HSD17B4-related disorders

What are HSD17B4-related Disorders?

HSD17B4-related disorders are a group of conditions characterized by brain and nervous system abnormalities of varying severity. They are caused by harmful genetic changes (variants) in the HSD17B4 gene. Individuals with HSD17B4-related disorders have abnormally functioning peroxisomes, which are structures within the body's cells necessary for proper metabolism.

HSD17B4-related disorders are associated with a wide range of symptom severity. They include two different conditions: D-bifunctional protein (DBP) deficiency (which has an infantile, juvenile, and adult-onset form) and Perrault syndrome. Many features of juvenile DBP deficiency and Perrault syndrome overlap and it may be difficult to distinguish between the two conditions.

D-bifunctional protein deficiency (Infantile form)

This is the most common form of DBP deficiency. Individuals with this form have poor muscle tone and typically experience seizures shortly after birth or within the first few months of life. They also have significant changes in brain structure, vision and hearing impairment, and severe developmental delays. Few infants with this form achieve any developmental milestones. They may also have liver enlargement and tend to share characteristic facial features.

D-bifunctional protein deficiency (Juvenile form)

Individuals with the juvenile form of DBP deficiency develop symptoms between the ages of 2 and 20. Common features include difficulties with balance and coordination (ataxia), hearing loss, and fertility issues. They may also have nerve damage (neuropathy), vision problems, and developmental delays.

D-bifunctional protein deficiency (Adult-onset form)

The adult-onset form of DBP has similar features as the juvenile form but with symptoms beginning after age 20. Developmental delay is not typically associated with this form.

Perrault syndrome

Individuals with Perrault syndrome have hearing loss that typically begins in early childhood. Those who are XX (typically assigned female at birth) have issues with their ovaries (ovarian dysfunction). This can include absent or underdeveloped ovaries, not starting a menstrual period in adolescence (primary amenorrhea), or early menopause. Most individuals with this condition have additional neurological symptoms, such as difficulties with balance and coordination, developmental delay, and nerve damage.

How common are HSD17B4-related Disorders?

The incidence of DBP deficiency in the population is 1 in 100,000 births.

The exact incidence of Perrault syndrome is unknown. At least 100 families have been diagnosed worldwide.

How are HSD17B4-related Disorders treated?

There is no cure for HSD17B4-related disorders. Treatment is directed at managing the specific symptoms an individual has.  Common interventions for individuals with the infantile form of DBP deficiency may include medications to manage seizures and a feeding tube to ensure adequate nutrition. Individuals with milder forms of DBP deficiency and Perrault syndrome can benefit from assistive devices, such as a walker or wheelchair to assist with mobility or hearing aids. Infertility may be addressed through fertility treatments, such as in vitro fertilization, in some cases.

What is the prognosis for an individual with an HSD17B4-related Disorder?

The prognosis for the infantile form of D-bifunctional protein deficiency is poor. Most children with the condition die within the first two years of life, though occasionally longer survival has been reported. The prognosis for the juvenile and adult-onset forms of DBP deficiency and Perrault syndrome is better. Individuals with these conditions can live well into adulthood. They may require the use of a wheelchair for mobility.