HMG-CoA lyase deficiency (also known as 3-hydroxy-3-methylglutaryl-CoA lyase deficiency) is a rare genetic condition that prevents the body from breaking down the amino acid leucine, which makes up many proteins, and stops the body from making ketones, which are compounds that are used for energy during periods without food (fasting).
HMG-CoA lyase deficiency usually affect babies before one year of age and causes episodes of vomiting, diarrhea, dehydration, extreme tiredness, low muscle tone, low blood sugar levels, and a buildup of harmful compounds can cause the blood to become too acidic (metabolic acidosis). If not treated, additional symptoms include breathing problems, seizures, coma, and death.
HMG-CoA lyase deficiency is also known as:
3-hydroxy-3-methylglutaryl-CoA lyase deficiency
HMG-CoA Lyase Deficiency
HMGCL Deficiency
HL Deficiency
Hydroxymethylglutaric aciduria
Defect in leucine metabolism
3-hydroxy-3-methylglutaric aciduria
HMG
HMG-CoA lyase deficiency is a rare condition and its exact frequency is unknown. To date, it has been reported in fewer than 100 individuals worldwide. Most people diagnosed with this disorder have been from Spain, Portugal, or Saudi Arabia.
Frequently Asked Questions About HMG-CoA lyase deficiency
Who else in my family should I test for HMG-CoA lyase deficiency?
Siblings of an individual with HMG-CoA lyase deficiency can be tested using blood, urine or skin samples to determine if they are also affected. Additionally, if both genetic changes in the affected individual have been identified, other family members, such as the parents’ siblings and cousins can have genetic testing to see if they are carriers and at risk of passing the condition on to future children.
Where do I find people with HMG-CoA lyase deficiency?
While there is currently no support group specifically for HMG-CoA lyase deficiency, there are other groups that help provide support for families with many metabolic conditions, including HMG-CoA lyase deficiency. See below for
FOD (Fatty Oxidation Disorder) Family Support Group
Telephone: 517-381-1940
E-mail: [email protected]
Website: http://www.fodsupport.org
Organic Acidemia Association
Telephone: 763-559-1797
E-mail: [email protected]
Website: http://www.oaanews.org/
Where can I get genetic testing for HMG-CoA lyase deficiency?
Diagnostic laboratories that perform genetic testing for HMG-CoA lyase deficiency can be found by clicking here.
When can I stop treatment for HMG-CoA lyase deficiency?
What specialist doctors should I see with HMG-CoA lyase deficiency?
HMG-CoA deficiency is a genetic metabolic condition, and therefore referral to a genetic and/or metabolic clinic is appropriate. Additionally, it is important to work with a dietician to develop an appropriate feeding plan.
What is HMG-CoA lyase deficiency?
HMG-CoA lyase deficiency (also known as 3-hydroxy-3-methylglutaryl-CoA lyase deficiency) is a rare genetic condition that prevents the body from breaking down the amino acid leucine, which makes up many proteins, and stops the body from making ketones, which are compounds that are used for energy during periods without food (fasting).
HMG-CoA lyase deficiency usually affect babies before one year of age and causes episodes of vomiting, diarrhea, dehydration, extreme tiredness, low muscle tone, low blood sugar levels, and a buildup of harmful compounds can cause the blood to become too acidic (metabolic acidosis). If not treated, additional symptoms include breathing problems, seizures, coma, and death.
What gene causes HMG-CoA lyase deficiency?
HMG-CoA lyase deficiency is caused by changes (mutations) in the gene HMGCL. This gene provides instructions for making an enzyme called 3-hydroxymethyl-3-methylglutaryl-CoA lyase (HMG-CoA lyase). This enzyme is found in mitochondria, which are the energy-producing centers of the cell and works to break down proteins and fats from food.
What are the signs and symptoms of HMG-CoA lyase deficiency?
Signs of HMG-CoA lyase deficiency usually become apparent in the first year of life. Symptoms include periods or episodes of vomiting, diarrhea, dehydration, extreme tiredness, and low muscle tone. During these episodes, blood sugar levels can drop very low (hypoglycemia), and a buildup of harmful compounds can cause the blood to become too acidic (metabolic acidosis). If this condition is not treated, it can lead to breathing problems, seizures, coma, enlargement of the liver (hepatomegaly), and death. Episodes are often triggered by an infection, going too long without food, strenuous exercise, or other types of stress.
