Renal function and kidney size in glycogen storage disease type I

Renal failure has been reported recently as a late complication of glycogen storage disease type I (GSD I). We studied the renal function of 23 patients, mean age 10.9 years (range 2.2–21.6 years). The mean glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were 188±50 and 927±292 ml/min per 1.73 m², respectively (normal values for adult controls 90–145 and 327–697, respectively). Hyperfiltration (GFR >145 ml/min per 1.73 m²) was found in 19 of 23 patients. There was no difference in GFR and ERPF between age groups 2–10 and 11–22 years. After a mean follow-up of 2.5 years (range 1–7.5 years) GFR and ERPF did not significantly change. At follow-up 3 patients (all older than 15 years) developed persistent glomerular proteinuria (0.1, 0.5 and 0.9 g/day). Besides a slight increase in fractional excretion of ₂-microglobulin (FE-₂m) in 6 patients, proximal tubular function tests (FE-₂m, tubular reabsorption of phosphate and glucosuria) were normal. In patients with increased kidney length related to body height, GFR and ERPF were significantly higher than in patients with normal kidney length. We conclude that GSD I is characterised by hyperfiltration and hyperperfusion. The relative increment in kidney length is related to the degree of hyperfiltration.     

肝糖原贮积症肾脏并发症的临床观察

目的 观察儿童期肝糖原贮积症（GSD）的肾脏并发症.方法 回顾性分析1993年1月-2004年1月北京协和医院108例病历完整的GSD患儿的肾脏损害的临床特点、治疗和预后.年龄≤10岁73例,10岁以上35例.病例随诊时间1～10年,随诊期间给予生玉米淀粉为主的综合治疗.结果 临床诊断GSD-Ⅰ a型54例（23例进行了基因诊断）;Ⅲ型29例（5例进行了基因诊断）;分型不明的25例.16例（20.8%）尿蛋白增多,发现蛋白尿时平均年龄11.3（3～21）岁,2例15岁女孩24h尿蛋白定量已达1.3 g和3.8 g,同时伴有肾功能轻度受损.51/72例（70.8%）尿β2-MG增多,为175～10 623 mg/L.5例患儿（4.6%）出现肾结石或高尿钙症,发生时年龄17.8（11～21）岁;4/5例肾绞痛伴肉眼血尿,1/5例无症状;随诊发现镜下血尿及大量草酸钙结晶,24 h尿钙456.6 mg,B型超声证实双肾多发结石.10/17例Ccr降低（48～76.9 ml/min）;2/17例Ccr升高（156.9～1819 ml/min）.5/91例BUN升高（7.4～9.3 mol/L）;1/91例Scr升高（106.1 μmol/L）.结论 GSD的肾脏合并症在儿童期已可以见到,主要表现为尿蛋白增多（白蛋白及肾小管蛋白）和肾石症,直至肾功能不全,症状随年龄增大而逐渐出现.应加强GSD患儿肾脏并发症的随诊.     

Urolithiasis and psoas abscess in a 2-year-old boy with type 1 glycogen storage disease

We report on a pyogenic psoas abscess secondary to an impacted calcium oxalate ureteric stone in a 2-year-old boy with glycogen storage disease type 1 (GSD-1). The patient had a drainage of the abscess through a flank incision followed by percutaneous nephrostomy and open ureterolithotomy. Metabolic acidosis, hyperuricemia, hypocitraturia, and hypercalciuria appear to be significant in the pathogenesis of urolithiasis in patients with GSD-1. Regular ultrasonography of the abdomen along with optimal metabolic control may delay or prevent urolithiasis and its complications in GSD-1 patients.     

