Esotropia, nystagmus and optic disk staphyloma in Donnai-Barrow syndrome / Esotropia, nistagmo e estafiloma de disco óptico na síndrome de Donnai-Barrow

ABSTRACT A 12-year-old boy with Donnai-Barrow syndrome diagnosed intra-uterus presented esotropia, high myopia, nystagmus, and optic disk staphyloma in an ophthalmologic examination. The patient had associated Fanconi syndrome and sensorineural hearing loss as well as facial manifestations as hypertelorism, downward slanting of palpebral fissures and low ear implantation. Magnetic resonance imaging revealed agenesis of the corpus callosum. To our knowledge, this is the first reported case associated with esotropia, nystagmus, and optic disk staphyloma.

RESUMO Paciente do sexo masculino, 12 anos, com diagnóstico intrauterino de síndrome de Donnai-Barrow, apresentava ao exame oftalmológico esotropia, alta miopia, nistagmo e estafiloma de disco óptico. Associado ao quadro, apresentava síndrome de Falconi e perda auditiva neurossensorial, além de alterações faciais, como hipertelorismo, inclinação inferior das fissuras palpebrais e implantação baixa das orelhas. Ressonância magnética revelou agenesia de corpo caloso. Ao nosso conhecimento, este é o primeiro caso relatado associando esotropia, nistagmo e estafiloma de disco óptico.

Multidisciplinary approach for patients with nephropathic cystinosis: model for care in a rare and chronic renal disease / Abordagem multidisciplinar para pacientes com cistinose nefropática: modelo para atendimento em uma doença renal rara e crônica

Abstract Care for patients with chronic and rare diseases is complex, especially considering the lack of knowledge about the disease, which makes early and precise diagnosis difficult, as well as the need for specific tests, sometimes of high complexity and cost. Added to these factors are difficulties in obtaining adequate treatment when available, in raising patient and family awareness about the disease and treatment compliance. Nephropathic cystinosis is among these diseases. After more than 20 years as a care center for these patients, the authors propose a follow-up protocol, which has been used with improvement in the quality of care and consists of a multidisciplinary approach, including care provided by a physician, nurse, psychologist, nutritionist and social worker. In this paper, each field objectively exposes how to address points that involve the stages of diagnosis and its communication with the patient and their relatives or guardians, covering the particularities of the disease and the treatment, the impact on the lives of patients and families, the approach to psychological and social issues and guidelines on medications and diets. This protocol could be adapted to the follow-up of patients with other rare diseases, including those with renal involvement. This proposal is expected to reach the largest number of professionals involved in the follow-up of these patients, strengthening the bases for the creation of a national protocol, observing the particularities of each case.

Resumo A assistência a pacientes com doenças crônicas e raras é complexa, principalmente pela falta de disseminação de conhecimento sobre a doença, o que dificulta o diagnóstico preciso e precoce, além da necessidade da realização de exames específicos, por vezes de alta complexidade e custo. Somam-se a esses fatores dificuldades na obtenção de tratamento adequado quando disponível, na conscientização do paciente e da família sobre a doença e na aderência ao tratamento. A cistinose nefropática está entre essas doenças. Após mais de 20 anos como centro de atendimento a esses pacientes, os autores propõem um protocolo de seguimento, o qual vem sendo empregado com melhora na qualidade da assistência e consiste de uma abordagem multidisciplinar, incluindo, principalmente, atendimento prestado por médico, enfermeiro, psicólogo, nutricionista e assistente social. Neste artigo, cada área expõe de maneira objetiva como abordar pontos que envolvem as etapas do diagnóstico e sua comunicação ao paciente e a seus familiares ou responsáveis, abrangendo as particularidades da doença e do tratamento, o impacto na vida do paciente e de sua família, a abordagem das questões psicológicas e sociais e orientações quanto a medicamentos e dietas. Considera-se que este protocolo poderia ser adaptado ao seguimento de pacientes portadores de outras doenças raras, incluindo aquelas com envolvimento renal. Com essa proposta, espera-se alcançar o maior número de profissionais envolvidos no seguimento desses pacientes, fortalecendo as bases para a criação de um protocolo nacional, observando-se as particularidades de cada caso.

