What else is it called?
- 2-methyl-3-hydroxybutyric aciduria
- 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency
- 3-hydroxy-2-methylbutyryl-CoA dehydrogenase deficiency
- 3H2MBD deficiency
- 17β-hydroxysteroid dehydrogenase type 10 deficiency
- HSD10 disease
- Hydroxyacyl-CoA dehydrogenase II deficiency
- MHBD deficiency
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What causes it?
HSD10 deficiency is a rare inherited metabolic disorder in which the body cannot make enough of the HSD10 protein. It is caused by changes in the HSD17B10 gene. The HSD10 protein is located within the mitochondria. Mitochondria are in almost all the cells in our body and are sometimes known as the cell’s batteries as they generate most of the energy that our body needs.
The HSD protein belongs to a larger group of proteins, often called a protein complex. This complex plays a role in making tRNA molecules. The molecules help to make mitochondrial proteins which the body needs to allow it to take energy from the food we eat and change it into a form of energy that the cells in the body can use.
The changes in the HSD17B10 gene mean that there is not enough (a deficiency) of the HSD10 protein, and therefore also the protein complex. This means not enough tRNA molecules are made and so the body cannot produce enough energy. This affects the whole body but especially impacts the parts of the body which uses up most energy, such as the brain, the heart, eyes, and the muscles which is where we see the symptoms of this disorder.
How common is it?
This is a rare disorder with less than 40 reported cases worldwide.
What are the signs and symptoms?
Symptoms are variable in both severity and age of onset. The disorder may present anytime from shortly after birth to early childhood.
Males who are more severely affected may have the following symptoms:
- A loss of previously acquired skills or a loss of previously achieved developmental milestones
- Seizures that are difficult to manage (intractable seizures)
- Involuntary movements characterised by the inability to hold muscles in one position and widespread irregular jerky movements(choreoathetosis).
- A type of cerebral palsy characterised by high muscle tone and stiffness affecting the whole body (spastic quadriplegia/tetraplegia)
- Vision loss due to wasting away of the muscles in the optic nerve – the part of the eye which carries images to the brain (optic atrophy) and/or deterioration of the retina – the layer of nerve cells at the back of the eye which senses light and sends signals to the brain (retinal degeneration).
- Learning difficulties
Some females may have delays in reaching developmental milestones but this is not progressive and they may also have some degree of learning difficulties but otherwise have no other symptoms.
Some males may have a severe form starting in infancy which is characterised by a heart muscle disease (cardiomyopathy). Males with this form may have a poor prognosis with death in early childhood.
Rarely, others present later in childhood with milder symptoms or have no neurological symptoms.
Other symptoms associated with this condition include:
- Speech difficulties (dysarthria)
- Unusual posture affecting balance and walking
- Rhythmic shaking in one or more parts of the body (tremor)
- Involuntary muscle contractions (dystonia)
- A loss of cells in the brain (cerebral atrophy)
- Deafness caused by damage to the inner ear or the auditory nerve (sensorineural deafness)
- Rapid involuntary eye movements (nystagmus)
- Gastrointestinal problems and feeding difficulties
- High levels of lactic acid in the body (lactic acidosis)
How is it diagnosed?
In some countries this disorder can be detected through newborn screening programmes. This is not available in the UK. Diagnosis may be made through specialised blood and urine tests. Diagnosis may be confirmed by genetic analysis.
Can it be treated?
Treatment is focused on managing individual symptoms and providing supportive therapies. A low-protein, high-energy diet with carnitine supplementation may be advised which will be monitored and support provided by a specialist dietitian. Valproic acid should be avoided.
The prognosis is poor, especially for those with the neonatal and infantile forms of the disease. The prognosis for those with milder or no symptoms is unknown.
Do my family need to be tested?
This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males, who have only one X chromosome, a mutation in the only copy of the gene in each cell is sufficient to cause the condition. In females, who have two copies of the X chromosome, one altered copy of the gene in each cell can lead to less severe features of the condition or may cause no signs or symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.