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Disease Profile
HIBCH deficiency
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
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Age of onset
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ICD-10
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Inheritance
Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.
Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.
X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.
Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.
Not applicable
Other names (AKA)
Neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency; 3-Hydroxyisobutyryl-CoA hydrolase deficiency; Beta-hydroxyisobutyryl-CoA deacylase deficiency;
Categories
Congenital and Genetic Diseases; Nervous System Diseases
Summary
HIBCH deficiency is a rare
HIBCH deficiency occurs when a person inherits a
Currently, there is not a cure for HIBCH deficiency. Children with HIBCH deficiency require a multidisciplinary team of doctors who can assess how the deficiency is affecting each body system and recommend appropriate treatments.
Symptoms
Developmental delay (delayed motor and language skills, low muscle tone, poor feeding in infancy)- Deterioration of neurological functions during the first stages of life
- Vision problems
- Vomiting
Seizures - A blood test showing an increased lactic acid level
- Brain lesions in the basal ganglia
- Accumulation of several valine metabolites in the blood and urine, especially of “3-hydroxy-isobutyryl carnitine”, which is detected as “hydroxy-C4-carnitine” by tandem mass spectrometry (a
screening technique that identify carnitine in blood and urine of children with a suspicion of having an inbornmetabolic disease ).
There are very few cases of HIBCH deficiency described until now. The long term outcome is not well defined yet, but the disease is known to progress (worsen) with time. Severity of HIBCH deficiency does vary. People with the deficiency may have some working
This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.
Medical Terms | Other Names |
Learn More:
HPO ID
|
---|---|---|
80%-99% of people have these symptoms | ||
0001332 | ||
Motor delay | 0001270 | |
Muscular |
Low or weak muscle tone
|
0001252 |
Progressive neurologic deterioration |
Worsening neurological symptoms
|
0002344 |
Vomiting |
Throwing up
|
0002013 |
30%-79% of people have these symptoms | ||
Abnormal vertebral morphology | 0003468 | |
Abnormality of mitochondrial metabolism | 0003287 | |
Aplasia/Hypoplasia of the |
0007370 | |
Epicanthus |
Eye folds
Prominent eye folds
[ more ] |
0000286 |
Facial shape deformation | 0011334 | |
Failure to thrive |
Faltering weight
Weight faltering
[ more ] |
0001508 |
Feeding difficulties |
Feeding problems
Poor feeding
[ more ] |
0011968 |
Hyperreflexia |
Increased reflexes
|
0001347 |
Hypsarrhythmia | 0002521 | |
Increased serum lactate | 0002151 | |
Infantile spasms | 0012469 | |
Metabolic acidosis | 0001942 | |
Involuntary, rapid, rhythmic eye movements
|
0000639 | |
Sleep disturbance |
Difficulty sleeping
Trouble sleeping
[ more ] |
0002360 |
Cross-eyed
Squint
Squint eyes
[ more ] |
0000486 | |
Truncal |
Instability or lack of coordination of central trunk muscles
|
0002078 |
Ventriculomegaly | 0002119 | |
5%-29% of people have these symptoms | ||
Cryptorchidism |
Undescended testes
Undescended testis
[ more ] |
0000028 |
0001298 | ||
Irritability |
Irritable
|
0000737 |
Leukoencephalopathy | 0002352 | |
Respiratory insufficiency |
Respiratory impairment
|
0002093 |
Small basal ganglia | 0012697 | |
1%-4% of people have these symptoms | ||
Head titubation | 0002599 | |
Tetralogy of Fallot | 0001636 | |
Percent of people who have these symptoms is not available through HPO | ||
Abnormal facial shape |
Unusual facial appearance
|
0001999 |
Abnormality of the vertebral column |
Abnormal spine
Abnormal vertebral column
Abnormality of the spine
[ more ] |
0000925 |
Agenesis of corpus callosum | 0001274 | |
Aminoaciduria |
High urine amino acid levels
Increased levels of animo acids in urine
[ more ] |
0003355 |
0000007 | ||
Loss of developmental milestones
Mental deterioration in childhood
[ more ] |
0002376 | |
Dysmetria |
Lack of coordination of movement
|
0001310 |
Generalized hypotonia |
Decreased muscle tone
Low muscle tone
[ more ] |
0001290 |
Global developmental delay | 0001263 | |
Infantile onset |
Onset in first year of life
Onset in infancy
[ more ] |
0003593 |
Myoclonus | 0001336 | |
Seizure | 0001250 |
Cause
Valine catabolism involves several steps with different
HIBCH deficiency is considered an organic acidemia. Organic acidemias are so named because they disrupt amino acid metabolism. This causes an increase in organic acid levels. In HIBCH deficiency we see an increase in lactic acid.