Proximal renal tubular acidosis with and without Fanconi syndrome

Proximal renal tubular acidosis (RTA) is caused by a defect in bicarbonate (HCO₃⁻) reabsorption in the kidney proximal convoluted tubule. It usually manifests as normal anion-gap metabolic acidosis due to HCO₃⁻ wastage. In a normal kidney, the thick ascending limb of Henle’s loop and more distal nephron segments reclaim all of the HCO₃⁻ not absorbed by the proximal tubule. Bicarbonate wastage seen in type II RTA indicates that the proximal tubular defect is severe enough to overwhelm the capacity for HCO₃⁻ reabsorption beyond the proximal tubule. Proximal RTA can occur as an isolated syndrome or with other impairments in proximal tubular functions under the spectrum of Fanconi syndrome. Fanconi syndrome, which is characterized by a defect in proximal tubular reabsorption of glucose, amino acids, uric acid, phosphate, and HCO₃⁻, can occur due to inherited or acquired causes. Primary inherited Fanconi syndrome is caused by a mutation in the sodium-phosphate cotransporter (NaPₐ-II) in the proximal tubule. Recent studies have identified new causes of Fanconi syndrome due to mutations in the EHHADH and the HNF4A genes. Fanconi syndrome can also be one of many manifestations of various inherited systemic diseases, such as cystinosis. Many of the acquired causes of Fanconi syndrome with or without proximal RTA are drug-induced, with the list of causative agents increasing as newer drugs are introduced for clinical use, mainly in the oncology field.

Acute Tubular Necrosis associated with the Ketogenic Diet in a Child with Intractable Epilepsy

The ketogenic diet (KD) has been used as an effective antiepileptic therapy for intractable childhood epilepsy. However, various adverse effects have been reported with use of the KD. We report a case of a child who developed acute tubular necrosis subsequent to therapy with KD. A 5-year-old girl had myoclonic epilepsy with developmental delay. She was under the treatment with antiepileptic drugs since the age of 3 months and on the KD during the past 18 months. Proteinuria persisted intermittently with the initiation of the KD and subsequently increased in the past 2 months. She was admitted with intermittent mild fever, vomiting, and lethargy for the past 3–4 weeks. At the time of admission, she presented with hypertriglyceridemia, heavy proteinuria, renal Fanconi syndrome, and acute kidney injury. Renal sonography showed a marked increase in the size and parenchymal echogenicity of both kidneys. A renal biopsy revealed acute tubular necrosis accompanied by early interstitial fibrosis. After the withdrawal of the KD and supportive therapy, without changing other anticonvulsants and their dosages, improvement of renal function was observed. Proteinuria had disappeared after 1 month and kidney size returned to normal after 8 months. It is hypothesized that the KD can induce and/or aggravate the renal tubulointerstitial injury in some patients who are under the treatment with anticonvulsants.

Tenofovir-induced renal tubular dysfunction among human immunodeficiency virus patients on antiretroviral therapy in Nigeria: Prospects for early detection of presymptomatic nephrotoxicity

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is relatively safe, although renal toxicity has been reported. In Nigeria, there is insufficient data on renal toxicity among patients on TDF. This study assesses TDF-associated tubular dysfunction among human immunodeficiency virus (HIV) patients at a hospital in Nigeria. METHODS: In this cohort study, 104 adult HIV patients were recruited with a simple random technique from the outpatient clinic. Biochemical indices of renal function were estimated from serum and urine at the 16th and 24th week after an initial assessment at baseline. RESULTS: There were no significant differences in baseline proteinuria or glycosuria between TDF and non-TDF groups. Mean baseline urine and serum parameters did not differ significantly between the two groups (P > 0.05). In the TDF group, all urine parameters differed significantly between baseline and 24th week values (P < 0.001). After 16 weeks, mean urine phosphate and urine uric acid increased significantly (P < 0.05) by 2.97 mg/dL and 50.9 mg/dL, respectively, in the TDF group. The rise in mean urine glucose from baseline to the 24th week was more marked in the TDF than the non-TDF group (0.25 vs. 0.07 mmol/L). Higher mean differences in urine albumin were also recorded in the TDF group from baseline to the 24th week. CONCLUSION: Indicators of tubular dysfunction were markedly higher among patients on the TDF-based treatment regimen. Biomarkers of tubular dysfunction could be useful for detecting pre-symptomatic nephrotoxicity before marked reduction of glomerular filtration rate in HIV patients on TDF.

Update of aristolochic acid nephropathy in Korea

BACKGROUND/AIMS: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. METHODS: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. RESULTS: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. CONCLUSIONS: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.

