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Ribose-5-Phosphate Isomerase Deficiency

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Abstract

Natural forces within us are the true healers of disease." " Hippocrates" Indroduction. RPI deficiency. Ribose-5-phosphate isomerase deficiency is a human disorder caused by mutations in the pentose phosphate pathway enzyme ribose-5-phosphate isomerase. With only three diagnosed patients over a 27-year period, RPI deficiency is currently the rarest disease in the world. History of Ribose-5-Phosphate Isomerase Deficiency. In 1999 van der Knaap and colleagues described a 14-year-old boy with developmental delay, insidious psychomotor regression, epilepsy, leukoencephalopathy and abnormal polyol metabolism. Later, Naik and colleagues reported a second case, an 18-year-old man with seizures, psychomotor regression and diffuse white matter abnormality. A third case was reported in 2018 by Sklower Brooks and colleagues, a child with neonatal onset leukoencephalopathy and psychomotor delays. Cause of Ribose-5-Phosphate Isomerase Deficiency. Ribose-5-Phosphate Isomerase Deficiency: New Inborn Error in the Pentose Phosphate Pathway Associated with a Slowly Progressive Leukoencephalopathy.The molecular cause of the pathology is not fully understood. One hypothesis is that ribose-5-phosphate may lack for RNA
Ribose-5-Phosphate Isomerase Deficiency.
Author
Hayk S. Arakelyan. Full Professor in Medicine,
Doctor of Medical Sciences, Ph.D , Grand Ph.D .
Senior Expert of Interactive Clinical Pharmacology , Drug Safety,
Treatment Tactics, General Medicine and Clinical Research.
“Natural forces within us are
the true healers of disease.”
“ Hippocrates”
Indroduction.
RPI deficiency. Ribose-5-phosphate isomerase deficiency is a human disorder
caused by mutations in the pentose phosphate pathway enzyme ribose-5-
phosphate isomerase. With only three diagnosed patients over a 27-year
period, RPI deficiency is currently the rarest disease in the world.
History of Ribose-5-Phosphate Isomerase Deficiency.
In 1999 van der Knaap and colleagues described a 14-year-old boy with
developmental delay, insidious psychomotor regression, epilepsy,
leukoencephalopathy and abnormal polyol metabolism. Later, Naik and
colleagues reported a second case, an 18-year-old man with seizures,
psychomotor regression and diffuse white matter abnormality. A third case was
reported in 2018 by Sklower Brooks and colleagues, a child with neonatal onset
leukoencephalopathy and psychomotor delays.
Cause of Ribose-5-Phosphate Isomerase Deficiency.
Ribose-5-Phosphate Isomerase Deficiency: New
Inborn Error in the Pentose Phosphate Pathway Associated with a Slowly
Progressive Leukoencephalopathy.The molecular cause of the pathology is not
fully understood. One hypothesis is that ribose-5-phosphate may lack for RNA
synthesis; another possibility is that the accumulation of D-ribitol and D-
arabitol may be toxic. n the search for an explanation for this rarity, it has been
found that the patient has a selIdom-seen allelic combination. One allele is a non-
functional null allele, while the other encodes for a partially active enzyme.
Furthermore, the partially functional allele has expression deficits that depend on
the cell type in which it is expressed. Therefore, some of the patient's cells have a
considerable amount of Rpi activity, whereas others do not. RPI deficiency is a
novel inborn error in the PPP. The most likely explanation for the biochemical
abnormalities in our patient is that deficient conversion of ribulose 5-
phosphate into ribose-5-phosphate leads to accumulation of pentoses and
pentose phosphates, which in turn lead to accumulation of ribitol and D-
arabitol as metabolic end products. Ribose-5-phosphate isomerase deficiency
(RPI deficiency) is a human disorder caused by mutations in the pentose phosphate
pathway enzyme ribose-5-phosphate isomerase. With a single diagnosed patient,
RPI deficiency is currently considered to be the rarest disease in the world.
The affected person was a boy born in 1984 and diagnosed by MRI as suffering
from a white matter disease (leukoencephalopathy) . Analysis of SPECT profiles
indicated an increase in the polyols arabitol, ribitol and erithrol. This discovery
later led to the identification of the disease-causing mutations, a premature
stop codon and a missense mutation in the RPI gene. Since the report of this
first case in 1999, no further patients have been diagnosed. In the search for an
explanation for this rarity, it has been found that the patient suffers from a seldom-
seen allelic combination. One allele is a non-functional null allele, while the other
encodes for a partially-active enzyme. Furthermore, the partially-functional allele
has expression deficits that depend on the cell type in which it is expressed.
Therefore, some of the patient’s cells have a considerable amount of RPI activity,
whereas others do not. The molecular cause of the pathology is not fully
understood. One hypothesis is that ribose-5-phosphate may lack for RNA
synthesis; another possibility is that the accumulation of D-ribitol and D-arabitol
may be toxic.
Symptoms of Ribose-5-Phosphate Isomerase Deficiency.
Symptoms include optic atrophy, nystagmus, cerebellar
ataxia, seizures, spasticity, psychomotor
retardation, leukoencephalopathy and global developmental delay. The
disease is clinically characterized by a leukoencephalopathy and mild peripheral
polyneuropathy. The extremely high levels of D-arabitol and ribitol in brain
tissue suggest that the leukoencephalopathy and neuropathy of the patient
may be related to polyol toxicity. This hypothesis is supported by the findings
in two other disorders. In diabetes mellitus and galactosemia, elevated levels
of the polyols . The patient in the present study has leukoencephalopathy, highly
elevated ribitol and D-arabitol levels in his brain and body fluids, and a defect in
the PPP (i.e., RPI deficiency). Recently, we reported on a patient with liver
cirrhosis, abnormal polyol levels in her body fluids, and another defect in the PPP
(i.e., transaldolase deficiency) (Verhoeven et al. 2001). Our findings confirm that
defects involving pentose and polyol metabolism constitute a new area of inborn
metabolic disorders, yet to be explored.
If you have any questions concerningRibose-5-Phosphate Isomerase
Deficiency. , interactive clinical pharmacology , or any other questions, please
inform me .
Prof. Hayk S. Arakelyan
Article
A patient with triosephosphate isomerase deficiency resulting from compound heterozygote mutation is described. Chronic axonal neuropathy was identified on clinical and neurophysiologic grounds and confirmed by sural nerve biopsy. This report describes the first biopsy-proven case confirming that peripheral neuropathy can occur with triosephosphate isomerase deficiency.
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