What are the other Names for this Condition? (Also known as/Synonyms)

• 17 Beta-Hydroxysteroid Dehydrogenase Type 10 Deficiency Disorder
• 2M3HBA (2-Methyl-3-Hydroxybutyric Aciduria)
• 2-Methyl-3-Hydroxybutyryl-CoA Dehydrogenase Deficiency Disorder

What is 2-Methyl-3-Hydroxybutyric Aciduria? (Definition/Background Information)

• 2-Methyl-3-Hydroxybutyric Aciduria (2M3HBA) is an inherited disorder in which the body cannot effectively process the amino acid isoleucine
• Signs and symptoms of this condition usually develop in infancy or early childhood and include metabolic acidosis, hypoglycemia, hypotonia, seizures, movement problems, retinal degeneration, and hearing loss
• Affected males have severe neurodegeneration with loss of developmental milestones, whereas females have mild to moderate developmental delay
• 2-Methyl-3-Hydroxybutyric Aciduria is caused by mutations in the HSD17B10 gene; it has an X-linked dominant pattern of inheritance

(Source: 2-Methyl-3-Hydroxybutyric Aciduria; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets 2-Methyl-3-Hydroxybutyric Aciduria? (Age and Sex Distribution)

• 2-Methyl-3-Hydroxybutyric Aciduria is a rare congenital disorder. The presentation of symptoms may occur in infancy or early childhood
• The disorder can occur in both genders. However, generally males have more severe symptoms than females
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for 2-Methyl-3-Hydroxybutyric Aciduria? (Predisposing Factors)

• A positive family history may be an important risk factor, since 2-Methyl-3-Hydroxybutyric Aciduria is an inherited condition
• Currently, no other risk factors have been clearly identified for the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of 2-Methyl-3-Hydroxybutyric Aciduria? (Etiology)

• 2-Methyl-3-Hydroxybutyric Aciduria is caused by mutations in the HSD17B10 gene
• This gene codes for the HSD10 protein, which is involved in the assembly of functional transfer RNA (tRNA) inside mitochondria
• Mutations in the HSD17B10 gene are inherited in a X-linked dominant manner

X-linked dominant inheritance pattern: In this type of inheritance, the defective gene is carried on the X chromosome. A single copy of the defective gene in each cell of an individual is sufficient for the disease to manifest itself. Since males have only one X chromosome inherited from their mother, the defective gene is expressed in them, causing the condition. Although females carry two X chromosomes, the unaffected gene copy in the normal X chromosome does not completely mask the effects of a defective gene copy

What are the Signs and Symptoms of 2-Methyl-3-Hydroxybutyric Aciduria?

The signs and symptoms of 2-Methyl-3-Hydroxybutyric Aciduria may include:

• Aggressive behavior
• Agitation
• Cerebral cortical atrophy 
• Choreoathetosis 
• Delayed speech and language development
• Developmental regression
• Dysarthria
• Generalized hypotonia
• Global developmental delay 
• Hypertrophic cardiomyopathy 
• Hypoglycemia
• Intellectual disability
• Lactic acidosis 
• Metabolic acidosis 
• Nystagmus 
• Optic atrophy 
• Retinal degeneration 
• Seizures
• Sensorineural hearing impairment 
• Spastic tetraplegia 
• Visual loss

(Source: 2-Methyl-3-Hydroxybutyric Aciduria; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

The following may also be noted in some individuals:

• Cardiomyopathy
• Developmental regression

How is 2-Methyl-3-Hydroxybutyric Aciduria Diagnosed?

2-Methyl-3-Hydroxybutyric Aciduria is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of 2-Methyl-3-Hydroxybutyric Aciduria?

The potential complications of 2-Methyl-3-Hydroxybutyric Aciduria may include:

• Hearing loss
• Permanent loss of vision
• Progressive neurologic deterioration 
• Problems with coordination and movement 
• Risk of falls and injury due to epileptic episodes
• Cardiomyopathy, which may lead to heart failure

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is 2-Methyl-3-Hydroxybutyric Aciduria Treated?

There is no cure for 2-Methyl-3-Hydroxybutyric Aciduria, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops

How can 2-Methyl-3-Hydroxybutyric Aciduria be Prevented?

2-Methyl-3-Hydroxybutyric Aciduria may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of 2-Methyl-3-Hydroxybutyric Aciduria? (Outcomes/Resolutions)

• The prognosis of 2-Methyl-3-Hydroxybutyric Aciduria is poor in males, many of whom succumb to the disorder by early childhood
• Females with the condition may exhibit mild-to-moderate signs and symptoms. However, the life expectancy is reported to be normal in affected females

Additional and Relevant Useful Information for 2-Methyl-3-Hydroxybutyric Aciduria:

2-Methyl-3-Hydroxybutyric Aciduria is also known by the following additional synonyms:

• 3H2MBD Deficiency Disorder
• 3-Hydroxy-2-Methylbutyryl-CoA Dehydrogenase Deficiency Disorder
• HSD10 Deficiency Disorder
• HSD10 Disease
• Hydroxyacyl-CoA Dehydrogenase II Deficiency Disorder
• MHBD Deficiency Disorder

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/