Effects of aristolochic acid I and/or hypokalemia on tubular damage in C57BL/6 rat with aristolochic acid nephropathy

BACKGROUND/AIMS: This study was designed to investigate the roles of aristolochic acid I (AA-I) and hypokalemia in acute aristolochic acid nephropathy (AAN). METHODS: After an adaptation period (1 week), a total of 40 C57BL/6 mice (male, 8 weeks old) were divided into four groups: I (control group), II (low potassium [K] diet), III (normal K diet with administration of AA-I [10 mg/kg weight]), and IV (low K diet with AA-I). After collecting 24 hours of urine at 2 weeks, the mice were sacrificed, and their blood and kidneys were obtained to perform immunochemical staining and/or Western blot analysis. RESULTS: Proteinuria, glycosuria, and increased fractional excretion of sodium and K were prominent in groups III and IV (p < 0.05). Diffuse swelling and poor staining of collecting duct epithelial cells were evident in the medullas of group II. Typical lesions of toxic acute tubular injury were prominent in the cortices of groups III and IV. Α-Smooth muscle actin (α-SMA) was higher in the cortices of the mice in groups III and IV versus group II (p < 0.05), and higher in the medullas of group IV than groups I and III (p < 0.05). E-cadherin was higher in the cortices of groups III and IV compared to group I (p < 0.05). The F4/80 value was higher in the cortices and medullas of groups II, III, and IV compared to group I (p < 0.05), particularly in the case of group II. CONCLUSIONS: AA-I can induce acquired Fanconi syndrome in the acute stage of AAN. Macrophages appear to play a key role in the pathogenesis of AAN and hypokalemic nephropathy. It remains uncertain whether hypokalemia plays any role in AAN and hypokalemia.

An Uncommon Case of Bilateral Pathologic Hip Fractures: Antiviral Drug-induced Osteomalacia in a Patient with Hepatitis B / 대한고관절학회지

The long-term use of adefovir and tenofovir–antiviral medications commonly used to treat chronic hepatitis B–can be associated with proximal renal tubular dysfunction resulting in significant hypophosphatemic osteomalacia. However, there have been few reports about pathological fractures requiring surgical stabilization in cases of antiviral drug-induced hypophosphatemic osteomalacia. We present the case of a 51-year-old man who sustained bilateral pathological hip fractures associated with antiviral drug-induced hypophosphatemic osteomalacia. To treat a lamivudine-resistant hepatitis-B viral infection, the patient received adefovir for 7 years followed by tenofovir for the subsequent 3 years. He had suffered from polyarthralgia and generalized weakness for 2 years prior to presentation at our clinic. Misdiagnosis and inadequate management of his condition accelerated weakness of the bone matrix and ultimately induced pathological fractures. The patient was managed via cementless total hip arthroplasty on the left hip and internal fixation on the right hip. This case highlights that orthopaedic surgeons should consider the possibility of hypophosphatemic osteomalacia if patients receiving antiviral drugs complain of polyarthralgia and generalized weakness.

Adult Idiopathic Renal Fanconi Syndrome: A Case Report

Renal Fanconi syndrome (RFS) is caused by generalized proximal tubular dysfunction and can be divided into hereditary and acquired form. Adult-onset RFS is usually associated with drug toxicity or systemic disorders, and modern molecular genetics may explain the etiology of previous idiopathic cases of RFS. Here, we report the case of a 52-year-old woman with RFS whose etiology could not be identified. She presented with features of phosphaturia, renal glucosuria, aminoaciduria, tubular proteinuria, and proximal renal tubular acidosis. Her family history was unremarkable, and previous medications were nonspecific. Her bone mineral density was compatible with osteoporosis, serum intact parathyroid hormone level was mildly elevated, and 25(OH) vitamin D level was insufficient. Her blood urea nitrogen and serum creatinine levels were 8.4 and 1.19 mg/dL, respectively (estimated glomerular filtration rate, 53 mL/min/1.73 m²). Percutaneous renal biopsy was performed but revealed no specific renal pathology, including mitochondrial morphology. No mutation was detected in EHHADH gene. We propose the possibility of involvement of other genes or molecules in this case of adult RFS.

