Thiamine(Vitamin B1) | Defective intake | Total parenteral nutrition without B1 supplement1,2 | High plasma lactate | 2–4 mg/d (20 mg in emergency) |
Breast-fed babies from mothers who eat B1-deficient
food; beriberi; Gayet-Wernicke encephalopathy | Urinary
alpha-keto acids (DNPH +) |
Low transketolase in erythrocytes |
Defective binding of coenzyme (TPP) to enzyme
or role of TPP in assisting protein folding: chaperone molecule
? | Maple syrup urine disease (branched-chain α-keto
acid dehydrogenase (see Section 156) | High leucine, isoleucine, valine, alloisoleucine | 20–50 mg/d |
Pyruvate dehydrogenase4 | High lactate, pyruvate; L/P Nl | 20–50 mg/d |
Thiamine transporter THTR-15 | Thiamine-responsive anemia with diabetes and deafness | Megaloblastic anemia | 20–50 mg/d |
No biochemical marker |
DNA testing |
Mitochondrial thiamine | Amish microcephaly | No biochemical marker | Not responsive |
Pyrophosphate transporter6 | DNA testing |
Pyridoxine (VitaminB6) | Defective intake or malabsorption of B6 vitamers | Celiac disease and other malabsorption syndromes | Xanthurenic acid in urines | 8 μg/kg |
Dietary deficiency of vitamin B67 | High threonine, glycine, and serine levels in plasma |
Vitamin metabolism defects: defective metabolism
of pyridoxine, pyridoxal, pyridox(am)ine to its active metabolic
form, pyridoxal phosphate | Pyridox(am)ine phosphate oxidase defect8: neonatal
seizures, myoclonic jerks, burst suppression pattern at EEG, severe
hypotonia, responsive to pyridoxal phosphate (PLP) and not to pyridoxine | LCR: Low HVA, 5HIAA | Pyridoxal-P, 50 mg/d |
High 3-methoxytyrosine and threonine |
Urines: High vanillacetic acid |
Plasma: High glycine, serine, and threonine |
Hypophosphatasia: alkaline phosphatase deficiency | Paradoxically low levels of serum alkaline
phosphatase | Pyridoxal-P, 30 mg/kg |
Tissue nonspecific alkaline phosphatase is required
for the dephosphorylation of PLP to form pyridoxal, which can then
enter the brain and other tissues9,10 (neonatal convulsions with burst suppression on EEG and rickets, or infantile
spasms with hypsarrhythmia) | High PLP and low pyridoxal in plasma | Pyridoxine IV, 100 mg |
Inborn errors causing accumulation of metabolites
and drugs that inactivate PLP | Drugs that affect enzymes involved in B6 vitamer | Hyperhomocysteinemia | 2 mg/kg/d |
Metabolism: enzyme-inducing anticonvulsants,11 methyl
xanthines12 | 50–100 mg/d (preventive) |
Drugs that react with PLP and inactivate it: Hydrazine
(isoniazid) complexes PLP and can induce a peripheral neuropathy
in patients who are slow isoniazid inactivators or who have renal
insufficiency. | 25 mg/day (preventive) |
DL-penicillamine was responsible for symptomatic
B6 deficiency in Wilson patients before DL-penicillamine
was replaced by treatment with D-penicillamine |
Hyperprolinemia type II (delta-1-pyrroline-5-carboxylic
acid [P5C] dehydrogenase deficiency). This block
causes accumulation of P5C that reacts with PLP and inactivates
it.13 | High plasma proline | 50–100 mg/d |
Xanthurenic acid in urines |
Low PLP in plasma |
Pyridoxine-responsive epilepsy (PDE)3,14 (seizures
of perinatal onset refractory to all anticonvulsants, which respond
dramatically to pyridoxine and recur soon after pyridoxine is stopped [see Chapter 558]: delta-1-piperideine-6-carboxylic
acid (P6C), α-amino adipic acid dehydrogenase (ALDH7A1)
is an enzyme of pipecolic acid metabolism that is deficient in PDE
and responsible for the accumulation of P6C that reacts with PLP
and inactivates it. | High pipecolic acid in CSF and plasma α-amino
adipic acid (AASA) in CSF and urines that persists despite B6 treatment | 50–100 mg/d (risks of acute
side effects) |
DNA testing (ALDH7A1) |
Inborn errors affecting PLP-dependent
enzymes (mutations impairing the binding of PLP to the enzyme or
possible role of PLP in assisting protein folding: chaperone molecule ?) | Pyridoxine-responsive anemia (or X-linked
sideroblastic anemia) is caused by a defect in the erythroid-specific
form of delta-aminolevulinate synthase. (Presents in the second
decade of life with a microcytic, hypochromic anemia with a sideroblastic
marrow and other problems caused by iron overload.)15,16 Ninety
percent of patients are B6 responsive. | Enzyme assay in RBC | 100–500 mg/d |
DNA testing |
Classical homocystinuria due to cystathionine β-synthase
deficiency (see Chapter 157). About 50% of
patients are fully or partially responsive. | Total homocysteine > 100 μmol | 200 to 750 mg/d |
Presence of free homocystine |
Methionine > 30 μmol/L |
Ornithine delta-amino transferase deficiency: gyrate atrophy
of the choroid and retina (see Chapter 145).
Only 10% are responsive. | Ornithine > 500 μmol/L in plasma | 500 mg/d |