Links to other pages within Patient UK which are related to this topic:
Experience | News | Products | Other
Print options:   Other options:   Bookmark and Share

This is a PatientPlus article. PatientPlus articles are written for doctors and so the language can be technical. However, some people find that they add depth to the articles found in the other sections of this website which are written for non-medical people.

Homocystinuria

Post your experience

This metabolic disorder is characterised by an increased blood and urine concentration of homocysteine - a sulphur-containing amino acid.
There are seven distinct types:

  1. Cystathionine β-synthase (CBS) deficiency
  2. 5,10-Methylenetetrahydrofolate reductase deficiency
  3. Deficiency of cobalam in coenzyme synthesis - consists of five subtypes (cblC, -D, -E, -F and -G)
Cystathionine β-synthase deficiency

Pathophysiology

Results from reduced activity of the enzyme cystathionine β-synthase which is involved in the conversion of methionine to cysteine. The enzyme is mapped to gene locus 21q22.1 Homocysteine and methionine accumulate in tissues and interfere with the cross-linking of collagen fibres.

Epidemiology

The G307 S mutation is the most common cause of homocystinuria in patients of Celtic origin. Guthrie testing has shown the incidence to be 1 in 344,000 worldwide but it is much higher in Ireland (1 in 65,000). All cases are inherited as autosomal recessive. 50% are responsive to pyridoxine (vitamin B6) and tend to have milder disease.1

Clinical findings

  • Raised plasma homocysteine that results in homocystinuria and raised plasma methionine levels.2
  • 80% of homozygous patients will develop ocular abnormalities and half of these will have mental retardation.
  • Abnormalities manifest themselves by age 3-4 years.

Heterozygous carriers (1 in 70 of general population) have hyperhomocystinaemia - raised plasma homocysteine levels with no homocystinuria. Their risk of premature cardiovascular disease is increased.

Presentation

  • Skeletal features: Marfanoid habitus with normal to tall stature (occasionally failure to thrive in infancy), fine, brittle hair, hypopigmentation, high arched palate, crowded teeth, arachnodactyly, limited joint mobility, pectus excavatum/carinatum, kyphoscoliosis
  • Eyes: dislocation of lens usually downward and medially (ectopia lentis), myopia, glaucoma
  • CNS: mental retardation (average IQ = 80; 30% have normal IQ), seizures, cerebrovascular events, psychiatric disorders3

Investigations

  • The cyanide-nitroprusside test is an easy way to detect increased excretion of sulfhydryl-containing compounds in the urine.
  • Urine amino acids - elevated homocysteine and methionine levels.
  • Plasma levels of free methionine and homocysteine (methionine is raised in CBS deficiency and low or normal in those with other causes of homocystinuria).
  • Ophthalmology tests to detect myopia and dislocated lens.
  • Diagnosis depends on measurement of CBS activity in tissues, e.g. liver biopsy, skin biopsy.
  • Imaging e.g. X-rays or DEXA scan to detect osteoporosis.

Complications

Management

  • Effective treatment requires early diagnosis and initiation of therapy.
  • Try pyridoxine in all - increases CBS activity.
  • Methionine-restricted, cystine-supplemented diet for those who do not respond to pyridoxine (betaine may also be useful).
  • Methionine restriction has been shown to prevent mental retardation and reduce the rate of lens dislocation and seizure activity.
  • Pyridoxine supplementation for responders (usually 50% of affected patients).
  • Pyridoxine treatment of those who are detected late reduces the rate of thromboembolic events.
  • Avoid folate deficiency.
  • Consider primary prevention of cardiovascular disease, e.g. aspirin, statin.
  • Referral to specialists as indicated by clinical picture e.g. ophthalmologist, psychiatrist.

Prognosis

25% of patients will die by the age of 30 years from vascular related diseases. Increased homocysteine levels is an independent risk factor for coronary, cerebrovascular and peripheral vascular disease and deep vein thrombosis.4

Differential diagnosis

Marfan's syndrome is the main differential diagnosis to consider.

Marfan's syndrome5
Homocystinuria
  • Autosomal dominant
  • Aortic incompetence
  • Upwards lens dislocation
  • Normal mentality
  • Scoliosis
  • Flat feet
  • Herniae
  • Autosomal recessive
  • Heart rarely affected
  • Downwards lens dislocation
  • Mental retardation
  • Recurrent thromboses
  • Osteoporosis

The following conditions also elevate urinary cysteine levels:

Other causes of homocystinuria

All other forms of homocystinuria result from enzyme abnormalities involved in the conversion of homocysteine to methionine. This is catalysed by homocysteine:methyltetrahydrofolate methyltransferase (also called methionine synthase) and its two cofactors - methyltetrahydrofolate and methylcobalamin (methyl-vitamin B12).

These cases are severe and rarely reported; thus experience with treatments and other data are limited.