Adefovir-induced Fanconi syndrome associated with osteomalacia

Fanconi syndrome is a dysfunction of the proximal renal tubules that results in impaired reabsorption and increased urinary loss of phosphate and other solutes. The pathophysiology of drug-induced Fanconi syndrome is unclear. Here we report the case of a 36-year-old woman who presented with pain in multiple bones and proteinuria. She had a 7-year history of taking adefovir at 10 mg/day for chronic hepatitis B. Three years previously she had received surgery for a nontraumatic right femur neck fracture, after which she continued to complain of pain in multiple bones, and proteinuria, glycosuria, and phosphaturia were noted. The findings of a light-microscope examination of a renal biopsy sample were normal, but mitochondrial damage of the proximal tubules was evident in electron microscopy. Western blot analysis revealed that the level of serum fibroblast growth factor 23 (FGF23) was lower than in normal controls. After 2 months of treatment, hypophosphatemia and proximal tubular dysfunction were reversed, and serum FGF23 had normalized. This case suggests that direct mitochondrial damage in proximal tubules can cause drug-induced Fanconi syndrome associated with osteomalacia.

Síndrome de Fanconi y raquitismo hipofosfatémico asociado al uso de tenofovir en una niña infectada con VIH / Tenofovir-associated Fanconi`s syndrome and rickets in a HIV infected girl

El tenofovir (TDF) es un inhibidor de la transcriptasa reversa análogo de nucleótidos, aunque tiene buena tolerabilidad y alta actividad antirretroviral, su efecto sobre el riñón ha sido un motivo de preocupación. Objetivo: Describir el caso de una niña infectada por VIH que presenta síntomas y hallazgos de laboratorio compatibles con un síndrome de Fanconi durante el tratamiento con TDF como parte de su terapia antirretroviral. Caso clínico: Niña infectada por el VIH-1, que después de 18 meses con el tratamiento con TDF presentó pérdida de fuerza y dolor de las extremidades inferiores con deterioro funcional. Los hallazgos de laboratorio fueron compatibles con el síndrome de Fanconi. Las radiografías mostraron fractura bilateral de cadera y muñecas. El síndrome de Fanconi se recuperó por completo cuatro meses después del cambio de terapia antirretroviral. Conclusiones: Los médicos que prescriben TDF deben estar preparados para detectar signos y síntomas indicativos de disfunción renal y considerar de inmediato el cambio del fármaco a otro antirretroviral.

Tenofovir (TDF) is an inhibitor of reverse transcriptase nucleotide analogue, although it has good tolerability and high anti-retroviral activity, its effect on the kidney has been a concern. Objective: To describe a girl infected with HIV who presented Fanconi syndrome during antiretroviral therapy with TDF. Clinical case: We describe a HIV-1-infected girl, who after 18 months treatment with TDF presented loss of strength and pain of the lower extremities with functional impairment. Laboratory findings were consistent with Fanconi syndrome. Radiographs showed bilateral hip fracture and wrists. Full recovery of Fanconi syndrome was achieved four months after changing antiretroviral therapy. Conclusions: TDF-prescribing physicians must be prepared to detect signs and symptoms of renal dysfunction and immediately consider switching to another antiviral drug.

Renal Tubular Acidosis in Patients with Primary Sjögren's Syndrome

Primary Sjögren's syndrome (pSS) is characterized by lymphocytic infiltration of the exocrine glands resulting in decreased saliva and tear production. It uncommonly involves the kidneys in various forms, including tubulointerstitial nephritis, renal tubular acidosis, Fanconi syndrome, and rarely glomerulonephritis. Its clinical symptoms include muscle weakness, periodic paralysis, and bone pain due to metabolic acidosis and electrolyte imbalance. Herein, we describe the cases of two women with pSS whose presenting symptoms involve the kidneys. They had hypokalemia and normal anion gap metabolic acidosis due to distal renal tubular acidosis and positive anti-SS-A and anti-SS-B autoantibodies. Since one of them experienced femoral fracture due to osteomalacia secondary to renal tubular acidosis, an earlier diagnosis of pSS is important in preventing serious complications.

