Fanconi syndrome

This complex contains 11 polypeptide subunits of which only one is encoded by mtDNA. Defects of complex III are relatively uncommon and clinical presentations vary. Fatal infantile encephalomyopathies have been described in which severe neonatal lactic acidosis and hypotonia are present along with generalized amino aciduria, a Fanconi syndrome of renal insufficiency and eventual coma and death. Muscle biopsy findings may be uninformative since abnormal mitochondrial distribution is not seen, i.e., there are no ragged-red fibers. Other patients present with pure myopathy in later life and the existence of tissue-specific subunits in complex III has been suggested since one of these patients was shown to have normal complex 111 activity in lymphocytes and fibroblasts. 

Fatal infantile cytochrome c oxidase (CCO) deficiency is characterized by total absence of catalytic activity in skeletal muscle. This often occurs within the context of the Fanconi syndrome, or less commonly in association with a cardiomyopathy. Although the deficiency is global in skeletal muscle, with all fibers affected, only isolated scattered fibers show abnormal aggregations of mitochondria (ragged-red fibers). Multiple affected siblings within one family are frequently encountered and suggest autosomal recessive inheritance. The condition normally proves fatal before the age of six months and is characterized by worsening intractable lactic acidemia. 

Nephrotoxicity IDV potentially TDF Onset IDV—months after therapy TDF—weeks to months after therapy Symptoms IDV—asymptomatic rarely develop end-stage renal disease TDF—asymptomatic to symptoms of nephrogenic diabetes insipidus, Fanconi syndrome 1. History of renal disease 2. Concomitant use of nephrotoxic drugs Avoid use of other nephrotoxic drugs adequate hydration if on IDV monitor creatinine, urinalysis, serum potassium and phosphorus in patients at risk D/C offending agent, generally reversible supportive care electrolyte replacement as indicated... 

NS (acute) (general population) Renal Aminoaciduria Fanconi syndrome >80 (children) Chisolm 1962 Pueschel et al. 1972... 

Full Fanconi syndrome has been reported to be present in some children with lead encephalopathy (Chisolm 1968 Chisolm et al. 1955). According to the National Academy of Sciences (NAS 1972), the Fanconi syndrome is estimated to occur in approximately one out of three children with encephalopathy and PbB levels of approximately 150 pg/dL. Aminoaciduria occurs at PbB levels >80 pg/dL in children with acute symptomatic lead poisoning (Chisolm 1962). The aminoaciduria and symptoms of lead toxicity disappeared after treatment with chelating agents (Chisolm 1962). 

Cutillas, P.R., Norden, A.G., Cramer, R., Burlingame, A.L., Unwin, RJ. (2003). Detection and analysis of urinary peptides by on-line liquid chromatography and mass spectrometry application to patients with renal Fanconi syndrome. Clin. Sci. (Lond.) 104, 483 490. 

Bl. Baber, M. D., A case of congenital cirrhosis of the liver with renal tubular defects akin to those in the Fanconi syndrome. Arch. Disease Childhood 31, 335-339 (1956). 

Dl. Dent, C. E., The amino aciduria in Fanconi syndrome. A study making extensive use of techniques based on paper partition chromatography. Biochem. J. 41, 240-253 (1947). 

Benign Not evident while sole nutrition is breast milk Severe hypoglycemia and lactic acidosis after fructose ingestion Vomiting, apathy, diarrhea Liver damage and jaundice Proximal renal tubule disorder resembling Fanconi syndrome Treatment eliminate sources of fructose from diet... 

However, one should be aware of the fact that if a particular pharmaceutical is not detected in a WWTP effluent, this does not imply that it has been fully removed. On some occasions, it may have been degraded and give rise to unsuspecting or even more toxic compounds that will subsequently contaminate surface waters [30, 58-60]. As an example, anhydrotetracycline (ATC) and epianhydrote-tracycline (EATC) are tetracycline (TC) degradation products that cause Fanconi syndrome [61]. 

Targeting of nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen could be of interest for the treatment of proteinuria and tubular defects such as Fanconi syndrome and Bartter s syndrome [73,74]. Although a conjugate with an ester spacer is preferred to a conjugate with a direct peptide hnkage [66,67], we continued our research using naproxen di-... 

Renal function impairment Renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported in association with the use of tenofovir. Avoid tenofovir with concurrent or recent use of a nephrotoxic agent. Carefully monitor patients at risk for, or with a history of, renal dysfunction and patients... 

It is indicated in prophylaxis and treatment of rickets, postmenopausal osteoporosis, Fanconi syndrome and hypoparathyroidism. 

Adverse effects are not a major concern with the use of tenofovir. The occurrence of acute renal failure and Fanconi syndrome is rare. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have also been observed. 

Fanconi syndrome (metabolic acidosis secondary to malfunction of proximal renal tubules, resulting in urinary excretion of amino acids, glucose, phosphate, bicarbonate, uric acid, and other substances) secondary to longterm valproic acid has been described in an 8-year-old boy with severe developmental disability (1170). In a review of 10 previous reports of Fanconi syndrome secondary to long-term valproic acid therapy the authors found that all occurred at 4-14 years, all had taken valproic acid for 10 months to 10 years, and symptoms were fully reversible within 2-14 months after withdrawal of valproic acid. Most of the patients (9 of 11) were severely disabled, bedridden, or wheelchair-bound. 

Rosenbaum T. Fanconi syndrome caused by antiepileptic therapy with valproic acid. Epilepsia 2004 45(7) 868-71. 

Mori Y, lesato K, Ueda S, et al. 1984. Renal tubular disturbances induced by tributyl-tin oxide in guinea pigs A secondary Fanconi syndrome. Clin Nephrol 21 118-128. 

Dubois et al. (D24) have made an intensive study of a case of de Toni-Debre-Fanconi syndrome in a 2-year-old child in which there were no cystine deposits they also found an abundant excretion of eitrulline, but no correlation between glycosuria and amino aciduria in the course of a glucose tolerance test (Fig. 4). 

Fig. 4. Chromatogram of a 24-hr urine specimen (sample 1 ml 1,450 ml/24 hr) of a 2-year-old child with de Toni-Debre-Fanconi syndrome (D24). The following features are to be noted. All peaks found in the urine of a normal 2-year-old child are also found here but the peaks here are much higher. In Fig. 3, the sample amounted to 0.625 % of the total 24-hr urine specimen, whereas here it amounts to only 0.07 %. The citrulline peak is a substantial one in the present case, whereas it is absent in normal children.

Excretion of cystine in abnormal amounts can occur in many other cases for instance in cystinosis, the characteristic feature of which is the deposit of cystine crystals in the body tissues, although cystinosis is not always accompanied by excessive excretion of cystine alone in the urine. In de Toni-Debre-Fanconi syndrome there is also an increased cystine output, but this is part of a generalized hyperamino aciduria such as... 

D22. de Toni, G., Renal rickets with phospho-glucoamino renal diabetes (de Toni-Debre-Fanconi Syndrome). Ann. Paediat. 187, 42-80 (1956). 

M3. McCune, D. J., Mason, H. H., and Clarke, H. T., Intractable hypophospha-temic rickets with renal glycosuria and acidosis (the Fanconi syndrome). Report of a case in which increased urinary organic acids were detected and identified, with a review of the literature. Am. J. Diseases Children 66, 81-146 (1943). 

R3. Robson, E. B., and Rose, G. A., The effect of intravenous lysine on the renal clearances of cystine, arginine and ornithine in normal subjects, in patients with cystinuria and Fanconi syndrome and in their relatives. Clin. Sci. 16, 75-93 (1957). 

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