PEDBASE.org - The Pediatric Database - Detailed information of FRUCTOSE-1,6-DIPHOSPHATASE DEFICIENCY

FRUCTOSE-1,6-DIPHOSPHATASE DEFICIENCY

DEFINITION:

A disorder of gluconeogenesis characterized by a deficiency of fructose-1,6-diphosphatase activity resulting in hepatomegaly and a lactic acidosis.

EPIDEMIOLOGY:

incidence: ?
age of onset:
- whenever fructose or sucrose is introduced into the diet
risk factors:
- familial - autosomal recessive
  - chrom.#: ?
  - gene: fructose-1,6-diphosphatase

PATHOGENESIS:

1. Background

fructose-1,6-diphosphatase catalyzes the conversion of fructose-1,6-diphosphate to fructose-6-phosphate and is one of the four key enzymes of gluconeogenesis

2. Genetic Defect

genetic defect -> deficiency of fructose-1,6-diphosphatase -> with introduction of fructose or sucrose-containing formulas or foods -> hyperlacticacidemia -> attacks of hypoglycemia and/ or shock, seizures, coma, and death
attacks precipitated by:
- ingestion of fructose- or sucrose-containing foods or formulas
- fasting for >10 hrs
- fructose, glycerol, or alanine tolerance tests

CLINICAL FEATURES:

1. Neurological Manifestations

with ingestion of sucrose or fructose, develop attacks of:
- lethargy -> coma
- infantile hypotonia
- neonatal seizures
psychomotor retardation

2. Other Manifestations

shock
hepatomegaly only sign between attacks

INVESTIGATIONS:

1. Serum

wide anion gap metabolic acidosis due to a lactic acidosis
hypoglycemia
hyperlipidemia, hyperuricemia

2. Liver Biopsy

fatty infiltration
elevated lipid content (accounts for hepatomegaly)
reduced glycogen content (<1.5% of wet liver weight [N=2-6%])

3. Glucose Tolerance Tests

Glucagon - no rise in blood glucose
Galactose - produces normal increase in blood glucose
Fructose, Glycerol, Alanine
- contraindicated in this disorder as each may precipitate an attack

4. Diagnosis

deficiency of fructose-1,6-diphosphatase activity in liver biopsy samples

MANAGEMENT:

1. Supportive

a chronic disease with a life-long risk of episodes of hypoglycemia and thus must:
- provide long-term follow-up
- moniter serum glucose levels
- coordinate a multidisciplinary approach:
  - Paediatrics, Neurology, Metabolics, Dietary, Genetics
- plan for acute episodes

2. Goals of Therapy

symptomatic control of and avoidance of acute episodes
not curative

3. Diet

1. For Acute Episodes

IV D10W infusion

2. Chronic

high carbohydrate diet (56%)
- exclude fructose, sucrose, and sorbitol from the diet
low protein diet (12%)
normal to low fat diet (32%)
may need to provide sufficient calories via an intragastric infusion system

4. Prognosis

with early and good dietary control normal growth & development
with poor dietary control psychomotor retardation and/or death

Pediatric Database - FRUCTOSE-1,6-DIPHOSPHATASE DEFICIENCY

Pediatric Organization - Pedbase [at] Gmail.com