Síndrome de fanconi induzida pelo uso de tenofovir em pessoa coinfectada HIV-hepatite B multirresistente / Fanconi Syndrome induced by the use of Tenofovir in co-infected personHIV-multiresistant Hepatitis B virus

INTRODUÇÃO: A coinfecção vírus da Hepatite B-vírus da imunodeficiência humana (HIV-HBV) é comum e o Tenofovir (TDF) é droga de eleição porque age contra os dois vírus ao mesmo tempo. Porém, em cerca de 1% dos casos pode induzir Síndrome de Fanconi (SF), levando à insuficiência renal. RELATO DE CASO: Em um homem coinfectado HIV-HBV, com a replicação do HIV controlada, o vírus da Hepatite B foi resistente a todos os fármacos disponíveis, exceto ao TDF. Vinte e dois meses após tratamento antirretroviral composto com esse medicamento, o qual controlou a replicação dos dois vírus ao mesmo tempo, desenvolveu insuficiência renal com perda de solutos reabsorvíveis em túbulo contornado proximal, diagnosticada como SF induzida por TDF. Diante do dilema de suspender o TDF para preservar o rim e permitir a replicação do HBV, ou manter o TDF para preservar o fígado e aceitar a degeneração renal, optou-se por balancear o tratamento segundo o melhor equilíbrio possível entre a replicação do HBV e a preservação do rim, ajustando-se a posologia dos medicamentos de acordo com os indicadores clínicos e laboratoriais do risco hepático e do funcionamento renal. CONCLUSÃO: A única possibilidade terapêutica disponível atualmente para pessoas coinfectadas HIV-HBV multirresistente que desenvolvem insuficiência renal por TDF consiste no ajuste da dose do TDF segundo o clearance de creatinina, no tratamento sintomático, na reposição de perdas urinárias com repercussão metabólica e no monitoramento clínico e laboratorial da infecção pelo HIV, da Hepatite B, da insuficiência renal e da remodelação óssea.

INTRODUCTION: HIV-HBV coinfection is common and Tenofovir (TDF) is the drug of choice because it acts against both viruses at the same time. However, about 1% of cases can induce Fanconi Syndrome, leading to kidney failure. CASE REPORT: On an HIV-HBV co-infected man, with controlled HIV replication, Hepatitis B virus was resistant to all available drugs, except TDF. Twenty-two months after antiretroviral treatment compound with that drug, which controlled both viruses? replication at the same time, he developed renal insufficiency with loss of absorbable solutes at proximal convoluted tubule, diagnosed as Fanconi Syndrome induced by TDF. Facing the dilemma of suspending the TDF for preserving the kidney and to allow the replication of the HBV, or to keep the TDF for preserving the liver and to accept the renal degeneration, we chose to balance the treatment according to the best possible equilibrium between HBV replication and kidney preservation, adjusting the posology of medications according to clinical and laboratorial indicators of liver risk and renal function. CONCLUSION: The only therapeutic option currently available to coinfected people by HIV-HBV who develop renal failure by the TDF consists on adjustment of the dose of the TDF according creatinine clearance, symptomatic treatment, replacement ofurinary losses which have metabolic impact, and clinical and laboratory monitoring of the HIV infection, Hepatitis B, Renal insufficiency and Bone remodeling.

A Case of Tenofovir-associated Fanconi Syndrome in Patient with Chronic Hepatitis B / 대한소화기학회지

Tenofovir disoproxil fumarate (TDF) is one of the most widely used treatment options for human immunodeficiency virus (HIV) and HBV infections. Despite its efficacy and safety, some cases of nephrotoxicity have been reported in the treatment of HIV patients. Even more recently, very few cases of Fanconi syndrome associated with tenofovir therapy in HBV monoinfection have been reported. Herein, we report a case of a 47-year-old male with an HBV monoinfection, who developed Fanconi syndrome and a secondary osteomalacia with multiple bone pain. After TDF withdrawal and supplementation of calcitriol, his renal function was reverted. Although the overall risk of TDF-associated nephrotoxicity is very low, both glomerular and tubular function should be monitored in patients undergoing TDF treatment.

Crystalline podocytopathy and tubulopathy without overt glomerular proteinuria in a patient with multiple myeloma

Crystalline nephropathy is a rare yet well-known condition associated with multiple myeloma and other light chain–secreting disorders. Paraproteins that are resistant to proteolysis crystallize within proximal tubular cells and cause light-chain proximal tubulopathy, which presents clinically as Fanconi syndrome. Podocytes are rarely affected, and the crystalline inclusions within podocytes are typically precipitated, yielding significant glomerular proteinuria. Here we report a case of extensive crystalline inclusions primarily within podocytes and proximal tubules that presented only with Fanconi syndrome and renal insufficiency. Despite the presence of extensive crystalline inclusions in podocytes and diffuse foot process effacement, the patient had no clinical evidence suggestive of podocyte injury.