Perioperative management of benign hepatic tumors in patients with glycogen storage disease type Ia

Glycogen storage disease type Ia (GSD-Ia; von Gierke disease) is an inherited disorder caused by glucose-6-phosphatase deficiency, and there have been some reports of hepatic tumors in patients with this disease. We report two patients with benign hepatic tumors with GSD-Ia. One is a 19-year-old man who underwent segmentectomy 4 for a focal nodular hyperplasia, and the other is a 31-year-old woman who underwent segmentectomies 3, 5, and 6 for hepatic adenomas. Two significant perioperative complications, resulting from the carbohydrate metabolic disorders, hypoglycemia and metabolic acidosis, occurred in both patients. We managed the metabolic complications successfully by administering a sufficient volume of glucose intravenously. Close perioperative monitoring of blood glucose and lactate concentrations is essential in the perioperative management of patients with GSD-Ia. The intravenous administration of glucose, starting with a smaller dose and then increasing the dose, is adequate management for lactic acidosis with or without hypoglycemia during the perioperative period.     

Calcium nephrolithiasis and distal tubular acidosis in type 1 glycogen storage disease

A 36-year-old man was admitted to hospital due to right flank pain as a result of ureteral stones. He had been followed up for type 1 glycogen storage disease since the age of 11 years. He had four episodes of spontaneous stone birth during the previous 2 years, and each stone was composed mainly of calcium oxalate. Intravenous pyelography showed right hydronephrosis due to ureteral stones and bilateral multiple renal stones. We carried out transurethral ureterolithotripsy (TUL) on the right ureteral stones. The composition was a mixture of calcium oxalate and calcium phosphate. Laboratory evaluation demonstrated the association of distal renal tubular acidosis (RTA). These observations suggest that hypocitraturia and distal RTA are strongly correlated to recurrence of calcium nephrolithiasis. The patient's serum uric acid and urinary citrate excretion levels normalized after allopurinol and potassium citrate administration.     

Type I glycogen storage disease: Kidney involvement,pathogenesis and its treatment

Type I glycogen storage disease (GSD-I) is due to the deficiency of glucose-6-phosphatase activity in the liver, kidney and intestine. Although kidney enlargement occurs in GSD-I, renal disease has not been considered a major problem until recently. In older patients (more than 20 years of age) whose GSD-I disease has been ineffectively treated, virtually all have disturbed renal function, manifested by persistent proteinuria; many also have hypertension, renal stones, altered creatinine clearance or a progressive renal insufficiency. Glomerular hyperfiltration is seen in the early stage of the renal dysfunction and can occur before proteinuria. In younger GSD-I patients, the hyperfiltration is usually the only renal abnormality found; and, in some patients, microalbuminuria develops before clinical proteinuria. The predominant underlying renal pathology is focal segmental glomerulosclerosis. Renal stones and/or nephrocalcinosis are also common findings. Amyloidosis and Fanconi-like syndrome can occur, but rarely. The risk factors for developing the glomerulosclerosis in GSD-I include hyperfiltration, hypertension, hyperlipidemia and hyperuricemia. Dietary therapy with cornstarch and/or nasogastric infusion of glucose, aimed at maintaining normoglycemia, corrects metabolic abnormalities and improves the proximal renal tubular function. Long-term trial will be needed to assess whether the dietary therapy may prevent the evolution or the progression of the renal disease.     

Acute pancreatitis after anesthesia with propofol in a child with glycogen storage disease type IA

Glycogen storage disorder type 1A (GSD 1A) is an inherited disorder of glycogen metabolism characterized by fasting hypoglycemia, lactic acidosis, hyperuricemia, and hyperlipidemia. These children have a higher risk of developing pancreatitis because of hypertriglyceridemia. Drug-induced pancreatitis accounts for a small proportion of cases of pancreatitis. The mechanism of drug-induced pancreatitis include hypersensitivity, direct toxic injury or indirectly by inducing hypertriglyceridemia. Propofol is often the drug of choice for induction of anesthesia in ambulatory surgical procedures. There are various reports in the literature describing pancreatitis induced by propofol. We present a 4-year-old girl with GSD 1A, who required tonsillectomy and adenoidectomy under general anesthesia. She developed acute pancreatitis in the postoperative period. Propofol was used as a general anesthetic and the postoperative incidence of pancreatitis is discussed.     

