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Baker-Winegrad disease

Fructose 1,6 diphosphatase deficiency

Overview

Baker-Winegrad disease is a very rare syndrome caused by a deficiency of the enzyme fructose-1-6-diphosphatase which impairs the body's ability to break down fructose that is consumed in the diet. Fructose 1,6-diphosphatase (FDPase) is a focal enzyme in gluconeogenesis via its conversion of fructose 1,6-diphosphate (FDP) to fructose 6-phosphate (F-6-P), which permits endogenous glucose production from gluconeogenic amino acids, glycerol, or lactate. FDPase deficiency, in turn, results in impaired production of glucose. Glucose is the main type of sugar in the blood and a primary source of energy for the body's cells. Without treatment, affected people can experience hypoglycemia and metabolic acidosis on fasting, episodes of hyperventilation, apnea, and ketosis.

Symptoms - Baker-Winegrad disease

  • Enlarged liver
  • Fasting hypoglycemia
  • Hyperlactacidemic metabolic acidosis

Causes - Baker-Winegrad disease

Baker-Winegrad disease is inherited in an autosomal recessive manner. Inherited mutations in the FBP1 gene cause a deficiency of the enzyme fructose-1,6-bisphosphatase.

Prevention - Baker-Winegrad disease

Avoidance of food that contains fructose prevents the metabolic crisis that results from this disorder.

Diagnosis - Baker-Winegrad disease

The most specific, minimally invasive, diagnostic test for Baker-Winegrad disease is D-fructose challenge; however, this provocative test is dangerous and should be avoided during an acute crisis. In patients with FDPase deficiency, blood glucose levels fall below 60 mg/dL in response to D-fructose challenge, and the serum lactate levels rise (typically >2 standard deviations above the mean).

A prolonged fast can induce lactic acidosis with hypoglycemia in patients with FDPase deficiency as a result of impaired gluconeogenesis.

Challenge with fructose or a fasting study should be performed only under the close supervision of a pediatric endocrinologist or metabolic specialist in an inpatient setting.

Elevated urinary excretion of glycerol-3-phosphate appears to be specific to the disorder. The presence of glyceroluria at or shortly after the time of the metabolic crisis is a useful adjunct to confirm intact lipolytic pathways. However, hyperglyceroluria is not specific because it also can occur in patients with glycerol kinase deficiency.

Direct enzymatic assay of hepatic FDPase activity from hepatic specimens remains the most specific diagnostic test for this disorder. Needle biopsy of the liver may be performed under local anesthesia. Most investigators prefer an open biopsy specimen to guarantee a sample of hepatic tissue sufficient to complete multiple enzymatic analyses.

Prognosis - Baker-Winegrad disease

With prompt diagnosis of this disorder, the prognosis is excellent.

Treatment - Baker-Winegrad disease

This disorder can be treated by complete avoidance of fructose and its related sugars, as well as by avoiding prolonged periods of fasting. Typically, having of small amounts of fructose and related sugars may be tolerated in most patients with fructose-1,6-bisphosphatase deficiency. No other specific medical therapy is generally required.

Patients may only exhibit hepatomegaly during the metabolic crisis, which resolves promptly with administration of dextrose.

Resources - Baker-Winegrad disease

  • NIH
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