Fanconi Syndrome Associated with Long-term Adefovir and Subsequent Tenofovir Therapy for Chronic Hepatitis B Infection / 대한내과학회지

Adefovir dipivoxil (ADV) and tenofovir disoproxil fumarate (TDF) are nucleotide analogues used to treat chronic hepatitis B (CHB) infection. Nephrotoxicity associated with the use of these medications causes Fanconi syndrome, a rare condition involving generalized dysfunction of the proximal renal tubule causing impaired reabsorption of glucose, uric acid, and phosphate. Fanconi syndrome has been previously reported in patients with human immunodeficiency virus (HIV) or HIV-CHB coinfection treated with other antiretroviral therapies. However, it is rarely reported in patients with CHB monoinfection. We observed a case of Fanconi syndrome in a 61-year-old woman with CHB monoinfection and a history of long-term ADV therapy (42 months), followed by TDF treatment for 9 months. She presented with ankle pain and a tingling sensation in both lower extremities. Laboratory tests revealed hypokalemia, hypocalcemia, hypophosphatemia, hypouricemia, proteinuria, and glycosuria. This case illustrates the importance of recognizing Fanconi syndrome associated with nucleotide analogue treatment and the need to carefully observe symptoms and monitor renal function in these patients.

Pathologic Femoral Neck Fracture Due to Fanconi Syndrome Induced by Adefovir Dipivoxil Therapy for Hepatitis B

In Fanconi syndrome, hypophosphatemic osteomalacia is caused by proximal renal tubule dysfunction which leads to impaired reabsorption of amino acids, glucose, urate, and phosphate. We present a rare case of a 43-year-old Korean male who was found to have insufficiency stress fracture of the femoral neck secondary to osteomalacia due to Fanconi syndrome. He had been receiving low-dose adefovir dipivoxil (ADV, 10 mg/day) for the treatment of chronic hepatitis B virus infection for 7 years and he subsequently developed severe hypophosphatemia and proximal renal tubule dysfunction. The incomplete femoral neck fracture was fixed with multiple cannulated screws to prevent further displacement of the initial fracture. After cessation of ADV and correction of hypophosphatemia with oral phosphorus supplementation, the patient's clinical symptoms, such as bone pain, muscle weakness, and laboratory findings improved.

Pathologic Femoral Neck Fracture Due to Fanconi Syndrome Induced by Adefovir Dipivoxil Therapy for Hepatitis B

In Fanconi syndrome, hypophosphatemic osteomalacia is caused by proximal renal tubule dysfunction which leads to impaired reabsorption of amino acids, glucose, urate, and phosphate. We present a rare case of a 43-year-old Korean male who was found to have insufficiency stress fracture of the femoral neck secondary to osteomalacia due to Fanconi syndrome. He had been receiving low-dose adefovir dipivoxil (ADV, 10 mg/day) for the treatment of chronic hepatitis B virus infection for 7 years and he subsequently developed severe hypophosphatemia and proximal renal tubule dysfunction. The incomplete femoral neck fracture was fixed with multiple cannulated screws to prevent further displacement of the initial fracture. After cessation of ADV and correction of hypophosphatemia with oral phosphorus supplementation, the patient's clinical symptoms, such as bone pain, muscle weakness, and laboratory findings improved.

SLC2A2 gene analysis in three Chinese children with Fanconi-Bickel syndrome / 中国当代儿科杂志

Fanconi-Bickel syndrome (FBS, OMIM 227810), a rare autosomal recessive disorder of carbohydrate metabolism, is caused by SLC2A2 (GLUT2) mutations. The study reported 3 cases of FBS who were confirmly diagnosed by SLC2A2 gene analysis. The three patients showed typical features like glycogen storage disease and proximal renal tubular nephropathy. Homozygous splice-site mutation IVS8+5G>C (c.1068+5 G>C) was found in patient A and homozygous nonsense mutation c.1194T>A (p.Tyr398X) in patient B. Patient C harboured a missense mutation c.380C>A (p.Ala127Asp) and a de novo insertion c.970dupT (p.324TyrfsX392) which was not inherited from her parents. Four mutations were identified in the 3 Chinese FBS patients. Except IVS8+5G>C mutation, the other 3 mutations were novel in Chinese population. To the best of our knowledge, patient C may be the first FBS case worldwide with de novo mutation.