Genetics Northern California

Homocystinuria

Homocystinuria is an inherited disorder that occurs when the body lacks an enzyme needed to break down protein. When the enzyme is missing, homocysteine builds up in the body and causes damage to the nervous system (including the brain) and to the vascular system. The most common problems seen in people with homocystinuria include dislocation of the lenses of the eye, osteoporosis, and blood clots. If untreated, homocystinuria can lead to mental retardation and even death.

Everyone needs protein for growth and repair of body tissues, but the body cannot use the protein in food until it is broken down into smaller parts called amino acids. There are many different enzymes involved in the process of breaking down proteins. The most common enzyme involved with homocystinuria is called cystathionine beta sythetase (CBS), but there are several other enzymes that can also cause this condition.

Protein breaks down into many different amino acids. The amino acids involved in homocystinuria include methionine, homocysteine, and cysteine. As some proteins are broken down by bodies enzymes, they will create the amino acid, methionine. Methionine is then broken down into a second amino acid called homocysteine. The body then breaks down the homocysteine to make yet a third amino acid called cysteine. This is where most people with homocystinuria have trouble. They are unable to break down the homocysteine into cysteine because they do not have enough of the CBS enzyme. Not having enough CBS causes the levels of homocysteine to build up in the blood and the levels of cysteine to drop resulting in damage to the body.

Cause 
Homocystinuria is caused when the genetic instruction for any one of the related enzymes is not working. It is inherited in an autosomal recessive manner, meaning that each parent carries one non-working copy of the gene.  A person with the disorder has two non-working copies of the gene, one inherited from each parent. Since both copies are not working, the body is unable to make the enzyme.

Diagnosis
Infants, children and even adults that exhibit symptoms of homocystinuria can be identified with a simple blood test that measures the amount of homocysteine in the blood. Further testing measuring the amount and type of enzyme activity is done to confirm the diagnosis. Through early detection and prompt treatment, many serious effects of homocystinuria can be prevented.

Treatment/Services
The goal of treatment for homocystinuria is to keep the level of homocysteine in the blood as consistently low as possible. This will help prevent many of the problems caused by having high levels. The treatment itself consists of four main parts: diet, formula, supplements, monitoring.

  1. Diet: Please keep in mind that when we refer to "eating" that this includes any eating, drinking, swallowing, and chewing. When we refer to "foods," this includes all foods, drinks, medications, and even gum.

    Some people with homocystinuria must cut down on the amount of protein that they eat in order to lower their homocysteine levels. These individuals must learn what types of foods are highest in protein (and methionine) and limit these foods. Some examples of foods high in protein include all types of meat (e.g., chicken, pork, beef, seafood), all types of dairy (e.g., milk, yogurt, cheese, whipped cream, ice cream, etc.), all types of beans and nuts (e.g., pinto beans, peanuts, etc.), and eggs.

    People with homocystinuria who must avoid foods high in protein must also must also learn what foods have some amount of protein and ways to measure how much. Some individuals, depending on the severity of their disorder, are given a daily limit of the protein they can eat. It is okay for people with homocystinuria to eat some protein because, unlike an allergy, the protein will not cause them to have an "allergic" reaction. In fact, people with homocystinuria must eat some protein every day as everyone needs some protein in order to get enough homocysteine for growth and development. The trick is not to eat too much. This is done by learning to count and keep track of the amount they consume throughout the day.

    One of the main problems in following a low-protein diet is nutritional balance. Foods that are low in protein tend to be high in either fat or sugar or both. While some low-protein foods can be very nutritious, such as low-protein vegetables and fruit, others offer mostly "empty" calories. Foods that are high in "empty" calories supply a person with calories, but little nutrition. These calories are often needed for energy and growth but, when consumed in large amounts, can lead to obesity.

    Another problem is creating enough variety in the diet, especially for picky eaters. One way to increase variety is to eat low-protein specialty products. For instance, instead of avoiding all breads, pastas, and rice (which often have too much protein), people with homocystinuria can try some of the special low-protein versions of these foods. There are also many other types of low protein foods available, such as cheese, peanut butter, pizza, etc. As of July 2000, California State law (Senate Bill #148) requires all health insurance companies to provide low-protein specialty foods free of charge to all patients with a condition called PKU. Kaiser Permanente has expanded this requirement to include patients with any metabolic condition requiring a low-protein diet. The Regional Metabolic Clinic has contracted with several different specialty food companies to provide these products. In order not to be charged for these products, patients must fill out RMC order forms and return them to the clinic for review and approval. The coordinators will then forward these forms on to the company(ies) and the food will be delivered directly to the patient’s home. Limit: $2500 per patient per year.

