Fanconi Syndrome

Fanconi Syndrome: Description, Causes and Risk Factors:Fanconi SyndromeFanconi syndrome is a disorder in which the proximal tubular function of the kidney is impaired, resulting in decreased reabsorption of electrolytes and nutrients back into the bloodstream. Compounds involved include glucose, amino acids, uric acid, phosphate and bicarbonate.The reduced reabsorption of bicarbonate results in type 2 or proximal renal tubular acidosis, which may in some cases exist on its own, or more usually in combination with the Fanconi syndrome.The disease can be be inherited or acquired.Inherited causes:Cystinosis is the most common cause of Fanconi syndrome in children.
  • Other recognised causes of Fanconi's syndrome are Wilson's disease (a genetically inherited condition of copper metabolism), Lowe Syndrome, Tyrosinemia (Type I), galactosemia, glycogen storage diseases, and fructose intolerance.
  • Two forms, Dent's disease and Lowe syndrome, are X linked.
Acquired:It is possible to acquire this disease later on in life. Causes include ingesting expired tetracyclines, and as a side effect of tenofovir in cases of preexisting renal impairment.
  • Lead poisoning also leads to Fanconi Syndrome.
  • Monoclonal gammopathy of undetermined significance can also cause the condition.
In adults, Fanconi syndrome can be caused by various things that damage the kidneys, including:Certain medications, including azathioprine, cidofovir, gentamicin, and tetracycline.
  • Kidney transplant.
  • Light chain deposition disease.
  • Multiple myeloma.
  • Primary amyloidosis.
Most diseases associated with Fanconi syndrome are inherited in an autosomal recessive pattern. Consequently, the child of 2 heterozygous parents, whether male or female, has a 25% chance of being homozygous. The children of an affected individual (homozygous) are all heterozygous and can be affected only if the other parent is heterozygous, a very rare event.Oculocerebrorenal syndrome is transmitted as an X-linked recessive trait, which causes males to be affected more often than females. In oculocerebrorenal syndrome, each daughter has a 50% chance of being a carrier, whereas each son has a 50% chance of inheriting the mutant gene and having the disease. Therefore, in each pregnancy, the female carrier has a 25% chance of having an affected son.The morbidity of Fanconi syndrome is secondary to the metabolic abnormalities it generates. Most of these abnormalities, such as acidosis, calciuria, and phosphaturia, affect bone accretion and, thus, growth. Some forms of Fanconi syndrome, such as cystinosis, lead to renal failure.The incidence of each cause of Fanconi's syndrome is different, although almost all of them are rather rare. Fanconi's syndrome may occur at any age, again according to cause; inherited causes are usually within the first 12 months. Cystinosis occurs almost exclusively in Caucasians. No known racial predilections exist for other forms.Prognosis depends on the cause of the syndrome and the severity of renal and extrarenal manifestations.Symptoms:The clinical features of Fanconi syndrome are:Polyuria, polydipsia and dehydration.
  • Hypophosphatemic rickets (in children) and osteomalacia (in adults).
  • Growth failure.
  • Acidosis.
  • Hypokalemia.
  • Hyperchloremia.
Other features of the generalized proximal tubular dysfunction of the Fanconi syndrome are:Hypophosphatemia/phosphaturia.
  • Glycosuria.
  • Proteinuria/Aminoaciduria.
  • Hyperuricosuria.
Diagnosis:The diagnosis of Fanconi syndrome is made based on tests that document the excessive loss of substances in the urine (eg, amino acids, glucose, phosphate, bicarbonate) in the absence of high plasma concentrations. More elaborate tests are designed to determine the renal threshold for these substances (i.e., the concentration in the blood at which these substances appear in the urine) or their fractional reabsorption (i.e., the percentage of the filtered load that is reabsorbed by the renal tubule). The results are compared with normal levels for age. Recently, an increased urinary lactate-to-creatinine ratio has been postulated as a sensitive test for disordered proximal tubular function.The choice of tests designed to determine the cause of the syndrome should be based on information obtained by means of the history or physical examination. When toxic agents such as drugs or heavy metals are suspected, measure their levels in the blood or urine. When cystinosis appears to be the cause, measure the cellular concentrations of cystine in fibroblasts or leucocytes. Enzymatic defects can be ascertained by measuring tissue levels.Imaging studies do not play an important role in the diagnosis or follow-up of patients with Fanconi syndrome. Rarely, a patient may come to the attention of the physician because of rickets, a consequence of mineral losses in the urine and disturbances in vitamin D metabolism.Most patients with Fanconi syndrome have no distinguishing features of renal morphology. A distortion in the appearance of the proximal tubule, which resembles a swan neck, was described in children with cystinosis and was considered to be the cause of the syndrome. However, this distortion is more likely to be consequence of cellular atrophy secondary to the deposition of cystine. Nonspecific glomerular and tubular changes are also described in Lowe syndrome.Treatment:Management mainly consists of the replacement of substances lost in the urine and specific treatment for the underlying cause.
  • Treat the underlying cause if present. Alkali and potassium for renal tubular acidosis (RTA), phosphate and calcitriol for phosphate wasting.
  • Dehydration due to polyuria: prevent by ensuring adequate fluid intake; episodes of dehydration require either oral or intravenous fluid replacement.
  • Metabolic acidosis due to the loss of bicarbonate: corrected by the administration of alkali - usually sodium bicarbonate.
  • Thiazide diuretic: may be necessary to avoid volume expansion, which increases the excretion of bicarbonate by lowering the renal threshold. However, the diuretic increases potassium loss.
  • Correction of metabolic acidosis is insufficient to treat bone disease, and phosphate and vitamin D supplementation is also required.
  • Phosphate supplements.
  • Vitamin D, given as 1, 25-dihydroxyvitamin D3 or 1a-hydroxyvitamin D3, as liver and/or renal hydroxylation may be impaired in patients with Fanconi's syndrome.
  • Renal losses of glucose, amino acids, and uric acid are not usually symptomatic and do not require replacement.
Preventive Measures:Avoiding exposure to potential toxins, e.g. outdated tetracyclines and aminoglycosides.
  • Effective management of any underlying metabolic disorder, e.g. galactosaemia, tyrosinemia.
NOTE: The above information is for processing purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.

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