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Homocystinuria

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Introduction

The Questions and Answers that follow aim to provide an introduction to homocystinuria for parents and other family members. Following those, we offer links to selected resources for more information and support and a list of valuable services.
Note that we use the term doctor to refer to physicians, nurse practitioners, physician assistants, and other licensed clinicians who may care for your child.
More information about many topics relevant to children with homocystinuria and many other chronic conditions and their families can be found in the left menu. Detailed information aimed at primary care doctors can be found in our Homocystinuria module. Information can also be found in the Homocystinuria Newborn Screening Page.

What is homocystinuria and what causes it?

Homocystinuria is an autosomal recessive inherited metabolic disorder caused by a defect in an enzyme that converts the amino acid homocysteine to cystathionine, resulting in accumulation of homocysteine in the blood and its excretion in urine. There are two main variants or types of homocystinuria: one is responsive to vitamin B6 (pyridoxine, the cofactor of cystathionine beta synthase) and the other does not respond to vitamin B6 and usually has more-pronounced symptoms than the first variant. It may affect the cardiovascular, musculoskeletal, and the central nervous systems. [American: 2012]

What are the symptoms of homocystinuria?

With early treatment, there may be fewer symptoms and complications. Without treatment, symptoms vary widely.
Initial symptoms in infants and toddlers may include:
  • developmental delay
  • emotional and behavior problems
  • ectopia lentis (dislocation of the ocular lens) or severe myopia (nearsightedness)
Findings in older children and adults may include:
  • Marfanoid habitus: tall/thin build; long fingers, arms, and legs
  • genu valgum (knocked knees), pes cavus (high arch/instep)
  • osteoporosis (weak/brittle bones)
  • malar flush (red cheeks)
  • decreased hair, skin, iris pigmentation
  • seizures
  • vascular disease and stroke
  • psychiatric abnormalities
  • intellectual disabilities

How is it diagnosed?

Newborn metabolic screening measures an elevation of methionine that increases with homocysteine in affected individuals. Infants with milder variants, or in whom newborn screening is obtained too early, can be missed by newborn screening. There are many other types of homocystinuria caused by defects in the remethylation of homocysteine to methionine. These cases are not identified by most newborn screening programs because methionine is low and most programs do not have a low cut-off for methionine. The metabolic geneticist will test affected individuals to determine which variant is present. See the Portal's Newborn Disorder page on Homocystinuria for more information and response to a positive newborn screen.

What is the prognosis?

Infants identified by newborn screening and treated to correct the biochemical abnormalities appear to have fewer manifestations of the condition, including decreased incidence of intellectual disability and thromboembolic events. [Yap: 2000]

What is the risk for other family members or future babies?

Children from the same father and mother as the affected infant have a 1 in 4 chance of having homocystinuria. [New: 2010] Siblings of children with this condition should be screened with plasma amino acids and total plasma homocysteine. If the disease-producing mutation in the family has been identified, carrier testing can be performed.

What treatments/therapies/medications are recommended or available?

Blood levels of homocysteine are maintained as close as possible to the normal range by restricting methionine in the diet (usually through restricted protein intake) and adding methylfolate and methyl B12 supplementation, betaine treatment, and vitamin B6 (pyridoxine) supplementation. This treatment needs to be continued and monitored throughout life. Other individuals may benefit by antiplatelet treatment such as daily baby aspirin. Eye complications are treated surgically. Other complications are treated symptomatically (psychiatric problems, osteoporosis, etc.). Children with significant disabilities should receive developmental therapies.

How will my child and our family be impacted?

The family will be important in helping the child maintain a low-protein diet, restricting bread, pasta, eggs, dairy products, rice, nuts, and meat. Special formulas/powders are available with essential amino acids and no methionine or cystine. Keeping a diet record and completing blood tests will help manage the condition.

Can I breastfeed my baby who has just been diagnosed with homocystinuria?

Breastfeeding an infant with homocystinuria usually needs to be limited and should be discussed in detail with the metabolic genetics team. Formulas are usually used to supplement breastfeeding in order to limit methionine.

Resources

Information & Support

Where can I go for further information?

For Parents and Patients

Homocystinuria - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.

Homocystinuria (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.

Parent Information Sheet Homocystinuria - Confirmed Diagnosis (NHS) (PDF Document 336 KB)
Information for parents for when the results of the newborn blood spot screening are positive; National Institute for Health Research (UK).

Homocystinuria: A Guide for Parents of Babies Recently Screened for Homocystinuria (NECMP)
Information about homocystinuria for patients, including inheritance, diagnosis, maintaining a healthy diet, treatment, and testing of other children; from the New England Consortium of Metabolic Programs.

Boston Children’s Hospital Transition Toolkit for Homocystinuria (PDF Document 389 KB)
Includes health readiness assessments, metabolic conditions basics, and a transition plan for youth with homocystinuria. Sponsored by the New England Consortium of Metabolic Programs.

Tools

Boston Children's Hopsital Transition Toolkit (NECMP)
Includes health readiness assessments, metabolic conditions basics, and a transition plan for youth with metabolic conditions; New England Consortium of Metabolic Programs.

Care Notebook (UT Dept. of Health) (PDF Document 467 KB)
For families to track your child's care, health, and other information; with pages from 10 different states. Word document may be edited.

Services for Patients & Families in Rhode Island (RI)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Authors & Reviewers

Initial publication: July 2014; last update/revision: December 2015
Current Authors and Reviewers:
Author: Medical Home Team
Reviewer: Meghan Candee, MD

Page Bibliography

American College of Medical Genetics.
Homocystinuria: transition to adult health care ACT sheet.
2012; 2. https://www.acmg.net/StaticContent/ACT/Homocystinuria_Transition.pdf
Educational resource for clinicians providing care for patients with homocystinuria.

New England Consortium of Metabolic Programs.
Homocystinuria: a guide for parents of babies recently screened for homocystinuria.
(2010) https://www.newenglandconsortium.org/homocystinuria-hcu. Accessed on 12/2020.

Yap S, Naughten ER, Wilcken B, Wilcken DE, Boers GH.
Vascular complications of severe hyperhomocysteinemia in patients with homocystinuria due to cystathionine beta-synthase deficiency: effects of homocysteine-lowering therapy.
Semin Thromb Hemost. 2000;26(3):335-40. PubMed abstract