hyperphenylalaninaemia results mainly from defects in either phenylalanine hydroxylase (PAH) (resulting in phenylketonuria (PKU)) or the production or recycling of tetrahydrobiopterin (BH 4). Untreated PKU results in irreversible neurocognitive impairment. Five inherited disorders of tyrosine metabolism are known, which include tyrosinemia type I, type II, type III, hawkinsinuria and alkaptonuria. Newborn screening for these disorders has enabled their early detection and decreased the associated morbidity and mortality.

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“…28 The mechanism of neurologic dysfunction may be the same because patients with tyrosinemia respond to the intravenous administration of hematin. 29 These crises have two phases: …”

Section: Diagnosis By Both Characteristic Clinical Picture and Investmentioning

confidence: 99%

Current management options for tyrosinemia

El‐Shabrawi¹,

Kamal²

2013

ODRR

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Hypertyrosinemia is observed in three inherited disorders of tyrosine metabolism. Hereditary Tyrosinemia Type I (HTT-I), or hepatorenal tyrosinemia, is an autosomal recessive disorder caused by mutation in the fumarylacetoacetate hydrolase (FAH) gene. HTT-I is associated with severe involvement of the liver, kidneys, and central nervous system, and is due to toxic accumulation of metabolites of tyrosine, such as succinylacetone. HTT-I is the inborn error with the highest incidence of progression to hepatocellular carcinoma. Elevated succinylacetone, in dried filter paper blood samples, or in plasma or urine, is pathognomonic and diagnostic for HTT-I and is the most reliable neonatal screening method. Liver transplantation is the definitive management, but the need for this is markedly decreased by the combined dietary and drug management. A diet low in tyrosine and phenylalanine, plus nitisinone (2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione) (NCTB) are considered the gold standard management options. Carnitine and 1,25-OH-vitamin D are adjuvant therapy. Strict follow up with succinylacetone level for monitoring of treatment should be done. Abdominal ultrasonography and abdominal computerized tomography scan or magnetic resonance imaging should also be done for surveillance of the possible development of hepatocellular carcinoma.

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Hematin therapy for the neurologic crisis of tyrosinemia

Cited by 31 publications

References 6 publications

Role of Delta-aminolevulinic Acid in the Symptoms of Acute Porphyria

Role of Delta-aminolevulinic Acid in the Symptoms of Acute Porphyria

Disorders of phenylalanine and tyrosine metabolism

Current management options for tyrosinemia

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