Elevated tubular proteinuria, albuminuria and decreased urinary N-acetyl-β-D-glucosaminidase activity following unilateral total ureteral obstruction in rats

Urinary tubular proteinuria and N-acetyl-β-d-glucosaminidase (NAG) activity has not yet been studied after unilateral total ureteral obstruction (UTO). The aim of the study was (1) to evaluate in a longitudinal study (7 weeks) the behaviour and the potential clinical value of tubular proteinuria and urinary NAG activity after UTO; (2) to study the physiopathology of the non-obstructed contralateral kidney by using these two different markers of tubular damage. Methods: in 28 female, adult Wistar rats (UTO: n= 16, sham: n= 12), tubular proteinuria and urinary NAG activity were measured before and 1 and 5 weeks after surgery. Results: a significant (P < 0.01) increase in tubular proteinuria/creatinine ratio and urinary creatinine and a decrease in urinary NAG activity was found 1 week after UTO. All parameters normalized after 6 weeks. Albuminuria increased progressively (P < 0.01) during the study. Conclusion: tubular proteinuria increases during the first week following UTO in rats. The initial increase of low molecular weight proteins following UTO is not due to tubular damage as no parallel increase of urinary NAG was found. We suggest an initial tubular overperfusion with primary urine, due to an increased single nephron glomerular filtration and overruling the reabsorption capacity of the proximal tubules. Received: 1 December 1997 / Accepted: 2 March 1998     

Glomerular morphometry in reflux nephropathy: functional and radiological correlations

Using computerized digitometry, we investigated the relationships between renal size, glomerular filtration rate (GFR), proteinuria, incidence of segmental and global glomerulosclerosis, glomerular size, hilar arteriolar wall thickness and hyaline deposition in renal biopsies obtained from 24 children and adolescents with reflux nephropathy, of whom only 4 were hypertensive. Agematched controls comprised minimal-change nephrotic syndrome (6) and recurrent haematuria with normal biopsy (13). The mean sectional area of patients' glomeruli was double that of controls. Glomerular size correlated with the amount of proteinuria (measured as protein/creatinine ratios in early morning urine) and inversely with renal size and GFR. Segmental sclerosis, invariably of hilar origin, was observed in 8 patients and the percentage of glomeruli affected correlated strongly with glomerular size and proteinuria. Global sclerosis was found equally in patients and controls, and showed no similar correlations. Compared with controls, patients' hilar arterioles showed increased wall thickness, more intramural hyaline deposits and decreased luminal diameter when related to glomerular size. The proteinuria and glomerular changes are consistent with hyperfiltration, while the previously undescribed hilar vascular changes, which both precede and accompany sclerosis, resemble abnormalities reported experimentally following renal ablation.     

Role of prostaglandins in hyperprostaglandin E syndrome and in selected renal tubular disorders

Renal and systemic prostanoid activity was assessed in various renal tubular disorders, using mass spectrometric determination of urinary excretion rates of primary prostaglandins (PGE₂, PGF₂, PGI₂, and TXA₂) and their systemically produced index metabolites. Only PGE₂ levels (normal range: 2.0–16.4 ng/h per 1.73 m²) are elevated in Bartter syndrome (median: 43.4, range: 6.7–166.3), nephrogenic diabetes insipidus (46.2, 12.1–1290), Fanconi syndrome (96.6, 19.3–135.5), and in a complex tubular disorder in premature infants (40.7, 22.3–132.1), for which the term hyperprostaglandin E syndrome has been introduced. In this disorder with a Bartter-syndrome-like tubulopathy, the systemic features of the disease such as fever, diarrhoea and osteopenia with hypercalciuria were associated with increased systemic PGE₂ activity. In most patients the urinary excretion rate of the systemic index metabolite of PGE₂ (PGE-M) was markedly elevated (1028, 285–4709; normal range: 104–664 ng/h per 1.73 m²). Hypercalciuria per se was associated neither with increased renal nor with systemic PGE₂ hyperactivity. Most problems in infants with hyperprostaglandin E syndrome could be controlled by long-term indomethacin treatment in contrast to the moderate and partial effect of this treatment in patients with Fanconi syndrome. Thus increased PGE₂ synthesis plays a major role in the pathogenesis of hyperprostaglandin E syndrome, while in Fanconi syndrome PGE₂ hyperactivity in the kidney is a secondary event and only aggravates the water and electrolyte wastage.Supported by the Deutsche Forschungsgemeinschaft (Se 263/9-1). H. W. Seyberth is in receipt of a Heisenberg Stipend from the Deutsche Forschungsgemeinschaft     

