Clinical Information

Polyols are sugar alcohols that have been identified in blood, urine, and cerebrospinal fluid. Characteristic patterns of abnormal polyols may suggest a disorder of the pentose phosphate pathway (PPP), including transaldolase (TALDO) deficiency, transketolase, and ribose-5-phosphate isomerase (RPI) deficiency. The PPP is involved in carbohydrate metabolism and is present in the cytosol of all cells. Two specific functions of the PPP are the production of nicotinamide adenine dinucleotide phosphate (NADPH[+]) and the synthesis of ribose-5-phosphate, a molecule necessary for nucleotide and nucleic acid synthesis. TALDO, transketolase, and RPI deficiency, which have multisystem involvement are recently described disorders of this pathway. Sedoheptulokinase deficiency is also recently described but it’s correlation to disease is unclear as only two unrelated patients from consanguineous families been reported to date. These 2 patients had different multisystem involvement.(1)

Transaldolase deficiency is an autosomal recessive disorder caused by a reduction of the enzyme transaldolase. Clinical manifestations are characterized by severe neonatal liver failure, coagulopathy, low serum protein, hypoglycemia, high ammonia, progressive myocardial hypertrophy, and abnormal lactate dehydrogenase with remarkably normal or low transaminases.

Patients may present in the antenatal period with maternal HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), hydrops fetalis and oligohydramnios, dysmorphic features, cutis laxa, and hypertrichosis. The clinical course is variable, but acute liver failure with normal transaminases is a common finding. Initially, hepatomegaly is absent, but the spleen may be enlarged. Later, hepatomegaly with liver cirrhosis and mild kidney failure occurs.

Ribose-5-phosphate isomerase deficiency is an autosomal recessive disorder caused by a deficiency of the enzyme ribose-5-phosphate isomerase. Clinical manifestations include neurological deficits such as slow progressing leukoencephalopathy and neuropathy. Additionally, spasticity, ataxia, epilepsy, regression, and delayed psychomotor development have been described.

Transketolase deficiency is an autosomal recessive disorder characterized by short stature, developmental delay, and congenital heart defects. Dependent on thiamine, transketolase is directly involved in the branch of the pathway that channels excess sugar phosphates to glycolysis.(2) Characteristic polyol patterns in both urine and plasma include elevations of arabitol/xylitol, ribitol, and erythritol. Transketolase deficiency is caused by deleterious biallelic variants in TKT.

Sedoheptulokinase deficiency is an autosomal recessive condition characterized by increased excretion of erythritol and sedoheptulose.(3) Relationship to disease is yet unclear as only 2 patients have been described in the literature.

Polyols analysis in urine is the method of choice for the biochemical diagnosis of TALDO, transketolase, and RPI deficiency. Abnormal results should be followed with either enzymatic or molecular genetic analysis.