HSD10 disease is a disorder that affects the nervous system, vision, and heart. It is typically more severe in males than in females. Most affected males have a form of HSD10 disease in which early development seems normal, followed by a stage in which affected individuals rapidly lose skills they have acquired. This developmental regression often occurs between the ages of 1 and 2 and results in severe intellectual disability and loss of communication skills and motor skills such as sitting, standing, and walking. This form of the disorder is referred to as the infantile type. Less commonly, affected males have severe neurological problems from birth and never develop motor skills. This form is called the neonatal type. Males with the infantile or neonatal type frequently have weak muscle tone (hypotonia), recurrent seizures (epilepsy), and vision loss that gradually gets worse. Weakening of the heart muscle (cardiomyopathy) also occurs and is a common cause of death in males with severe HSD10 disease. Many affected males do not survive beyond early childhood.

Females with HSD10 disease may have developmental delay, learning problems, or intellectual disability, but they do not experience developmental regression. Some affected females have additional features of this condition, such as epilepsy, movement problems, and hearing loss. Affected females appear to have a normal life expectancy.

HSD10 disease is caused by mutations in the HSD17B10 gene, which provides instructions for making the HSD10 protein. This protein is located within mitochondria, the energy-producing centers inside cells, where it is involved in the production (synthesis) of proteins. While most protein synthesis occurs in the fluid surrounding the nucleus (cytoplasm), a few proteins are synthesized in the mitochondria.

During protein synthesis, in either the mitochondria or the cytoplasm, molecules called transfer RNAs (tRNAs) help assemble protein building blocks (amino acids) into chains that form proteins. The HSD10 protein is part of a group of proteins (a complex) that is involved in making functional mitochondrial tRNA molecules, which aid in the synthesis of mitochondrial proteins. Normal mitochondrial protein production is essential for the formation of the groups of proteins that convert the energy from food into a form cells can use.

The HSD17B10 gene mutations that cause HSD10 disease reduce the amount of HSD10 protein in cells, impair their structure or function, or both, which leads to a deficiency of the functional complex in which it plays a part. This deficiency impairs the production of mitochondrial tRNAs. Without enough tRNAs, the mitochondrial synthesis of proteins involved in cellular energy production is reduced. A shortage of these proteins results in insufficient energy production in cells of the brain, eyes, and heart, leading to the characteristic features of HSD10 disease.

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.

Signs of HSD10 disease typically begin between 9 and 14 months of age. The condition tends to be more severe in boys than girls.

Signs of the condition in boys may include the following:

• Trouble with muscle movement
• No longer being able to do things they could do before (milestone regression)
• Loss of motor skills
• Floppy arms and legs (hypotonia)
• Vision loss
• Heart problems
• Seizures (epilepsy)

Signs of the condition in girls may include the following:

• Developmental delays
• Seizures (epilepsy)

Newborn screening for HSD10 disease is done using a small amount of blood collected from your baby’s heel. During screening, a special machine measures how much of certain substances (called acylcarnitines) are in your baby’s blood. The body produces these substances when it breaks down food. Babies with high levels of these substances might have HSD10 disease.

What Happens After an Out-of-Range Screening Result?

If your baby’s blood spot screening result for HSD10 disease is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.

An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing. An out-of-range result can mean that your baby has one of several possible conditions. It is important to do follow-up testing to correctly identify the condition causing your baby’s result.

Your baby may need the following tests after an out-of-range screening result:

• Blood and/or urine tests
• Genetic testing using a blood sample: this is the only way this condition can be diagnosed

You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems if they are not diagnosed and treated quickly.

False-positive newborn screening results for this condition are rare. Babies who are born early (premature) may have out-of-range results.

Some babies may have a false-positive result for HSD10 disease because their mother has high acylcarnitine levels. These babies do not have and will not develop HSD10 disease. More testing on both mom and baby will determine who has high acylcarnitine levels.

Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.

It is important to talk to your health care provider about how to best care for your baby. Currently, the treatment options available cannot stop the progression of the condition. Health care providers will develop a plan that is tailored to the needs of each child.

Management may include:

• Diet low in certain proteins
• Regular and frequent meals and snacks