Laboratory Studies
Serum pyridoxal 5'-phosphate (PLP) is the primary active pyridoxal form and is used as the primary index of whole-body pyridoxal levels.
Albumin level should be measured with serum PLP, as PLP levels are dependent on albumin levels so PLP levels can be falsely interpreted as low if the albumin level is not taken into account. [19]
Levels of 4-pyridoxic acid can be measured in the urine. [16] This compound is the major inactive metabolite of pyridoxine metabolism and its levels normally are 128-680 nmol per nmol of creatinine. Excretion of this compound reflects the pyridoxine body pool in the absence of an exogenous pyridoxine load. Urine levels of 4-pyridoxic acid are lower in females than in males and will be reduced in persons with riboflavin deficiency. Neither age nor alcohol intake affects the measured level.
Erythrocyte aspartate aminotransferase (EAST) and the EAST activation coefficient (EAST-AC) are long-term indicators of functional pyridoxine status due to the 120-day life span of erythrocytes. EAST-AC reduction lags behind the onset of the pyridoxine deficiency. Thus, a low EAST-AC value confirms a subacute to chronic deficiency state. Chronic alcoholism causes these indexes to be falsely low; in addition, these indexes decrease with age. Hemolytic anemia reduces the life span of erythrocytes.
Conversion of tryptophan to niacin relies on pyridoxine-dependent enzymes. A tryptophan load of 50-100 mg/kg is administered, and the urinary excretion of tryptophan metabolites is measured. High excretion of kynurenine, kynurenic acid, and xanthurenic acid indicates a functional deficiency in pyridoxine-dependent enzymes. This test is influenced by protein intake, exercise, lean body mass, and pregnancy. Hormonal factors and infections enhance tryptophan-to-niacin conversion. Thus, this test is most useful for monitoring an individual's response to pyridoxine supplementation rather than for diagnosing a deficiency.
If arteriosclerosis is present, the homocysteine level should be measured. [18]
Hematologic indexes may indicate the presence of a hypochromic-microcytic anemia with normal iron levels. Patients with inherited sideroblastic anemias have marked red blood cell dimorphism, anisocytosis, and poikilocytosis.
Elevation in urinary α-aminoadipic semialdehyde and serum or CSF pipecolic acid are nonspecific biomarkers for pyridoxine dependent seizures. Additionally, the ALDH7A1 gene can be sequenced. [7]
Other Tests
Electroencephalogram findings in neonates and infants with pyridoxine-dependent seizures are characterized by repetitive runs of high-voltage, generalized, bilateral, synchronous 1- to 4-Hz spikes and sharp wave bursts.
Normalizing electroencephalogram findings or causing clinical cessation of seizures by injecting 100 mg of intravenous pyridoxine identifies pyridoxine-dependent and pyridoxine-responsive seizures.
