De Toni Debré Fanconi Syndrome

Rare acquired or inherited condition involving a generalized transport defect in the proximal tubules with renal losses of glucose, phosphate, calcium, uric acid, amino acids, and bicarbonates, leading to short stature, osteomalacia, and renal failure.

Lignac De Toni Debré Syndrome; Fanconi Syndrome; Renal Fanconi Syndrome; Fanconi Renal-Tubular Syndrome.

Genetic disorder but also can be caused by inborn errors of metabolism, Wilson disease, Lowe syndrome, cystinosis, glycogenoses, hereditary fructose intolerance, mitochondrial diseases, heavy-metal poisoning, glue sniffing, and toxicity from some chemotherapeutic drugs.

Inherited form is estimated to occur in approximately 1:40,000 live births.

Autosomal dominant, but autosomal recessive and X-linked transmission have been reported. Gene located on 15q15.3.

Syndrome may be inherited (idiopathic familial), secondary to other genetic diseases or secondary to exposure to certain toxins. Cystinosis is the most common genetic cause in childhood. Others are galactosemia, Wilson disease, tyrosinemia, and glycogen storage diseases. Toxins include heavy metals such as cadmium, lead, and mercury, ifosfamide, gentamicin, expired tetracycline, and various solvents. The disease causes failure of proximal renal tubular reabsorption.

Diagnosis is mainly clinical and biochemical. The presenting symptoms are polyuria, polydipsia, and dehydration. The biochemical findings are glucosuria with normal glycemia, hypophosphatemia, hyperaminoaciduria, acidosis, uricosuria, proteinemia, progressive renal insufficiency, and renal sodium and potassium wasting. Following the diagnosis of renal tubular acidosis, an underlying cause should be sought with appropriate investigations for inborn metabolic disease or environmental exposure.

Excessive renal loss of glucose, amino acids, potassium, bicarbonate, phosphate, calcium, water, and magnesium lead to growth retardation/dwarfism, polyuria, polydipsia, metabolic acidosis, muscle weakness, and rickets or osteomalacia (depending on age of onset). De Toni Debré Fanconi syndrome can be the first manifestation of complex IV deficiency.

Assess for dehydration and treat accordingly. Detailed assessment of acid-base and serum electrolyte status is mandatory.

Patients are said to be particularly anxious; consequently, sedative premedication is recommended. Patients have ongoing polyuria and losses of bicarbonate, potassium, phosphate, calcium, and magnesium, which require regular assessment and replacement. It may be appropriate to monitor circulatory volume status during important surgical procedures with the aid of central venous pressure monitoring or monitoring of left ventricular filling. Careful positioning and handling are required because of rickets/osteomalacia.

A case of hyperthermia under general anesthesia in a patient with this syndrome secondary to cystinosis has been reported. After the event, malignant hyperthermia was considered unlikely and pyrexia, which developed during a subsequent nonmalignant hyperthermia-triggering anesthetic, was treated successfully with acetaminophen. Avoid drugs eliminated mainly by the renal system. Remember that some drugs, such as certain antibiotics or neuromuscular relaxant drugs, may require dosage adjustment. Succinylcholine is not contraindicated except in the presence of hyperkaliemia. Uremic patients may be more sensitive to the central depressant effect of benzodiazepines and opioids.

Those associated with renal tubular acidosis:

Periodic Paralysis (PP): Congenital abnormality in membrane electrolyte conductance leading to episodic muscle weakness.

Lightwood Syndrome: Nonhereditary form of primary tubular acidosis presenting with hypercalcemia, hypercalciuria, and nephrocalcinosis.

Albright-Butler Syndrome: Patients present with renal tubular acidosis, nephrocalcinosis, and renal failure. Hypokalemia with muscle weakness and periodic paralysis is frequent. Polyuria, vomiting, and dehydration lead to fluid and electrolyte imbalances.

Adenosine Deaminase Deficiency: Heterogeneous systemic disorder caused by deficiency of adenosine deaminase resulting primarily in severe combined (cellular and humoral) immunodeficiency but also systemic abnormalities.

Gitelman Syndrome: Inherited renal tubular defect resulting in urinary loss of magnesium, sodium, potassium, and chloride with otherwise normal kidneys.

Lowe Syndrome: Genetically transmitted polymalformative syndrome characterized by the association of ocular problems with renal dysfunction and mental retardation.

Phosphoenolpyruvate Carboxykinase Deficiency: Congenital metabolic disease leading to a defect in gluconeogenesis.

Propionic Acidemia: Inborn error of metabolism affecting the mitochondrial catabolism of valine and isoleucine; untreated resulting in ketoacidosis, lethargy, coma, and finally death.

Pyruvate Carboxylase Deficiency: Mitochondrial disease impairing synthetic pathways and leading to hypoglycemia and severe lactic acidosis.

Tyrosinemia: Elevated blood tyrosine levels are present in several clinical entities. The term tyrosinemia is used to describe several syndromes. In general, the association of liver and renal failure, marked edema, epistaxis, and distinctive cabbage-like odor are characteristic of the disease.