Outcomes of liver transplantation for glycogen storage disease: a matched-control study and a review of literature

Maheshwari A, Rankin R, Segev DL, Thuluvath PJ. Outcomes of liver transplantation for glycogen storage disease: a matched‐control study and a review of literature.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01549.x.
© 2011 John Wiley & Sons A/S. Abstract: Background: The clinical characteristics and outcomes of patients with glycogen storage disease (GSD) who undergo liver transplantation (LT) have not been well defined. In this study, our objective was to determine the outcome of LT in patients with GSD and compare it with a comparable group of patients without GSD (matched controls). Methods: UNOS data from 1986 to 2007 were used for this study. For each GSD patient (n = 95; men 62%) who was transplanted, three patients (n = 285, men 60%) without GSD (case controls) matched for age ± five yr, year of transplantation and donor risk index (DRI) ± 0.2 were identified from the UNOS database in a random manner. Unadjusted patient survival was determined by Kaplan–Meier survival analysis and significance determined by log‐rank test. Results: The mean age of the group was 17.9 yr. GSD patients had lower BMI (22 vs. 24, p = 0.002), lower serum bilirubin (2.7 vs. 13.5 mg/dL, p < 0.0001), higher serum albumin (3.7 vs. 3.1 g/dL, p < 0.0001), and higher wait‐list time (239 vs. 74 d, p < 0.0001) compared to case controls. Recipient age and DRI were similar between the groups. Tumors were more common in GSD group (13.7% vs. 5%). Patient survival was significantly better (p = 0.024) in GSD group at one, five, and 10 yr (82%, 76%, and 64%) than non‐GSD (73%, 65%, and 59%) group. Conclusions: In this matched‐control study, patients who underwent LT for GSD had a better long‐term survival than a comparable group of patients without GSD.     

Urinary excretion of tubular proteins and the technetium-99m dimercaptosuccinic acid (DMSA) absolute renal uptake in partial ureteral obstruction in rats: a functional evaluation of hydronephrotic kidneys

The aim of this longitudinal study was to evaluate tubular proteinuria in rats with unilateral (UPO) and bilateral (BPO) partial ureteral obstruction with the dimercaptosuccinic acid (DMSA) scan as the gold standard for measuring renal tubular damage. We studied 70 female Wistar rats: 28 animals with UPO, 28 animals with BPO, 7 sham-operated animals, and 7 controls. All animals with obstructed ureters showed renal dilatation on the diethylenetriaminepentaacetic acid DTPA images 1 and 5 weeks postoperatively. One week following UPO and BPO, tubular proteinuria and urinary N-acetyl-beta-d-glucosaminidase (NAG) activity increased (P < 0.01) and the absolute DMSA uptake decreased (P < 0.01). Persistently (week 6) high tubular proteinuria was found in 29% of the animals and was related to severe damage on the DMSA scan (P < 0.01) and to albuminuria (P < 0.05). Renal tubular damage was demonstrated by measuring renal enzymes, tubular proteins, and DMSA uptake after UPO and BPO. Persistent elevated tubular proteinuria was related to severely damaged kidneys. Received: 18 June 1998 / Accepted: 20 October 1998     

