Liverin Liquid

Indications

• Homocystinuria
• Type I Gaucher's disease (specialist use only)

Dosage

Children: Refer to BNF for Children for specific dosing guidelines.

Adults: Refer to BNF for specific dosing guidelines.

Mechanism of action

Betaine acts as a methyl donor in the transsulfuration pathway, facilitating the conversion of homocysteine to methionine and thereby reducing homocysteine levels.

Pharmacodynamics

Betaine reduces plasma homocysteine concentrations, which is beneficial in conditions such as homocystinuria. It also has a role in osmoregulation and may influence cellular metabolism.

Pharmacokinetics

Betaine is well absorbed after oral administration, with a bioavailability of approximately 90%. It is primarily excreted in the urine as betaine and its metabolites.

Adverse effects

• abdominal discomfort
• agitation
• alopecia
• appetite decreased
• brain oedema
• diarrhoea
• glossitis
• irritability
• nausea
• skin reactions
• urinary incontinence
• vomiting
• arthralgia
• asthenia
• chest discomfort
• dizziness
• dyspnoea
• fever
• flushing
• gastrointestinal discomfort
• headache
• hypersensitivity
• hypertension
• hypotension
• infusion-related reactions
• nausea
• pain
• skin reactions
• tachycardia

Interactions

• may be given with supplements of Vitamin B12, pyridoxine, and folate under specialist advice

Precautions

• use in conjunction with dietary restrictions
• monitor plasma-methionine concentration before and during treatment
• interrupt treatment if symptoms of cerebral oedema occur
• use with caution in pregnancy due to limited information
• use with caution in breastfeeding due to lack of information

Pregnancy

Manufacturer advises avoid unless essential-limited information available.

Breast-feeding

Manufacturer advises caution-no information available.

Storage

Store in a cool, dry place; protect from light.

Formulations

• Cystadane oral powder 1 gram per 1 gram

Mechanism of action

Homocystinuria is a hereditary disorder characterized by high levels of the amino acid homocysteine. This condition can be caused by deficiencies or defects in cystathionine beta-synthase (CBS), 5,10-methylenetetrahydrofolate reductase (MTHFR), and cobalamin cofactor metabolism (cbl). CBS converts homocysteine to cystathionine, and a deficiency in this enzyme can lead to an accumulation of homocysteine. MTHFR is responsible for producing 5-methyltetrahydrofolate, a methyl donor that participates in the conversion of homocysteine back to methionine; therefore, an MTHFR deficiency can also lead to homocystinuria. Additionally, a defect in cobalamin (vitamin B12) cofactor metabolism can lead to homocystinuria, since a metabolite of cobalamin (methylcobalamin) promotes the conversion of homocysteine to methionine. Betaine transfers a methyl group via the enzyme betaine homocysteine methyl transferase (BHMT), converting homocysteine back into methionine and dimethylglycine (DMG). In patients with homocystinuria, betaine reduces homocysteine levels and improves health outcomes. Betaine acts as metabolic intermediate in transmethylating processes (creatine and methionine synthesis). Betaine acts as a methyl group donor in the remethylation of homocysteine to methionine in patients with homocystinuria. This reduces toxic concentrations of homocysteine, usually to 20 to 30% or less of pretreatment concentrations. Betaine or trimethylglycine is a quarternary ammonium compound that was first discovered in the juice of sugar beets (Beta vulgaris). Betaine is a metabolite of choline ... and is a substrate in one of the two recycling pathways that convert homocysteine to L-methionine. The other and principal recycling reaction is catalyzed by the enzyme methionine synthase and uses methylcobalamin as a cofactor and 5-methyltetrahydrofolate as a cosubstrate. Betaine-homocysteine methyltransferase (BHMT) is a zinc metalloenzyme which catalyzes the transfer of a methyl group from betaine to homocysteine in the formation of methionine. BHMT is found in the liver and kidneys and may also exist in brain tissue. Betaine acts to lower homocysteine levels in some with primary hyperhomocysteinemia/homocystinuria via this enzyme.

Pharmacodynamics

Betaine decreases plasma homocysteine concentrations in homocystinuria cases caused by deficiencies or defects in cystathionine beta-synthase (CBS), 5,10-methylenetetrahydrofolate reductase (MTHFR), and cobalamin cofactor metabolism (cbl). The decrease of homocysteine is estimated to be 20-30% of pre-treatment levels. Betaine supplementation in patients with homocystinuria also improves metabolic abnormalities in cerebrospinal fluid. Reports have shown that depending on the type of homocystinuria, the therapeutic effectiveness of betaine alone may be limited, insufficient to decrease total homocysteine levels and prevent clinical symptoms. In patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency, betaine should be used when serum total homocysteine levels remain high despite dietary therapy. Patients taking betaine for several years do not show evidence of tolerance. Also, betaine concentrations are not correlated with homocysteine concentrations. In patients with MTHFR deficiency and cbl defects, betaine may increase methionine and S-adenosyl methionine (SAM) plasma levels. Patients with CBS deficiency without a dietary restriction of methionine may accumulate excessive amounts of methionine. Clinical data shows that in patients with CBS deficiency, increased plasma methionine levels were associated with cerebral edema.