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Special Feature
November 2000

Pathological Case of the Month

Author Affiliations
 

ENIDGILBERT-BARNESSMD

Arch Pediatr Adolesc Med. 2000;154(11):1165. doi:
Diagnosis and Discussion: Glycogen Storage Disease With Renal Tubular Dysfunction (Type XI, Fanconi-Bickel Syndrome)

Figure 1. The patient is unable to stand up because of pain. She is short for her age, and there is bowing in her legs.

Figure 2. Radiographs of the patient's extremities show osteoporosis and severe rickets.

Figure 3. Results of liver needle aspiration biopsy show glycogen accumulation (hematoxylin-eosin, original magnification ×200).

Fanconi-Bickel syndrome is a rare type of glycogen storage disease first described by Fanconi and Bickel in 1949.1 It is an autosomal recessive disease for which an enzymatic defect has not yet been identified. The disease is characterized by the association of a large liver with massive glycogen accumulation and severe renal tubular dysfunction.2 Renal Fanconi syndrome, characterized by urinary loss of phosphate, amino acids, glucose, and bicarbonate, results in severe hypophosphatemic rickets and markedly stunted growth.3

Affected children usually present in the first year of life with failure to thrive. A protuberant abdomen with hepatomegaly and enlarged kidneys are noticeable by age 2 years.4 These children develop severe hypophosphatemic rickets early in life unless they receive oral phosphate supplementation. Orally administering phosphate alone to the extent necessary for correction of hypophosphatemia may heal the florid rickets, but adequate growth is not attained. At adolescence these children have an extremely short stature. After puberty the hepatomegaly may recede although hepatic glycogen concentration remains increased. Some patients have additional muscular involvement.5

Proximal renal tubular dysfunction with glucosuria, phosphaturia, generalized aminoaciduria, bicarbonate wasting, and hypophosphatemia are characteristic findings. Serum alkaline phosphatase levels are increased, and there are radiological findings of rickets. Mild fasting hypoglycemia and hyperlipidemia may be present, but these are not consistent findings. Uric acid levels are low. Liver transaminases and plasma lactate are usually normal. Results of tissue biopsy show marked accumulation of glycogen in the hepatocytes and proximal renal tubular cells.

There is no known enzyme deficiency. All measured hepatic glycolytic enzyme activities are normal. Oral galactose tolerance tests typically show galactose intolerance, suggesting an impairment of galactose metabolism. Defective galactose oxidation can be demonstrated in vitro in fresh minced liver tissue and fibroblasts, despite normal activities of hepatic galactokinase, uridyltransferase, and uridyl di phospho–glucose 4-epimerase in homogenates of frozen liver.6

There is no specific therapy. Symptomatic replacement of water, electrolytes, vitamin D, and phosphate, restriction of galactose intake, and adequate caloric intake may improve growth. Long-term prognosis is not known.

References
1.
Fanconi  GBickel  H Die chronishe aminoacidurie (Aminosaure-diabetes oder nephrotisch-glucosurisher zwergwuchs) bei der glykogenese und der cystinkrankheit. Helv Paediatr Acta. 1949;4359
2.
Sokol  PJ Inborn errors of metabolism. Roy  CCSilverman  AAlagille  Deds.Pediatric Clinical Gastroenterology 4th ed. St Louis, Mo Mosby Year–Book Inc1995;812- 876
3.
Kliegman  RM Defects in metabolism of carbohydrates. Behrman  REKliegman  RMArvin  AMeds.Nelson Textbook of Pediatrics 15th ed. Philadelphia, Pa WB Saunders Co1996;385- 397
4.
Chen  YTBurchell  A Glycogen storage diseases. Scriver  CRBauded  ALSly  WSValce  Deds.The Metabolic and Molecular Basis of Inherited Disease New York, NY7th ed. McGraw Hill1995;935- 965
5.
Hurvitz  HElpeleg  ONBarash  V  et al.  Glycogen storage disease, Fanconi nephropathy, abnormal galactose metabolism and mitochondrial myopathy. Eur J Pediatr. 1989;14948- 51Article
6.
Brivet  MMoatti  NCorriat  ALemormier  AOdievre  M Defective galactose oxidation in a patient with glycogen storage disease and Fanconi syndrome. Pediatr Res. 1983;17157- 161Article
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