PEDBASE.org - The Pediatric Database - Detailed information of HEREDITARY FRUCTOSE INTOLERANCE

HEREDITARY FRUCTOSE INTOLERANCE

DEFINITION:

A disorder of fructose metabolism characterized by a deficiency of 1-phosphofructaldolase activity resulting in hepatic and renal manifestations.

EPIDEMIOLOGY:

incidence: 1/40/000
age of onset:
- whenever fructose-containing foods are introduced into the diet
risk factors:
- familial - autosomal recessive
  - chrom.#: 9q22
  - gene: 1-phosphofructaldolase
- M = F

PATHOGENESIS:

1. Background

1-phosphofructaldolase catalyzes the conversion of fructose-1-phosphate to glyceraldehyde and dehydroxyacetone-phosphate - sucrose disaccharide -> glucose and fructose
- may be used in baby foods and formulas

2. Genetic Defect

genetic defect -> deficiency of 1-phosphofructaldolase activity (almost complete in the liver) -> fructose-1-phosphate accumulates in hepatocytes producing progressive liver disease and in the proximal tubules resulting in Fanconi Syndrome - some affected patients also have a reduced hepatic capacity to convert fructose-1,6-diphosphate into glyceraldehyde-3-P and dihydroxyacetone phosphate

CLINICAL FEATURES:

1. Hepatic Manifestations

diaphoresis, irritability, tremors, seizures (hypoglycemia)
lethargy -> coma
jaundice, hepatomegaly,
progressive liver disease

2. Fanconi Syndrome

episodes of vomiting, dehydration, weakness, & unexplained fever
anorexia, constipation
polydipsia and polyuria
failure to thrive and growth failure
rickets

INVESTIGATIONS:

1. Urine

positive for reducing substances (fructosuria)
- positive Clinitest but negative Clinistix indicates that the reducing substance is not glucose
fructose identified by chromatography

2. Serum

conjugated hyperbilirubinemia
elevated transaminases with progressive liver disease

3. Liver Biopsy

progressive fatty infiltration and fibrosis
focal cytoplasmic dissolution
abnormal appearance of glycogen and mitochondria
plate-like and needle-like crystals in hepatocytes

4. Fructose Tolerance Test

contraindicated because fructose-1-phosphate is competitive with glucose-1-phosphate for phosphorylase and therefore a sudden load of fructose-1-P will interfere with the conversion of glycogen to glucose -> sudden hypoglycemia -> shock -> death

5. Fanconi Syndrome

1. Serum

normal anion gap hyperchloremic metabolic acidosis (with low serum bicarbonate)
normal or low amino acids
normal glucose
hypophosphatemia, hypokalemia, hypouricemia
elevated alkaline phosphatase

2. Urine

generalized (non-specific) hyperaminoaciduria
glucosuria, phosphaturia
pH < 5.5 with low specific gravity (hyposthenuria)
bicarbonaturia, hyperkaliuria, uricosuria, tubular protein-uria, carnitinuria, low urinary ammonia

3. Imaging Studies

1. Skeletal X-Ray

rickets, osteopenia, or osteoporosis

MANAGEMENT:

1. Diet

eliminate fructose and sucrose from the diet
prognosis is poor with death in infancy or early childhood if diet is poorly controlled
prognosis is guarded in some patients even with good dietary control

2. Fanconi Syndrome

manage underlying disorder

Pediatric Database - HEREDITARY FRUCTOSE INTOLERANCE

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