Diagnosis Of Primary Hyperoxaluria Research Articles

Late onset primary hyperoxaluria after kidney transplantation in a 36-year-old woman

Primary hyperoxaluria is a rare congenital autosomal recessive disorder disrupting the glyoxylate metabolism pathway in the liver. Type1 primary hyperoxaluria is caused by a deficiency in a specific liver enzyme namely, alanine glyoxylate-aminotransferase which catalyzes the conversion of glyoxylate to glycine. By the absence of this enzyme, glyoxylate is converted to oxalate and high oxalate level causes deposition of insoluble calcium oxalate crystals in different organs specifically kidneys. The disease usually manifested by recurrent nephrolithiasis and/or nephrocalcinosis leads to renal failure. This report describes an end-stage renal disease case of a 36-year-old Iranian woman without any history of nephrolithiasis who underwent kidney transplantation. She developed an early onset transplant kidney failure. The patient underwent kidney biopsy, which revealed oxalate nephropathy, accordingly the genetic study confirmed diagnosis of primary hyperoxaluria. This rare case shows how type 1 primary hyperoxaluria can develop after kidney transplantation without having any manifestation prior to transplantation

Adolescente e straniero in un “mondo” di adulti

L'iperossaluria primaria di tipo 1 è causata da mutazioni nel gene codificante per l'enzima L-alanina-gliossilato amino transferasi (AGT), che è espresso nel fegato. La trasmissione avviene con modalità autosomica recessiva: i genitori sono portatori sani della mutazione (e spesso non sanno di averla, soprattutto se non ci sono familiari affetti), mentre ciascun figlio della coppia ha il 25% di probabilità di essere malato. Esiste anche un secondo tipo della malattia (iperossaluria primaria di tipo 2), causato dalla carenza di un altro enzima, la D-glicerato deidrogenasi, e un terzo tipo (iperossaluria di tipo 3), identificato piú di recente e causato dal difetto del gene DHDPSL. Sulla base dell'osservazione clinica ed eventualmente della storia familiare, la diagnosi di iperossaluria primaria può essere formulata grazie a test di laboratorio (misurazione dell'ossalato di calcio nelle urine e nel sangue) e analisi genetica, con ricerca delle mutazioni nel gene coinvolto. La diagnosi e il trattamento precoci sono in grado di ridurre il rischio di evoluzione verso l'IRC e verso complicanze gravi come l'ossalosi sistemica. L'articolo riguarda un caso clinico che ha coinvolto il gruppo infermieristico che ha modificato l'approccio e la presa in carico di un adolescente in un “mondo” di adulti. (sian) (nursing)

Primary hyperoxaluria detected by bone marrow biopsy: case report

BackgroundPrimary hyperoxaluria is a rare disease with an estimated prevalence of 1 to 3 cases per million. It is due to a hepatic enzyme deficiency responsible for an endogenous overproduction of oxalate. Oxalate crystals commonly deposit in the kidney and more rarely in bone marrow.The literature has reported, to the best of our knowledge, only two cases of hyperoxaluria diagnosed by bone marrow biopsy and our case is the only one that does not show radiological bone lesions.Case presentationA young 22 year old chronic hemodialysis patient with nephrocalcinosis. The patient had a personal and family history of recurrent kidney stones. He presented bone pain with worsening of his general state. On physical examination, no organomegaly was detected. Biological check-up showed only a normochromic and normocytic regenerative anemia resistant to treatment and a bone marrow biopsy was performed. It showed deposits of crystals of oxalate in the bone marrow surrounded by inflammatory reaction against foreign bodies. Given our context, no liver biopsy or genetic studies, which are gold standard of diagnosis testing, were done. The diagnosis of primary hyperoxaluria was made based on morphological characteristics of crystals, his medical and family history, and the absence of any secondary cause of the condition. Since curative treatment is not available in our country, the patient only receives a palliative treatment.ConclusionPrimary hyperoxaluria is rarely evoked by the histological study of a bone marrow biopsy. The lack of the possibility of the only effective treatment in our context and the diagnosis, usually late, of this pathology are at the origin of the fatal evolution of the disease in almost all the cases.

