Renales Fanconi-Syndrom

Synonyms: Fanconi's renotubular syndrome

Renal Fanconi syndrome refers to the generalised dysfunction of the proximal tubule. In its isolated form, renal Fanconi syndrome only affects the proximal tubule and not the other nephron segments.¹

Fanconi's syndrome may be inherited or acquired and leads to aminoaciduria, glycosuria, phosphaturia, renal tubular acidosis (RTA) type 2 (proximal), hypophosphataemic rickets (children) or osteomalacia (adults), and renal glycosuria.²³

Epidemiologie

• 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.

• Cystinosis occurs almost exclusively in Caucasians. No known racial predilections exist for other forms.

Ätiologie

Renal Fanconi syndrome is caused by a variety of predominantly rare causes:

Vererbt

• Primary idiopathic: sporadic or familial (autosomal dominant - chromosome 15). Occurs in the absence of any identifiable cause, and most cases are sporadic. Some cases are inherited, but the mode of inheritance appears to be variable (autosomal-dominant, autosomal-recessive, X-linked).⁴

• Secondary: cystinosis, tyrosinaemia, Wilson's disease, Lowe's syndrome (oculo-cerebro-renal syndrome: bilateral congenital cataracts, glaucoma, general hypotonia, hyporeflexia, severe learning disability and Fanconi's syndrome), galactosaemia, fructose intolerance, glycogen storage disorders and mitochondrial cytopathies.

Erworben

• Intrinsic renal disease: acute tubular necrosis, interstitial nephritis, hypokalaemic nephropathy, myeloma, amyloidosis, Sjögren's syndrome, rejected transplant.

• Hyperparathyreoidismus.

• Drugs - eg, cisplatin, ifosfamide, tenofovir, sodium valproate, aminoglycoside antibiotics and deferasirox.⁵

• Toxins: glue sniffing, heavy metals, bee stings.⁶

Präsentation

• Polyuria, polydipsia and episodes of dehydration (sometimes associated with fever).

• Bone deformities: rickets in children or osteomalacia in adults. Result from excessive urinary losses of calcium and phosphate and of a defect in the hydroxylation of 25-hydroxyvitamin D3 into 1,25-dihydroxyvitamin D3.

• Impaired growth and failure to thrive.

Differentialdiagnose

• Andere Ursachen von polyuria und polydipsia - eg, Diabetes mellitus, diabetes insipidus.

• Andere Ursachen von rickets and osteomalacia.

• Andere Ursachen von Gedeihstörung und Kurzstatur.

Untersuchungen

• The diagnosis is based on excessive loss of substances in the urine (eg, amino acids, glucose, phosphate, bicarbonate) in the absence of high plasma concentrations.

• Further investigations are required to identify the cause.

• Proteinurie: usually, however, only in small quantities.

• Hypokaliämie, Hypophosphatämie und hyperchloraemic metabolic acidosis.

Behandlung

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 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. 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.

Komplikationen

• Morbidity and complications are secondary to the underlying and resulting metabolic abnormalities.

• Most abnormalities (eg, acidosis, calciuria, and phosphaturia) affect bone development and therefore growth.

• Some forms of Fanconi's syndrome (eg, cystinosis) lead to chronische Nierenerkrankung.

Prognose

Prognosis depends on the cause of the syndrome and the severity of renal and extrarenal manifestations.

Prävention

• Avoiding exposure to potential toxins - eg, outdated tetracyclines and aminoglycosides.

• Effective management of any underlying metabolic disorder - eg, galactosaemia, tyrosinaemia.