Defective proximal tubular function in a patient with I-cell disease

A girl with a proven diagnosis of I-cell disease is presented. Proximal tubular dysfunction was characterized by increased excretion of low molecular proteins, aminoaciduria, hyperphosphaturia, and high/slightly increased urinary calcium. The concentration of 1,25-dihydroxycalciferol in serum was increased. Rickets were present on X-rays. As the proximal tubular dysfunction resembles the dysfunction in Dent disease, one can speculate about a common pathogenesis. Impairment of acidification in lysosomes due to loss of function of the chloride-5 channel impairs intralysosomal protease activity in Dent disease, while in I-cell disease the intralysomal protease activity is lacking.     

Proteinuria and other renal functions in Wilson’s disease

Renal lesions have repeatedly been described in Wilson’s disease (WD). We investigated the excretion of total protein, albumin, low (LMW) and high molecular weight (HMW) proteins, N-acetyl-β-D-glucosaminidase (NAG), and calcium, as well as creatinine clearance, in 24-h urine samples of 41 patients with WD aged 6 – 37 (mean 17) years who had been treated for a period of 0 – 15 (mean 4.5) years with D-penicillamine (900 mg/day). The amount of all protein excreted was significantly increased compared with controls, 39% of patients presenting with total proteinuria more than two standard deviations from the mean of controls. The changes in protein excretion depended on the duration of treatment. LMW proteinuria was elevated almost exclusively in the first 2 years after the start of treatment, indicating early tubular damage. This is supported by an initially high excretion of β₂-microglobulin, NAG, and calcium. Increased excretion of HMW proteins, including albumin, persisted over longer periods, which suggests glomerular injury in some patients, possibly related to the use of D-penicillamine. Creatinine clearance remained roughly within normal limits. We propose that renal function should regularly be checked in patients with WD. Received October 26, 1995; received in revised form August 27, 1996; accepted September 20, 1996     

Medullary cystic disease and tubular basement membrane changes: clinicopathological characteristics of four patients

We describe herein the clinicopathological characteristics of four members of a family in which about half of the generation was affected by chronic renal failure after middle age. The inheritance was considered to be an autosomal dominant pattern. Clinically, neither sensorineural deafness nor ocular abnormalities were evident. In addition, there was neither hypokalemia nor hypercalcemia causing deterioration of renal function. Radiological examination revealed no cystic formation in the kidneys in any patients, although in two of them the examination was performed at the time of endstage renal disease. Histological examination showed chronic tubulo-interstitial damage with periglomerular fibrosis. On electron microscopy, characteristic but nonspecific thickening and lamination of tubular basement membrane were noted in all patients, while glomerular basement membrane was unremarkable in all patients. These findings suggest that our patients had medullary cystic disease. Demonstration of lamination and thickening of the tubular basement membrane by electron microscopy may be useful for the diagnosis of medullary cystic disease with undetectable cyst formation. Received: December 1, 1999 / Accepted: October 16, 2000     

Examination of megalin in renal tubular epithelium from patients with Dent disease

Dent disease is characteristic for the urinary loss of low-molecular-weight proteins and calcium, leading to renal calcification and, in some patients, chronic renal failure. This disorder is caused by loss-of-function mutations in the renal chloride channel gene, CLCN5. The animal model of this disease has demonstrated the possible role of disturbed megalin expression, which is a member of the low-density lipoprotein receptor family and is associated with renal reabsorption of a variety of proteins, in Dent disease. We examined the expression of megalin in the renal tubular epithelium of two unrelated patients with Dent disease. One patient, whose CLCN5 gene was completely deleted, showed significantly decreased staining of megalin compared with controls, while there was no change in another patient with partial deletion of the gene. These results demonstrated that mutation of CLCN5 in some patients with Dent disease may impair the expression of megalin, resulting in abnormal calcium metabolism, manifested as hypercalciuria and nephrocalcinosis.