Abstract 19245: Heart of Stone: A Mysterious Case of Diastolic Dysfunction

A 27 year old Somali female initially presented with renal failure and a creatinine of 10mg/dl. A kidney biopsy showed crystalline nephropathy and she was initiated on hemodialysis. A year later while she was pregnant she had multiple heart failure admissions. Echocardiograms (echo) showed normal ejection fraction (EF). A month after delivery she was admitted again with heart failure. Vital signs were stable with elevated JVP and a pansystolic murmur at the apex. Chest x ray showed pulmonary edema. Echo showed moderately concentric left ventricular hypertrophy (LVH) with an EF of 40% and severe mitral regurgitation (MR). Doppler echo showed restrictive filling pattern. Pulmonary artery pressure (PA) was 99 mm of Hg + right atrial pressure (RA) with dilated vena cava. Repeat echocardiogram post ultrafiltration of just 1 liter of volume reduced PA pressures from 99 mm+RA to about 35 mm Hg+ RA with a simultaneous reduction in MR, demonstrating marked preload dependency of left sided filing pressures. Her myocardium demonstrated an echodense speckled reflection and infiltrative cardiomyopathy was suspected. EKG showed LVH making amyloidosis unlikely diagnosis. Right ventricular endomyocardial biopsy showed extensive deposition of calcium oxalate crystals in myocardium. Further tests showed increased serum oxalate level: 140 μmoles/L (ref. upto 27), increased urinary oxalic acid excretion:171 μgm (ref. < 57) and increased urine glycolate: 101 μg/mg Cr (ref. < 79) . Liver biopsy showed very low AGT (Alanine glyoxylate aminotransferase) activity of 3.0 μmol/h/mg protein (Ref. 19.1-47.9) along with negative AGT immunoreactivity . These results confirmed diagnosis of primary hyperoxaluria type 1 (PH1) . She was started on intense hemodialysis regimen and underwent a deceased donor combined liver-kidney transplantation (CLKT). Repeat echo 6 months later shows normal EF, normal PA pressures, regression of infiltrative process with improvement in diastolic function. This is a rare case of PH1 with cardiac involvement leading to progressive infiltrative restrictive cardiomyopathy and recurrent heart failure. Early recognition of the disease is important because CLKT may achieve long-term survival and regression of cardiomyopathy.

Stony kidneys in a child: Clue to a rare diagnosis

alanine-glyoxalate transaminase. Type 2 is caused by the deficiency of cytosolic enzymes glyoxalate reductase and D-glycerate dehydrogenase. Type 3 results from a primary increase in the absorption of oxalate from the gastrointestinal tract.Classic presentation is nephrocalcinosis with nephrolithiasis, which leads to renal failure in early adulthood. Once the kidneys fail, oxalate accumulates in the body and gets deposited at various sites. Preferred A five-year-old boy presented to the Emergency Department with altered sensorium. He had nausea, with occasional vomiting and anorexia for the past one week. His parents denied any history of fever, diarrhea or a significant past medical history or significant family history. The child was unconscious, afebrile, with a pulse rate of 68/minute, blood pressure of 140/80 mmHg and respiratory rate of 17/minute. The systemic examination was unremarkable.Urinalysis showed calcium oxalate crystals in abundance and blood investigations revealed elevated urea and creatinine levels. A twenty-four hour urinary oxalate was found to be elevated.Abdominal radiographs showed bilateral diffusely dense kidneys [Figure 1]. Ultrasonography revealed normal-sized kidneys with a smooth outline and uniformly raised cortical echogenicity. No calculus or hydronephrosis was present. Non-contrast computed tomography (NCCT) showed diffusely increased density of both the kidneys with calculi in the gall bladder [Figure 2]. Based on the findings of urinalysis and imaging characteristics, a diagnosis of primary hyperoxaluria was suspected and later confirmed on liver biopsy.Primary hyperoxaluria is a group of autosomal recessive disorders caused by deficient metabolism of glyoxalate to glycine, leading to an increased production of oxalate that gets deposited in various organs. At least three different types of hyperoxalurias are known.

