Ribose-5-phosphate isomerase deficiency
Encyclopedia
Ribose-5-phosphate isomerase deficiency (RPI deficiency,OMIM #608611) 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 thought to be the rarest disease
in the world.
The affected boy was born in 1984 and diagnosed by MRI as suffering from a white matter
disease (leukoencephalopathy
). Analysis of SPECT profiles indicated an increase in the polyol
s 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.
Pentose phosphate pathway
The pentose phosphate pathway is a process that generates NADPH and pentoses . There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH is generated, and the second is the non-oxidative synthesis of 5-carbon sugars...
enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
ribose-5-phosphate isomerase
Ribose-5-phosphate isomerase
Ribose-5-phosphate isomerase is an enzyme that catalyzes the conversion between ribose-5-phosphate and ribulose-5-phosphate .-Structure and catalysis:...
. With a single diagnosed patient, RPI deficiency is currently thought to be the rarest disease
Rare disease
A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...
in the world.
The affected boy was born in 1984 and diagnosed by MRI as suffering from a white matter
White matter
White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
disease (leukoencephalopathy
Leukoencephalopathy
The term Leukoencephalopathy is a broad term for leukodystrophy-like diseases . It is applied to all brain white matter diseases, whether their molecular cause is known or not...
). Analysis of SPECT profiles indicated an increase in the polyol
Polyol
A polyol is an alcohol containing multiple hydroxyl groups. In two technological disciplines the term "polyol" has a special meaning: food science and polymer chemistry.- Polyols in food science :...
s arabitol
Arabitol
Arabitol or arabinitol is a sugar alcohol. It can be formed by the reduction of either arabinose or lyxose. Some organic acid tests check for the presence of D-arabinitol, which may indicate overgrowth of intestinal parasites such as Candida albicans or other yeast/fungus species....
, ribitol
Ribitol
Ribitol or adonitol is a crystalline pentose alcohol formed by the reduction of ribose. It occurs naturally in the plant Adonis vernalis, as well as in the cell walls of Gram positive bacteria . It also contributes to the chemical structure of riboflavin.-External links:**...
and erithrol. This discovery later led to the identification of the disease-causing mutations, a premature stop codon
Stop codon
In the genetic code, a stop codon is a nucleotide triplet within messenger RNA that signals a termination of translation. Proteins are based on polypeptides, which are unique sequences of amino acids. Most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide...
and a missense mutation
Missense mutation
In genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid . This can render the resulting protein nonfunctional...
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
Null allele
A null allele is a mutant copy of a gene that completely lacks that gene's normal function. This can be the result of the complete absence of the gene product at the molecular level, or the expression of a non-functional gene product...
, while the other encodes for a partially-active enzyme. Furthermore, the partially-functional allele has expression deficits that depend on the cell type
Cell type
A cell type is a distinct morphological or functional form of cell. When a cell switches state from one cell type to another, it undergoes cellular differentiation. A list of distinct cell types in the adult human body may include several hundred distinct types.-References:...
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.