Homocystinuria

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Homocysteinuria
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Homocystinuria
Other namesCystathionine beta synthase deficiency or CBS deficiency[1]
Homocysteine
SpecialtyEndocrinology, medical genetics Edit this on Wikidata

Homocystinuria or HCU

autosomal recessive trait, which means a child needs to inherit a copy of the defective gene from both parents to be affected. Symptoms of homocystinuria can also be caused by a deficiency of vitamins B6, B12, or folate.[3]

Signs and symptoms

This defect leads to a multi-systemic disorder of the

cardiovascular system. Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of the amino acid homocysteine in the serum and an increased excretion of homocysteine in the urine. Infants appear to be normal and early symptoms, if any are present, are vague.[citation needed
]

Signs and symptoms of homocystinuria that may be seen include the following:

Cause

It is usually caused by the deficiency of the enzyme

folic acid, vitamin B12 and/or pyridoxine (vitamin B6).[3]

Diagnosis

The term homocystinuria describes an increased excretion of the

cobalamin (vitamin B12). In light of this, a combined approach to laboratory diagnosis is required to reach a differential diagnosis.[citation needed
]

CBS deficiency may be diagnosed by routine metabolic biochemistry.

mutations). In the first instance, plasma or urine amino acid analysis will frequently show an elevation of methionine and the presence of homocysteine. Many neonatal screening programs include methionine as a metabolite. The disorder may be distinguished from the re-methylation defects (e.g., MTHFR, methionine synthase deficiency, or the cobalamin defects) in lieu of the elevated methionine concentration.[7] Additionally, organic acid analysis or quantitative determination of methylmalonic acid should help to exclude cobalamin (vitamin B12) defects and vitamin B12 deficiency giving a differential diagnosis.[8]

The laboratory analysis of homocysteine itself is complicated because most homocysteine (possibly above 85%) is bound to other thiol amino acids and proteins in the form of

derivatisation with a fluorescent agent, thus giving a true reflection of the quantity of homocysteine in a plasma sample.[9]

Treatment

No specific cure has been discovered for homocystinuria; however, many people are treated using high doses of vitamin B6 (also known as

MTHFR enzyme pathway and multiple glutathione-related pathways, may also be used.[citation needed
]

Betaine (N,N,N-trimethylglycine) is used to reduce concentrations of homocysteine by promoting the conversion of homocysteine back to methionine, i.e., increasing flux through the re-methylation pathway independent of folate derivatives (which is mainly active in the liver and in the kidneys). The re-formed methionine is then gradually removed by incorporation into body protein. The methionine that is not converted into protein is converted to S-adenosyl-methionine which goes on to form homocysteine again. Betaine is, therefore, only effective if the quantity of methionine to be removed is small. Hence treatment includes both betaine and a diet low in methionine. In classical homocystinuria (CBS, or cystathione beta synthase deficiency), the plasma methionine level usually increases above the normal range of 30 micromoles/L and the concentrations should be monitored as potentially toxic levels (more than 400 micromoles/L) may be reached.[citation needed]

Recommended diet

Low-protein food is recommended for this disorder, which requires food products low in particular types of amino acids (e.g., methionine).[citation needed][11]

Prognosis

The life expectancy of patients with homocystinuria is reduced only if untreated. It is known that before the age of 30, almost one quarter of patients die as a result of thrombotic complications (e.g., heart attack).[citation needed]

Society and culture

One theory suggests that Akhenaten, a pharaoh of the eighteenth dynasty of Egypt, may have had homocystinuria.[12]

See also

References

  1. ^ a b Online Mendelian Inheritance in Man (OMIM): 236200
  2. ^ "Homocystinuria". 9 May 2018.
  3. ^
    OCLC 948547794.{{cite book}}: CS1 maint: location missing publisher (link
    )
  4. PMID 18423051
    .
  5. ISBN 978-0-306-48238-0
    . Retrieved 12 April 2010.
  6. ISBN 978-1437727883
    .
  7. ISBN 978-3540425427. {{cite book}}: |last= has generic name (help
    )
  8. PMID 14709635
    .
  9. PMID 10420601
    .
  10. S2CID 21228831
    .
  11. S2CID 260318647
    .
  12. PMID 20402329
    .

Further reading

External links

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