Primary hyperoxaluria causing ESRD and gangrene of extremities leading to amputation

Primary hyperoxaluria is an uncommon, inherited metabolic disorder due to hepatic enzyme deficiencies with consequent hepatic oxalate overproduction and attendant systemic complications. The diagnosis is established on a combination of clinical parameters, elevated urinary excretion of oxalate and glycolate and determination of alanine glyoxylate aminotransferase in the liver tissue. We describe a 45-year-old female with end-stage renal disease secondary to nephrolithiasis, who presented with a fulminating vascular syndrome before confirming the diagnosis of primary hyperoxaluria. This case illustrates that in this infrequent clinical entity, the diagnosis is often delayed with incorrect initial management.

Leukoerythroblastic anemia due to oxalosis with extensive bone marrow involvement

A 27-year-old North African immigrant man was admitted because of bone pain and discomfort. Since he arrived to Spain, 2 years before, he presented bilateral nephrocalcinosis in an abdomen X-ray, and a progressive renal failure of unknown etiology that required hemodialysis and a renal transplant. The post-transplant course was complicated and required transplantectomy and hemodyalisis. The histological study revealed plenty of oxalate crystal deposition and the diagnosis of oxalosis was made. Amount of oxalate was determined to be 306 lmol/L and glycolate was 73.6 lmol/L in hemodialytic filtrate, consistent with diagnosis of primary hyperoxaluria. Two years after transplantectomy, leukopenia and anemia were detected. The physical examination was normal. The main hematological parameters were: hemoglobin 73 g/L, reticulocytes 71.2 3 10/L, white blood cell count 3.3 3 10/L (59% neutrophils, 34% lymphocytes, 6% monocytes, 1% eosinophils), and platelet count 194 3 10/L. The serum levels of sodium was 139 mmol/L, potassium 6 mmol/L, urea 25.9 mmol/L, and creatinine 731 lmol/L. A peripheralblood smear showed anisocytosis with numerous teardrop forms and a leucoerythroblastic anemia, that led to a bone marrow aspirate and trephine biopsy. The bone marrow aspirate resulted dry tap and only scarce material was obtained from the needle, showing some giant cells and few crystals (Image 1). The trephine biopsy showed an extensive deposition of polarizable oxalate crystals with moderate fibrosis and abundant foreign body giant cells without recognizable residual hematopoiesis (Image 2). The patient underwent a combined liver and kidney transplantation. He presented a hyperacute renal rejection and died 2months later because of splenic and portal vein thrombosis. Primary hiperoxaluria is a very infrequent metabolic disorder secondary to the lack of alanineglioxylate aminotransferase, which rapidly develops to renal failure. However, it has been reported to be more frequent among people from Canary Islands and north of Africa.

Primary hyperoxaluria in a 27-year-old woman

Primary hyperoxaluria is a rare autosomal recessive disorder resulting in precipitation of insoluble oxalate crystals in the joints, kidneys, heart, eyes, and skin. Two thirds of patients have calcium oxalate nephrolithiasis by age 5 years and 80% die of renal failure by age 20 years. Rarely, the disease will present in adulthood, with the onset of symptoms occurring as late as the sixth decade. We present a 27-year-old woman with end-stage renal disease who presented to the dermatology department for the evaluation of a reticular rash shortly after beginning peritoneal dialysis. Associated symptoms included arthralgias and episodic acral cyanosis. Previous kidney and skin biopsy specimens revealed crystalline deposition, however, the diagnosis of primary hyperoxaluria was not entertained until an atrial mass was found to have the same crystalline material. This report reviews primary hyperoxaluria and underscores the importance of recognizing the disease as a cause of renal failure in a patient with livedo reticularis and skin lesions resembling calciphylaxis. Early recognition of the disease is important because combined liver-kidney transplantation may achieve long-term survival.