Document references
  1. Homocystinuria, Online Mendalian Inheritance in Man (OMIM).
  2. Finkelstein JD; Inborn errors of sulfur-containing amino acid metabolism. J Nutr. 2006 Jun;136(6 Suppl):1750S-1754S. [abstract]
  3. Gomber S, Dewan P, Dua T; Homocystinuria: a rare cause of megaloblastic anemia. Indian Pediatr. 2004 Sep;41(9):941-3. [abstract]
  4. Brattstrom L, Wilcken DE; Homocysteine and cardiovascular disease: cause or effect? Am J Clin Nutr. 2000 Aug;72(2):315-23. [abstract]
  5. Summers KM, West JA, Peterson MM, et al; Challenges in the diagnosis of Marfan syndrome. Med J Aust. 2006 Jun 19;184(12):627-31. [abstract]
Acknowledgements EMIS is grateful to Dr Hayley Willacy for writing this article and to Dr Gurvinder Rull for earlier versions. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2009.
Document ID: 2268
Document Version: 21
Document Reference: bgp2432
Last Updated: 16 Oct 2009
Planned Review: 16 Oct 2011

The authors and editors of this article are employed to create accurate and up to date content reflecting reliable research evidence, guidance and best clinical practice. They are free from any commercial conflicts of interest. Find out more about updating.

Links to other pages within Patient UK which are related to this topic:
Experience | News | Products | Other
Print options:   Other options:   Bookmark and Share
Want to search some more? Use the Google Search box below to search our site.

Related pages in Patient UK

Your Experience (^ top of page)

 Please add your experience about this condition / medicine

Latest Health News

 View current health news

Medical equipment


Visit the Patient UK Medical Equipment shop

Books


Visit the Patient UK shop

Other - Useful resources (^ top of page)

Pictures, diagrams, photos, images, etc.
Evidence based medicine
Online textbooks and journals
UK Guidelines
Online Videos
Medline
Other good health sites

Want to search some more? Use the Google Search box below to search our site.

Advertisements















Disclaimer: Patient UK has no control over the content of any external links above. Inclusion does not imply endorsement by Patient UK.

Want to advertise on this site? Find out how >>

Clicking here will take you to the foot of this page where you'll find a list of Information Leaflets which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of Support Groups which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of Medicines & Drugs which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of diagrams which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of PatientPlus (detailed reference) articles which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of UK Guidelines which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of other selected websites which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of Poems and Stories which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of Operations and Procedures which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of Online Videos which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find links through to our interactive forum.
Here you can follow a link to view existing patient experiences on this subject, or to add your own
Clicking here will take you to the foot of this page where you'll find links to news stories on this subject in our Online Newspaper
Clicking here will take you to the foot of this page where you'll find links to related products
Clicking here will take you to the foot of this page where you'll find links to other useful sources of information
Click here to open a printer-friendly version of this document, in a new window, together with the print dialogue box
Click here to open this document in PDF format
This will offer you the usual PDF options i.e. document navigation, search, zoom and formatted print
Note: this is the best way to print the document
Click here to listen to the MP3 audio recording of this document
Click here to download the audio recording of this document as a podcast, for listening to at your leisure
Click here to open our Dictionaries and Glossaries page
Click here to see related products in our Online Pharmacy
Note: this will open in a new window
Click here to add this page to a social bookmarking site of your choice
Click here if you want to find out more about social bookmarking. This link will take you to the Wikipedia explanation
Note: this will open in a new window
Clicking here will take you to the foot of this page where you'll find a list of Information Leaflets which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of Support Groups which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of Medicines & Drugs which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of diagrams which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of PatientPlus (detailed reference) articles which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of UK Guidelines which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of other selected websites which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of Poems and Stories which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of Operations and Procedures which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find a list of Online Videos which are related to the topic you are currently viewing
Clicking here will take you to the foot of this page where you'll find links through to our interactive forum.
Here you can follow a link to view existing patient experiences on this subject, or to add your own
Clicking here will take you to the foot of this page where you'll find links to news stories on this subject in our Online Newspaper
Clicking here will take you to the foot of this page where you'll find links to related products
Clicking here will take you to the foot of this page where you'll find links to other useful sources of information
Click here to open a printer-friendly version of this document, in a new window, together with the print dialogue box
Click here to open this document in PDF format
This will offer you the usual PDF options i.e. document navigation, search, zoom and formatted print
Note: this is the best way to print the document
Click here to listen to the MP3 audio recording of this document
Click here to download the audio recording of this document as a podcast, for listening to at your leisure
Click here to open our Dictionaries and Glossaries page
Click here to see related products in our Online Pharmacy
Note: this will open in a new window
Click here to add this page to a social bookmarking site of your choice
Click here if you want to find out more about social bookmarking. This link will take you to the Wikipedia explanation
Note: this will open in a new window
Click here to return to the home page
Click here to read our 'About Us' page
Go to the Emis Access website, where you can book an appointment with your GP, order a repeat prescription or view you medical record online.
Note: this will open in a new window
View and/or join in discussion about health, lifestyle and disease in our interactive forum.
Note: this will open in a new window
Visit our pharmacy product price comparison website
Go to our online newspaper for current medical news and commentary.
Note: this will open in a new window
Adverts on this site do not influence the medical content. Click to read more.
Adverts on this site do not influence the medical content. Click to read more.
This organsition has been certified as a producer of reliable health and social care information.

Click the image to find out more.