Glucose metabolism and insulin secretion in a patient with ABCC8 mutation and Fanconi-Bickel syndrome caused by maternal isodisomy of chromosome 3.
Fanconi-Bickel syndrome (FBS) is a rare disorder of glucose transport caused by autosomal recessive mutations in GLUT2. Clinically, FBS results in growth failure, hepatomegaly, renal Fanconi syndrome, and abnormal glucose homeostasis. We report a 23 month old female with FBS characterized by more severe and refractory hypoglycemia than typically seen in this disorder. Although previous reports indicate that FBS patients have diminished insulin secretion, our patient showed evidence of hyperinsulinism (HI). Sequence analysis showed that the patient was homozygous for a known null mutation in GLUT2, confirming the clinical diagnosis of FBS. Parental genotyping showed that the mother was heterozygous for the GLUT2 mutation, while the father was wild type. Tandem repeat marker analysis showed that the patient inherited the GLUT2 mutation via maternal isodisomy of chromosome 3. Further molecular testing showed that the patient was heterozygous for a mutation in ABCC8, a known cause of congenital HI. We discuss the patient's biochemical responses in light of the molecular findings.
Hoffman
T L
TL
Division of Human Genetics and Birth Defects, Department of Pediatrics, University of California, Irvine, CA 92697-2300, USA. thoffman@uci.edu
Blanco
E
E
Lane
A
A
Galvin-Parton
P
P
Gadi
I
I
Santer
R
R
DeLeón
D
D
Stanley
C
C
Wilson
T A
TA
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D001483:Base Sequence; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000235:genetics; D006008:Glycogen Storage Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007223:Infant; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D009035:Mothers; D009154:Mutation; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors; D013577:Syndrome; D024182:Uniparental Disomy
D018528:ATP-Binding Cassette Transporters; D051273:Glucose Transporter Type 2; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; C495680:SLC2A2 protein, human; D064233:Sulfonylurea Receptors; D005947:Glucose