What are the first steps after an initial diagnosis of HMG-CoA lyase deficiency?
After a diagnosis of HMG-CoA lyase deficiency, it is important to work with a metabolic doctor and a dietician in addition to your primary care doctor. Timely treatment is important to prevent metabolic crises and the additional symptoms that follow. The first step in treatment is to avoid long periods without eating (fasting), which will help prevent a metabolic crisis. Additionally, adoption of a low-leucine diet, which often includes medical foods and formula, is important to prevent a dangerous build-up of the amino acid leucine.
Is there newborn screening for HMG-CoA lyase deficiency?
Testing for HMG-CoA lyase deficiency is performed as part of newborn screening in all states in the US. This testing, known as biochemical testing, looks for abnormalities in the levels of compounds in blood. Newborn screening helps to identify individuals with conditions that are treatable as early as possible so treatment and intervention can begin as quickly as possible.
Is there more than one test for HMG-CoA lyase deficiency?
In addition to the newborn screening blood test and genetic test, HMG-CoA lyase deficiency can be tested for through a urine test.
Is there clinical research happening on HMG-CoA lyase deficiency?
As of January 19th 2019, there are no clinical research trials involving HMG-CoA lyase deficiency. If you are interested in searching for clinical research specifically for HMG-CoA lyase deficiency, visit [link url="www.clinicaltrials.gov” target=”_blank”>www.clinicaltrials.gov and search for "HMG-CoA lyase deficiency".
Is there a treatment for HMG-CoA lyase deficiency?
Treatment of HMG-CoA lyase deficiency is often needed throughout life. Not all treatments are right for all patients. Make sure to consult with your physician before beginning, stopping, or changing any treatments.
Treatment usually consists of:
1. Avoiding going a long time without food (fasting)
Infants and young children with HMG-CoA lyase deficiency need to eat frequently to prevent a metabolic crisis. A metabolic specialist will determine how often a child needs to be fed. In general, it is often suggested that infants be fed every four to six hours. However, some babies need to eat even more frequently. It is important that infants be fed during the night, and they may need to be woken up to eat if they do not wake up on their own. A metabolic specialist and dietician will help develop an appropriate feeding plan. Your doctor should also provide a ‘sick day’ plan, tailored to each patient’s specific needs, follow during illnesses or other times when a patient will not or cannot eat. Over time, the frequency of feedings will likely change. Your medical care team will continue to adjust the feeding schedule over time.
2. Sticking to a low-leucine diet
A diet low in leucine and limited amounts of fat and protein is often recommended. Most food in the diet will be carbohydrates (bread, cereal, pasta, fruit, vegetables, etc.). Carbohydrates give the body many types of sugar that can be used as energy. Eating a diet high in carbohydrates and low in protein and fat can help prevent low blood sugar (hypoglycemia) and metabolic crises.
Foods high in protein and fat that patients may need to avoid or limit:
Is HMG-CoA lyase deficiency contagious?
HMG-CoA lyase deficiency is a genetic disorder which is caused by genetic changes (variants) that are inherited, but is not contagious. People cannot catch HMG-CoA lyase deficiency through touch, coughing, handshakes, etc.
I had genetic testing for my ancestry. Can it give me information about HMG-CoA lyase deficiency?
Genetic tests for ancestry and other online direct-to-consumer (DTC) tests, such as 23andMe do not provide information about HMG-CoA lyase deficiency. The technology used in these tests is different from the technology used in a clinical laboratory test for HMG-CoA lyase deficiency. Although these types of tests look at your DNA, they are only looking at a small portion of the genes in your body, which are specific to ancestry or other traits. Testing for HMG-CoA lyase deficiency looks at the whole HMGCL gene.
If you would like to discuss the results of your ancestry or other direct-to-consumer test, talk with your doctor. You can also discuss the reports with a medical geneticist or genetic counselor.
You can find a genetic counselor near you by clicking here.
How is HMG-CoA lyase deficiency inherited?
HMG-CoA lyase deficiency is inherited in an autosomal recessive pattern. This means both copies of the gene have changes, or variants, that cause the gene to not work correctly. The parents of an individual with an autosomal recessive condition each carry one copy of the non-working gene, but they themselves typically do not show signs and symptoms of the condition.
How do I get tested for HMG-CoA lyase deficiency?