Genetic analysis ? a diagnostic tool for primary hyperoxaluria type I

Primary hyperoxaluria type I is an autosomal recessive metabolic disease in which excessive oxalates are formed by the liver and excreted by the kidneys, causing a wide spectrum of disease, ranging from renal failure in infancy to mere renal stones in late adulthood. The diagnosis may be suspected when clinical signs and increased urinary oxalate and glycolate excretion present, and is confirmed by the measurement of decreased alanine:glyoxylate aminotransferase activity in a liver sample. The enzymatic assay is not readily available to pediatric nephrologists in many parts of the world. We describe three families from Croatia in whom the diagnosis of primary hyperoxaluria was solely based on clinical findings that included nephrolithiasis and nephrocalcinosis accompanied by increased urinary oxalates and glycolate excretion, as enzymatic assays of liver samples could not be performed. Mutation analysis of the AGXT gene encoding the defective enzyme confirmed the diagnosis, revealing three alleles carrying the C156ins mutation and two the G630A mutation. Screening first-degree relatives for the relevant mutation disclosed an asymptomatic affected sibling. Mutation analysis of the AGXT gene is a non-invasive and accurate tool for the diagnosis of type I primary hyperoxaluria that may replace enzymatic assays of liver biopsies.

Primary hyperoxaluria: Report of a patient with livedo reticularis and digital infarcts

Primary hyperoxaluria encompasses 3 rare genetic disorders of glyoxylate metabolism characterized by excessive urinary excretion of oxalic acid, resulting in oxalosis. Patients typically have recurrent calcium oxalate nephrolithiasis and nephrocalcinosis, leading to chronic renal failure and death from uremia. Oxalate can deposit in extrarenal sites such as the heart, walls of arteries and veins, bone, and skin. We report a patient who presented with acute renal failure and later experienced livedo reticularis and peripheral gangrene before the diagnosis of primary hyperoxaluria was established. A skin biopsy specimen demonstrated numerous characteristic elongate to diamond-shaped, radially oriented, pale yellow translucent oxalate crystals within the vessels, and vessel walls of the subcutaneous fat that were strongly birefringent under polarized light. (J Am Acad Dermatol 2002;46:S16-8.)

Simultaneous Determination of Oxalate, Glycolate, Citrate, and Sulfate from Dried Urine Filter Paper Spots in a Pediatric Population

Measurement of oxalate in urine is important for the diagnosis of primary hyperoxaluria (McKusick 259900) and the secondary forms produced by excessive intake or abnormal intestinal absorption of oxalate (1). Determination of glycolic acid is essential for the diagnosis of primary hyperoxaluria type 1. Finally, to estimate the risk of stone formation in calcium oxalate urolithiasis and nephrocalcinosis, simultaneous determination not only of calcium but also of citrate (a potent inhibitor of calcium oxalate and calcium phosphate crystallization) and other constituents (electrolytes, phosphate and sulfate) is required to calculate urinary calcium saturation (2). Ion-chromatography HPLC (3)(4) and specific enzymatic assays (5)(6) are available only in specialized laboratories. In addition, preservation and storage of liquid samples may influence the stability of oxalate and glycolate (7). Use of urinary filter spots is a practical alternative for the collection and safe transport of samples to be analyzed for many metabolic disorders. To evaluate the age-related changes of oxalate, glycolate, citrate, and sulfate in a pediatric population, we developed an automated ion-chromatography system for the simultaneous measurement of these anions in urine and established their reference values for liquid urine samples as well as for dried urine on filter paper. We studied 20 individuals from each age group ( 16 years), all without renal or metabolic disease, all on a routine food intake at the time of study. The urines were preserved with 6 mol/L HCl at pH 1–2 to prevent nonenzymatic conversion of ascorbate to oxalate. Filter paper strips (3 × 5 …

Urinary oxalate and glycolate excretion and plasma oxalate concentration.

