NORD gratefully acknowledges Wendy Chung, MD PhD, Clinical and Molecular Geneticist, Kennedy Family Professor of Pediatrics and Medicine, Columbia University Medical Center, and the DHPS Foundation, for the preparation of this report.
Deoxyhypusine synthase (DHPS) disorder is a rare disorder characterized by neurodevelopmental delay and seizures beginning in childhood. This autosomal recessive genetic condition is caused by changes (mutations) in the DHPS gene.
Mutations in the DHPS gene are thought to be responsible for the following:
DHPS disorder is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
DHPS disorder is caused by changes (mutations) in the DHPS gene. The DHPS gene is responsible for production of the deoxyhypusine synthase enzyme that is involved in the synthesis of an unusual amino acid called hypusine. This aminio acid is found in only a single protein, eukaryotypic translation initiation factor-5A (EIF5A). EIF5A promotes translation, elongation, or production of many proteins in the body.
Several individuals with two different mutations in DHPS gene have been identified.
Two siblings have both been diagnosed with c.888 +1 G>A mutation and p.N131S. Another child has been diagnosed with c.912_917delTTACAT, p.Y305_I306del and p.N131S. The fact that all three children share the p.N131S mutation with a loss of function mutation suggests that it is extremely likely that this is the correct diagnosis.
Studies have shown that the c.888 +1 G>A mutation results in abnormal splicing of the DHPS gene and leads to loss of function of that copy of the DHPS gene.
The p.Tyr305_Ile306del mutation present in the third child also leads to loss of function of the DHPS gene.
The p.N131S mutation leads to greatly decreased DHPS enzyme activity but not complete loss of function.
A diagnosis of DHPS disorder is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. Children with mild or moderate intellectual disability and speech development problems, but no other anomalies may be suspected of having DHPS disorder. A diagnosis is confirmed through molecular genetic testing for mutations in the DHPS gene.
Clinical Testing and Workup
Molecular genetic testing can detect disease-causing variations in the DHPS gene, but is available only as a diagnostic service at specialized laboratories. Doctors will take a blood sample of individuals suspected of having a DHPS disorder and the sample will undergo whole exome sequencing (WES). WES is a molecular genetic testing method that examines the genes in humans that contain instructions for creating proteins (protein-encoding genes). This is called the exome. WES can detect variations in the DHPS gene that are known to cause disease, or variations in other genes known to cause symptoms similar to this disorder.
Affected individuals may undergo additional tests before molecular genetic testing to rule other conditions, or after molecular genetic testing to assess the extent of the disease. An advanced imaging (x-ray) technique called magnetic resonance imaging (MRI) may be recommended. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues including the brain.
Neurologic examination is important for individuals with the symptoms of DHPS disorder. Neurologic examination helps identify the specific features affecting a person. Laboratory tests, neurophysiologic testing, and neuroimaging; routine laboratory studies (such as blood counts, serum electrolytes, and tests of kidney, liver, and endocrine functions); and analysis of cerebrospinal fluid (obtained by “spinal tap”) may be conducted to help exclude alternate and co-existing diagnoses.
The treatment of DHPS disorder is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who specialize in diagnosing and treating disorders of the brain and central nervous system in children (pediatric neurologists) and adults (neurologists), speech therapists, physical therapists, occupational therapists, and other healthcare professionals may need to systematically and comprehensively plan treatment.
There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients.
Following an initial diagnosis, a developmental assessment may be performed and appropriate occupational, physical, and speech therapies be instituted. Speech therapy is required and can include one-on-one sessions with a speech therapist, combined sessions where children learn language and social skills as a group, and the use of augmentative and alternative communication (AAC). AAC includes the use of communication devices, both high tech and low tech ones, that can help children express thoughts, wants, needs and ideas.
Periodic reassessments and adjustment of services should be provided with all children. Additional medical, social, and/or vocational services including specialized learning programs may be necessary.
Genetic counseling is recommended for affected individuals and their families. Psychosocial support for the entire family is essential as well.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
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Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For more information about clinical trials conducted in Europe, contact:
DHPS Genecard https://www.genecards.org/cgi-bin/carddisp.pl?gene=DHPS&keywords=dhps Accessed March 18, 2019.
DHPS Foundation. Literature Review. http://www.dhpsfoundation.org/dhps/literature-review/ Accessed March 18, 2019.
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