Genetic testing is available for HMG-CoA lyase deficiency. Genetic testing looks for changes in the DNA that cause the genes to function incorrectly. Genetic testing is typically ordered by a geneticist or genetic counselor. You can find a genetic counselor near you at nsgc.org. Laboratories that test for HMG-CoA lyase deficiency at the Genetic Testing Registry.
How do I get early intervention for my child with HMG-CoA lyase deficiency?
Early intervention services are available to babies and toddlers who have a developmental delay or disability caused by HMG-CoA lyase deficiency. Each state has their own eligibility criteria. Typically, this begins with an evaluation to learn more about the child’s delay or disability, and to learn more about what areas they could use more help in.
Some resources are available here.
Additionally, your child’s doctor, genetic counselor, or other healthcare provider can give you more information about early intervention services in your area.
How do I find clinical research on HMG-CoA lyase deficiency?
To search for clinical research and trials for HMG-CoA lyase deficiency, visit [link url="www.clinicaltrials.gov” target=”_blank”>www.clinicaltrials.gov and search for "HMG-CoA lyase deficiency".
How do I find a center of excellence in HMG-CoA lyase deficiency?
To find a center that specializes in the treatment of HMG-CoA lyase deficiency, click here (in the US and Canada) or click here (in Europe).
How common is HMG-CoA lyase deficiency?
HMG-CoA lyase deficiency is a rare condition and its exact frequency is unknown. To date, it has been reported in fewer than 100 individuals worldwide. Most people diagnosed with this disorder have been from Spain, Portugal, or Saudi Arabia.
Do people with HMG-CoA lyase deficiency have normal life spans?
If HMG-CoA lyase deficiency is diagnosed early and treated appropriately, life expectancy is not shorter than normal. However, the condition is fatal in up to 20% (1 in 5) of cases. Neurological damage obtained during metabolic crises or hypoglycemic coma may be irreversible, potentially leading to hearing or vision loss, learning difficulties, and intellectual or cognitive impairments.
Can you tell someone has HMG-CoA lyase deficiency by looking at them?
There are no obvious physical symptoms of HMG-CoA lyase deficiency. Affected individuals do not have distinctive facial features or other physical abnormalities.
Can I prevent having a child with HMG-CoA lyase deficiency?
Couples who are both carriers of HMG-CoA lyase deficiency and are at-risk of having a child with the condition can discuss their reproduction options with a doctor or genetic counselor.
Options include:
Can I get tested for HMG-CoA lyase deficiency if I didn’t have newborn screening?
Testing is available for individuals with a clinical suspicion of HMG-CoA lyase deficiency if they have not had a newborn screening test. If you or your child are experiencing symptoms of HMG-CoA lyase deficiency, you should speak to your doctor or genetic counselor to see if genetic or biochemical testing is right for you.
You can find a genetic counselor near you by clicking here.
Can I get pregnant if I have HMG-CoA lyase deficiency?
There are limited reported cases of pregnancy in women with HMG-CoA lyase deficiency. As of January 2019, there are only three reported women who have become pregnant with HMG-CoA lyase deficiency, two of which made it to term and delivery. Complications in these cases include metabolic decompensation (often characterized by abnormal behavior, drowsiness, and a glazed look) in the first trimester or during labor and delivery, metabolic acidosis, premature rupture of membranes, intrapartum bleeding requiring transfusion, tachycardia, hypertension, and miscarriage. Additionally, first trimester nausea and vomiting appears to be worse that in typical pregnancies. It is recoommended that pregnant patients with HMG-CoA lyase deficiency be followed and treated at a tertiary care center during pregnancy, delivery, and the following birth by a biochemical geneticist, dietitian, and high-risk obstetrician.
Are there other names for HMG-CoA lyase deficiency?
HMG-CoA lyase deficiency is also known as:
Are there good support groups for HMG-CoA lyase deficiency?
Support for individuals and families with HMG-CoA lyase deficiency can be found through the following organizations.
FOD (Fatty Oxidation Disorder) Family Support Group
Telephone: 517-381-1940
E-mail: [email protected]
Website: http://www.fodsupport.org
Genetic Metabolic Dietitians International
E-mail: [email protected]
Website: http://www.gmdi.org/
Organic Acidemia Association
Telephone: 763-559-1797
E-mail: [email protected]
Website: http://www.oaanews.org/