The diagnosis of primary hyperoxaluria in young children is hampered by the lack of a reliable reference range for urinary oxalate excretion, especially in infants. We present data on urinary oxalate and glycolate excretion in 137 normal children, on the plasma oxalate concentration in 33 normal children and 53 with chronic renal failure, and on amniotic fluid oxalate concentration in 63 uncomplicated pregnancies. The urinary oxalate:creatinine molar ratios were log normally distributed: mean (range) values were less than 1 year 0.061 (0.015-0.26), 1-5 years 0.036 (0.011-0.12), 5-12 years 0.030 (0.0059-0.15), and greater than 12 years 0.013 (0.0021-0.083). Geometric mean (range) plasma oxalate concentration in the normal children was 1.53 (0.78-3.02) mumols/l and was independent of age. The mean (SD) plasma oxalate: creatinine molar ratio in these normal children and 50 with chronic renal failure was 0.033 (0.013), and was independent of age and renal function. Mean (SD) amniotic fluid oxalate concentration was 19.0 (4.3) mumols/l.

Combined liver-kidney transplantation in a child with primary hyperoxaluria

A 3.5-year-old boy presented with end-stage renal disease and bilateral nephrocalcinosis. Renal biopsy demonstrated marked parenchymal calcium oxalate deposition and a diagnosis of primary hyperoxaluria (PH) was made. Following 2 years of hemodialysis he received two renal allografts which were lost at 7 and 11 months, respectively, due to biopsy-proven recurrent oxalosis. Combined liver-kidney transplantation was then performed, after which renal and hepatic function initially stabilized. The patient died on the 28th postoperative day, of infectious complications and progressive respiratory insufficiency. However, comparisons between the patterns of urinary oxalate excretion noted after the isolated renal and liver-kidney transplants indicated that, following the latter, successful biochemical correction of the enzyme defect responsible for type 1 PH had occurred.

Livedo reticularis and peripheral gangrene associated with primary hyperoxaluria

We describe a 38-year-old man who developed livedo reticularis and peripheral gangrene after bilateral nephrectomy. Pathologic evaluation revealed extensive crystalline deposits within the walls of subcutaneous blood vessels. The diagnosis of primary hyperoxaluria was established. This case demonstrates that the vasculopathy of primary oxalosis can mimic systemic necrotizing vasculitis.

原発性過蓚酸尿症

A case of primary hyperoxaluria with calcium oxalate nephrolithiasis was presented.The patient, 24 years old male, was quite well until the age of 15 when he was diagnosed as having left renal stones with symptoms of colic pain and hematuria. At the age of 19, he was operated for pyelolithotomy under the diagnosis of right renal stones. Following this operation he passed multiple stones during 5 years. Finally he came to our clinic and was diagnosed as having left multiple renal stones and right nephrocalcinosis.The removed staghorn calculi from the left kidney by nephrolithotomy in March, 18th. 1977 was analysed as pure calcium oxalate monohydrate by infrared spectrophotomater. The histological examination of the biopsy specimen demonstrated multiple deposits of crystalline material in the renal tubules under the polarizing microscope.From these results the abnormal oxalate metabolism was suspected, so that the urinary excretion of oxalic acid was measured. His urinary excretion of oxalic acid was markedly elevated to 140mg/24hrs (167.5mg/gr creatinine), but the excretion was within normal range in his parents and relatives.According to these findings he was prescribed pyridoxal phosphate 180mg/day under the diagnosis of primary hyperoxaluria. However the treatment was not effective. At present he is on hemodialysis because of postoperative progressive renal deterioration.