Ribose-5-phosphate isomerase (RPI) deficiency is a very rare genetic disorder caused by mutations in an enzyme of the hexose monophosphate shunt called the ribose-5-phosphate isomerase. The first case of RPI deficiency was detected in the year 1999 by van der Knaap and team, where they found a 14-year old boy suffering from developmental delay, leukoencephalopathy, seizure, psychomotor retardation, and irregular polyol metabolism because of a frameshift mutation in one allele. The second case was reported afterward by Naik and fellow workers in an 18-year old boy, who was suffering from similar symptoms as the first case but with a novel homozygous missense mutation and diffuse white matter abnormality. Whereas the third case was detected recently in 2018 by Brooks and colleagues in a newly-born child with severe psychomotor regression and leukoencephalopathy. Hence with only 3 diagnosed cases, RPID is known as the world’s second rarest disease.
Defining RPI –
RPI is a highly conserved protein that exists in two forms namely, RpiA and RpiB, and is found in both prokaryotic and eukaryotic cells. It acts as an enzyme and helps ribose-5-phosphate (R5P) to get converted into ribulose-5-phosphate (Ru5P). The review shows the need of RpiA which has a significant influence in the Calvin cycle in plants and the pentose phosphate pathway (PPP) in both plants and animal creatures. RPI plays an important role in the production of nucleotides and cofactors from R5P in the PPP and Calvin cycle.
RPI deficient patients have been found to have a rare allelic union, where one of the alleles is non-functional (null allele) and the other allele is partially active. Here, the partially functional allele has a shortage of gene expression thus few patients suffer from a substantial amount of RPI activity. Some postulate suggests that enzyme assays in cultured fibroblast homogenates prove that R5P may be deficient for RNA synthesis to occur or it can be also caused due to the secretion of D-arabitol (sugar alcohol) and D-ribitol (pentose alcohol), which are revealed by the Proton magnetic resonance spectroscopy of the brain. We still don’t have any understanding of the molecular cause of this particular disease.
Here are some of the symptoms that have been reported in a R5P isomerase deficient patient :-
Optic Atrophy: Damage and death of the nerve cells of the eyes causing vision loss.
Cerebellar Ataxia: Uncoordinated muscular movement due to damage in the cerebellum.
Seizures: Disorder in the nerve cell of the brain causing an uncontrolled electrical disturbance in the function of the brain.
Spasticity: Altered muscular performance causing muscle stiffness and tightness.
Leukoencephalopathy: Disease of the white matter of brain bot molecular and non-molecular.
Nystagmus: Involuntary movement of the eye which is also known as ‘dancing eye.
Developmental delay: Disorder that is found in the developmental stages of children that causes a delay in speech, cognition, fine motor, and daily life activities.
Psychomotor retardation: Slowing down of emotional, physical activity, and speech.
Currently, there is no prognosis or treatment for this rare disease. But some of its symptoms can be improved in the following ways :
Optic Atrophy: There is no treatment for this disease, but if it is diagnosed during the early stages, it can help prevent further damage from the disease. Thus, regular eye check-up is necessary.
Cerebellar Ataxia: Episodic ataxia can often be controlled with a drug named as acetazolamide and by changing the lifestyle pattern. Likewise, Acquired ataxia can be dealt with relying upon the particular reason like by giving anti-microbial or antiviral medicines that might help assuming it’s caused by some infection.
Seizures: The diagnosis is based on symptoms, physical signs and test results such as an EEG, CT or CAT scan or MRI. Treatment includes antiepileptic medications (AEDs), weight-reduction plan and abscission.
Spasticity: Spasticity can be decreased by performing stretching exercises daily and using splinting, casting, and bracing so that the motion and flexibility are maintained.
Leukoencephalopathy: Treatment includes removing any drugs that is affecting the immune system.
Nystagmus: Nystagmus can be hereditary, but it can also be a sign of another medical condition. Thus a regular eye exam and appointment with an optometrist is recommended to determine the cause and course of action.
It would be great if we can develop certain treatments for the patients suffering from this rare disease. But we have some biotechnology companies that have accelerated their efforts for finding a cure for the rarest diseases. The names of those companies are as follows:
- Alexion Pharmaceuticals : Alexion Pharmaceuticals, a part of AstraZeneca, that specializes in orphan drugs to treat rare diseases.
- NPS Pharmaceuticals : NPS pharma recently approved short bowel syndrome and Recombinant human parathyroid hormone drugs, such as Gattex and Natpara respectively.
- Aegerion Pharmaceuticals : Aegerion’s came up with a pill to treat homozygous familial hypercholesterolemia or HoFH, known as Juxtapid.
- BioMarin Pharmaceuticals : BioMarin’s research is based on enzyme replacement therapies (ERTs). It was the first company to provide therapeutics for phenylketonuria (PKU) by manufacturing Kuvan and Firdapse. BioMarin has also provided therapeutics for mucopolysaccharidosis type I (MPS I), by manufacturing laronidase (Aldurazyme), that was commercialized by Genzyme Corporation.
- ViroPharma : Thispharmaceutical company develops and sell drugs that addressed serious diseases. The main focus of the company is on product development activities like on viruses and human disease, including those caused by hepatitis C virus (HCV) and cytomegalovirus (CMV) infections.
Souhrid Sarkar is an Aspiring Biotechnologist. He is a B.Tech student at Amity University Kolkata. He is content writer at BioXone. He is a Research Intern at Indian Institute of Technology, Bombay (IITB) & Reviewer at TMR Publishing Group. He is Keyboardist by hobby.