HIBCH deficiency can also be considered a mitochondrial disease, because it disrupts mitochondrial enzymes.
The involvement of the globi pallidi in HIBCH deficiency is one of the main features of the disease. The globi pallidi is part of the basal ganglia in the brain. The reason that the globi pallidi is affected may be due to a failure in providing energy to the brain which results in the early death of brain cells. This finding is also a feature of other mitochondrial diseases (including Leigh
HIBCH is also involved in a second metabolic pathway. This pathway is related to propionate metabolism. Propionate is a substance produced by the break down of some aminoacids. However, the HIBCH gene mutations do not appear to result in adverse symptoms related to this pathway.[2]
Treatment
People with HIBCH deficiency may also benefit from a low-valine diet with carnitine and N-acetyl-cysteine supplementation.[5]
Prompt, supportive, treatment during periods of physical stress and viral illness is vital. This may involve frequent infusions of bicarbonate, plus additional supports as required.[5]
We strongly recommend that these and other treatment options be carefully reviewed with a healthcare provider.
Organizations
Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.
Organizations Supporting this Disease
-
Metabolic Support UK
5 Hilliards Court
Sandpiper Way
Chester Business Park
Chester, CH4 9QP United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: https://www.metabolicsupportuk.org/contact-us
Website: https://www.metabolicsupportuk.org -
Organic Acidemia Association
9040 Duluth Street
Golden Valley, MN 55427
Telephone: 763-559-1797
Fax: 866-539-4060
E-mail: [email protected]
Website: https://www.oaanews.org/ -
Pediatric Brain Foundation
2144 E. Republic Rd.
Building B, Suite 202
Springfield, MO 65804
Telephone: 417-887-4242
E-mail: [email protected]
Website: https://www.pediatricbrainfoundation.org/ -
The Mitochondria Research and Medicine Society
PO Box 55322
BLSC Building, Room # 3-316
Elm and Carlton Streets
Birmingham, AL
Telephone: 716-907-4349
Fax: 716-845-1047
E-mail: [email protected]
Website: https://www.mitoresearch.org
Organizations Providing General Support
-
MitoAction
PO Box 310
Novi, MI 48376
Toll-free: 888-648-6228
E-mail: [email protected]
Website: https://www.mitoaction.org/ -
United Mitochondrial Disease Foundation
8085 Saltsburg Road, Suite 201
Pittsburgh, PA 15239
Toll-free: 1-888-317-8633
Telephone: +1-412-793-8077
Fax: +1-412-793-6477
E-mail: [email protected]
Website: https://www.umdf.org
Learn more
These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.
In-Depth Information
- Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
- Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
References
- Reuter MS & cols. HIBCH deficiency in a patient with phenotypic characteristics of mitochondrial disorders. Am J Med Genet A. 2014; 164A(12):3162-9. https://www.medscape.com/medline/abstract/25251209.
- Petersc H & Ferdinanddussed S, Ruiterd JP & Wandersd RJA. Metabolite studies in HIBCH and ECHS1 defects: Implications for screening. Molecular Genetics and Metabolism. August, 2015; 115 (4):168–173. https://www.sciencedirect.com/science/article/pii/S1096719215300275.
- Jorde LB. Aminoacid Metabolism. In: Kaplan Medical, Inc. Biochemistrhy. USMLE step 1. 2016; 252-253.
- 3-hydroxyisobutryl-CoA hydrolase deficiency. OMIM. 2015; https://www.omim.org/entry/250620.
- Yamada K, Naiki M, Hoshino S et al.,. Clinical and biochemical characterization of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency that causes Leigh-like disease and ketoacidosis. Mol Genet Metab Rep. 2014; 1:455–460. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121361/. Accessed 2/22/2017.
- Brown G K & cols. Beta-hydroxyisobutyryl coenzyme A deacylase deficiency: a defect in valine metabolism associated with physical malformations. Pediatrics. 1982; 70:532-538. https://www.ncbi.nlm.nih.gov/pubmed/7122152.
- What is Mitochondrial Disease?. United Mitochondrial Disease Foundation. https://www.umdf.org/what-is-mitochondrial-disease/. Accessed 2/21/2017.
- Ravenscroft G & cols. Recurrent de novo BICD2 mutation associated with arthrogryposis multiplex congenita and bilateral perisylvian polymicrogyria. Neuromuscul Disord. November, 2016; 26(11):744-748. https://www.ncbi.nlm.nih.gov/pubmed/27751653.
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