Latent coeliac disease in a child with epilepsy, cerebral calcifications, drug-induced systemic lupus erythematosus and intestinal folic acid malabsorption associated with impairment of folic acid transport across the blood-brain barrier.
A 15-year-old boy with epilepsy and cerebral calcifications, treated with valproic acid, ethyl phenylbarbiturate and ethosuximide, was referred for drug induced systemic lupus erythematosus. Anti-gliadin (AGA) and anti-endomysium (EMA) antibody tests were both positive (EMA titre 1:50). Endoscopic duodenal biopsy showed intense chronic inflammation without villous atrophy or crypt hyperplasia. The child was discharged with a gluten-containing diet. The follow-up showed an increase in EMA titre (1:200) and the persistence of AGA. After 15 months, a second endoscopic intestinal biopsy showed flat mucosa and villous atrophy. Three serum folic acid determinations showed 1.8, 2.4, 2.0 ng/ml (reference range 2.5-16.9 ng/ml) prior to the two intestinal biopsies, but returned to normal levels (11.8 ng/ml) after a gluten-free diet and oral supplementation together. Two years later, the frequency of epileptic seizures was unchanged despite ongoing anti-epileptic treatment and a gluten-free diet. As cerebral calcification and epilepsy are reminiscent of the findings in congenital folate malabsorption, oral loading tests with 5 mg folic acid were carried out and showed impaired intestinal absorption and a defect in the transport across the blood-brain barrier. Low CSF folate levels (13.9 and 12.6 ng/ml, reference range 15-40 ng/ml) and an alteration in the CSF/serum folate ratio (1.43 and 1.16, normal ratio 3:1) were also found as well as increased levels of cystathionine both in CSF (40 micromol/l, reference range 18-28 micromol/l) and in serum (32 micromol/l, reference value <0.10 micromol/l).


CONCLUSIONS
Impairment of intestinal folic acid absorption with a defect in folic acid transport across the blood-brain barrier has been demonstrated in a case of epilepsy and cerebral calcifications associated with coeliac disease.
Calvani
M
M
Division of Paediatrics, San Camillo De Lellis Hospital, Rome, Italy.
Parisi
P
P
Guaitolini
C
C
Parisi
G
G
Paolone
G
G
D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects*; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001927:Brain Diseases / Q000150:complications* / Q000378:metabolism; D002114:Calcinosis / Q000150:complications* / Q000378:metabolism; D002446:Celiac Disease / Q000150:complications* / Q000175:diagnosis* / Q000378:metabolism; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy*; D005013:Ethosuximide / Q000009:adverse effects; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism; D008297:Male; D014508:Urea / Q000009:adverse effects / Q000031:analogs & derivatives; D014635:Valproic Acid / Q000009:adverse effects
D000927:Anticonvulsants; C030251:ethyl phenyl allophanate; D005013:Ethosuximide; D014635:Valproic Acid; D014508:Urea; D005492:Folic Acid