  2. Formula: For those people who must avoid foods high in protein, the second part of the treatment for homocystinuria requires a special protein formula. Homocystinuria formulas are special because they contain all the amino acids a person needs, except methionine and extra cystine. It is almost impossible to get enough protein to stay healthy on a low-protein diet alone. Therefore, people with homocystinuria who need to follow such a diet must also drink formula in order to get enough protein without too much homocysteine. The formulas are also fortified with essential vitamins and minerals. Fortunately, today there are several different formulas for homocystinuria to choose from.

  3. Supplements/Medications: Some forms of homocystinuria can be treated with high doses of one of the B-vitamins called pyridoxine (vitamin B6). Vitamin B6 is a co-factor that helps the CBS enzyme work better. Other cofactors, Vitamin B12 and Folic Acid, may also help. Whether or not a person has the one of these forms of homocystinuria (either B6-responsive or B12/Folic Acid-responsive) is determined early in the treatment process. If the patient does not have this form of homocystinuria, no amount of Vitamin B6 will help. We strongly advise against self-treatment as it may cause unwanted side-effects or interfere with other treatments.

    Another supplement used to lower homocysteine levels is a medication called Betaine (also known as Cystadane). Betaine combines with homocysteine to change it back to methionine which can then be used for other functions in the body. There are some people with homocystinuria who do not need to follow a low-protein diet because they are able to keep their homocysteine levels low using vitamins and/or Betaine.

  4. Monitoring: The final part of the treatment for homocystinuria is monitoring, in order to know whether the other three parts of the treatment (diet, formula, and supplements) are actually working to keep the blood levels of homocysteine. It is best to find this out before the person with homocystinuria experiences any of the possible bad effects (as discussed above). Monitoring is done by testing the level of all the amino acids in the blood on a regular basis. The blood sample is taken at the hospital lab and sent down to the Metabolic Laboratory at Kaiser in Los Angeles for testing. It can take several days to a week to receive the results.

    If patients are taking Folic Acid or Vitamin B6 supplements, they must have a regular lab work to determine the levels of these vitamins in the blood in order to monitor their treatment. These blood tests can be done at most Kaiser labs.

    For all blood tests, a 3-day diet record is recommended. To complete a diet record all the food eaten over the period of three days must be written down along with the amount eaten. The blood test(s) should be taken on the 4th day, right after the diet record is completed. The diet record is an important part of interpreting the test results. For instance, if the homocysteine level is high, is it because the person is eating too much protein or too little? It is hard to get an accurate picture of what is happening inside the body without having the information provided by the diet record.

    Other tests - Patients are regularly weighed and measured at clinic and regular doctor visits in order to monitor their growth and development. School reports can also help identify any learning disabilities.

RESOURCES

Homocystinuria - General information about homocystinuria provided by the U.S. National Library of Medicine. Also includes links to related websites.

Homocystinuria - A handout on homocystinuria created by the University of Tennessee Health Science Center.

Reference Books
Low Protein Cookery for PKU (Please note: this book is helpful for all low-pro diets.)
by Virginia Schuett
Published by the University of Wisconsin Press, Madison, WN, 1997
Available through Kaiser's Regional Metabolic Clinic

The Complete IEP Guide published by Nolo Press
This book explains every nuance of the IEP process in lay terms. It provides clear concise explanations, definitions, and descriptions backed by legal codes (code reference numbers are included after every section). It also includes practical suggestions on how to deal with any problems that may arise.

How to Teach Nutrition to Kids
by Connie Liakos Evers, MS, RD
Published by 24 Carrot Press, Tigard, OR, 1995

Positive Discipline
By Jane Nelson, EdD
Published by Ballantine Books, New York, NY

Positive Discipline: The First Three Years
By Jane Nelson, EdD
Published by Ballantine Books, New York, NY

Positive Discipline for PreSchoolers
By Jane Nelsen, EdD, Cheryl Erwin, & Roslyn Duffy

Positive Discipline for Teenagers
By Jane Nelson, EdD, and Lynn Lott, MA
Published by Prima Publishing, Roseville, CA, 2000

Positive Time Out and 50 Other Ways to Avoid Power Struggles in Homes and Classrooms
By Jane Nelsen, EdD

Social Security Disability: Getting & Keeping Your Benefits published by Nolo Press
A legal guidebook to navigating the Social Security system written in plain-English. Helps the layperson to understand Supplemental Security Income (SSI) and Social Security Disability Insurance (SSDI) and the laws behind them (includes legal reference codes after each section).

Temperament Tools: Working with Your Child's Inborn Traits
By Helen Neville and Diane Clark Johnson
Published by Parenting Press, Inc., Seattle, WA, 1998

We're Different, We're the Same by Bobbi J. Kates. Illustrated by Joe Mathieu.
Published in 1992 by Random House. Suggested ages: 4-8
Sesame Street characters learn to appreciate their differences and discover that they still have many things in common.

Why Can't I Eat That!: Helping Kids Obey Medical Diets
By John F. Taylor, PhD, and R. Sharon Latta
Published by R & E Publishers, Saratoga, CA, 1987