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Genetically transmitted metabolic disorder of
carbohydrates characterized by accumulation of glycogen in the liver with
hepatomegaly, proximal tubular nephropathy, fasting hypoglycemia, glucose
(and galactose) intolerance, and dwarfism.
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Hepatorenal Glycogenosis with Renal Fanconi Syndrome;
Hepatic Glycogenosis with Fanconi Nephropathy; Hepatic Glycogenosis with
Aminoaciduria and Glucosuria; Fanconi Syndrome with Intestinal Malabsorption
and Galactose Intolerance; Pseudo-Phlorizin Diabetes; Glycogenosis, Fanconi
type; Glycogen Storage Disease IX; Bickel-Fanconi Syndrome.
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Inborn error of carbohydrate metabolism with tubular
nephropathy. First reported in 1949 by Guido Fanconi, a Swiss pediatrician,
and Horst Bickel, a German physician.
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Approximately 100 cases reported in the literature.
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Autosomal recessive inheritance. Caused by
mutations in the glucose transporter protein 2 (GLUT2 gene) that is
expressed in liver, pancreas, intestine, and kidney. Gene map locus is
3q26.1-q26.3.
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Primary defect of monosaccharide transport across
the membranes. Hyperglycemia (and hypergalactosemia) in the fed state could
be explained by (1) a decreased monosaccharide uptake by the liver or
(2) an inappropriately low insulin secretion caused by impairment of the
glucose-sensing mechanism of the beta cells. Hypoglycemia during fasting may
result from (1) an altered glucose transport out of the liver, resulting in
an increased intracellular glucose level that, in turn, may inhibit glycogen
degradation, leading to glycogen storage and hepatomegaly, or (2) exacerbation
of hypoglycemia due to an increased renal loss of glucose caused by a transport
defect for glucose and galactose across the basolateral membranes of the
proximal tubular cells. As a consequence, renal glycogen accumulation may
occur, with impairment of other functions of the proximal tubular cells and
the characteristic clinical picture of Fanconi nephropathy with
disproportionately severe glucosuria. As a consequence of a transport defect
for glucose and galactose at the basolateral membrane, intestinal
monosaccharide transport also is affected, resulting in malabsorption and
diarrhea.
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Characterized by hepatomegaly. It is caused by hepatorenal
glycogen accumulation, proximal renal tubular dysfunction, and impaired
utilization of glucose and galactose. Glucosuria is considered a most
prominent finding.
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Present in infancy (fever, vomiting, growth
failure, and rickets). Later patients present with dwarfism, protuberant
abdomen, hepatomegaly, moon-shaped face, and fat deposition about the
shoulders and abdomen. Emergence of the teeth and development of puberty are
retarded. Fractures and pancreatitis are complications. Rickets and
osteoporosis later in life are constant features. Glomerular filtration rate
is normal or low normal, and there is no progression to glomerular
insufficiency or deterioration of tubular defects. Polyuria, probably a
result of osmotic diuresis, is a constant finding. Clinical management by
symptomatic replacement treatment (water, electrolytes, and vitamin D,
restriction of galactose, a diabetes mellitus-like diet presented in
frequent small meals with adequate caloric intake). Administration of
uncooked cornstarch has been reported to be beneficial for promoting
growth. Few patients reported still alive in their 50s.
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Preoperative fasting should be kept
as brief as possible and intravenous glucose started to minimize the
possibility of hypoglycemia. Frequent measurement of blood glucose ...