Article

Renal Function in Glycogen Storage Disease Type I, Natural Course, and Renopreservative Effects of ACE Inhibition

University Medical Center Groningen, Department of Pediatrics, Hanzeplein 1, PO Box 30 001, 9700 RB Groningen, The Netherlands.
Clinical Journal of the American Society of Nephrology (Impact Factor: 4.61). 10/2009; 4(11):1741-6. DOI: 10.2215/CJN.00050109
Source: PubMed

ABSTRACT

Renal failure is a major complication in glycogen storage disease type I (GSD I). We studied the natural course of renal function in GSD I patients. We studied differences between patients in optimal and nonoptimal metabolic control and possible renoprotective effects of angiotensin converting enzyme inhibition.
Thirty-nine GSD I patients that visited our clinic were studied. GFR and effective renal plasma flow (ERPF) were measured by means of I(125) iothalamate and I(131) hippuran clearance and corrected for body surface area. Microalbuminuria was defined as >2.5 mg albumin/mmol creatinine and proteinuria as >0.2 g protein per liter. Optimal metabolic control was present when blood glucoses were >3.5 mmol/L, urine lactate/creatinine ratios <0.06 mmol/mmol, triglycerides <6.0 mmol/L, and uric acid concentrations <450 micromol/L.
Quadratic regression analysis showed a biphasic pattern in the course of GFR and ERPF related to age. Microalbuminuria was observed significantly less frequently in the patients with optimal metabolic control compared with the patients with nonoptimal metabolic control. A significant decrease in GFR was observed after starting ACE inhibition.
This study describes a biphasic pattern of the natural course of GFR and ERPF in GSD I patients, followed by the development of microalbuminuria and proteinuria. Optimal metabolic control has a renoprotective effect on the development of microalbuminuria and proteinuria in GSD I patients. Treatment with ACE inhibitors significantly decreases the GFR, especially in GSD I patients with glomerular hyperfiltration.

Full-text

Available from: Danielle Martens, Jan 08, 2016
Renal Function in Glycogen Storage Disease Type I, Natural
Course, and Renopreservative Effects of ACE Inhibition
Danie¨lle H. J. Martens,* Jan Peter Rake,
Gerjan Navis,
Vaclav Fidler,
§
Catharina M. L. van Dael,
and G. Peter A. Smit*
*Department of Pediatrics, University Medical Center Groningen, Groningen, The Netherlands;
Department of
Pediatrics, Martini Hospital Groningen, Groningen, The Netherlands;
Department of Nephrology, University Medical
Center Groningen, Groningen, The Netherlands;
§
Department of Epidemiology, University Medical Center Groningen,
Groningen, The Netherlands;
Department of Pediatric Nephrology, University Medical Center Groningen, Groningen,
The Netherlands
Background and objectives: Renal failure is a major complication in glycogen storage disease type I (GSD I). We studied the
natural course of renal function in GSD I patients. We studied differences between patients in optimal and nonoptimal
metabolic control and possible renoprotective effects of angiotensin converting enzyme inhibition.
Design, setting, participants, & measurements: Thirty-nine GSD I patients that visited our clinic were studied. GFR and
effective renal plasma flow (ERPF) were measured by means of I
125
iothalamate and I
131
hippuran clearance and corrected for
body surface area. Microalbuminuria was defined as >2.5 mg albumin/mmol creatinine and proteinuria as >0.2 g protein per
liter. Optimal metabolic control was present when blood glucoses were >3.5 mmol/L, urine lactate/creatinine ratios <0.06
mmol/mmol, triglycerides <6.0 mmol/L, and uric acid concentrations <450
mol/L.
Results: Quadratic regression analysis showed a biphasic pattern in the course of GFR and ERPF related to age. Microalbu-
minuria was observed significantly less frequently in the patients with optimal metabolic control compared with the patients
with nonoptimal metabolic control. A significant decrease in GFR was observed after starting ACE inhibition.
Conclusions: This study describes a biphasic pattern of the natural course of GFR and ERPF in GSD I patients, followed by
the development of microalbuminuria and proteinuria. Optimal metabolic control has a renoprotective effect on the devel-
opment of microalbuminuria and proteinuria in GSD I patients. Treatment with ACE inhibitors significantly decreases the
GFR, especially in GSD I patients with glomerular hyperfiltration.
Clin J Am Soc Nephrol 4: 1741–1746, 2009. doi: 10.2215/CJN.00050109
G
lycogen storage disease type I (GSD I) is an autosomal
recessive inborn error of carbohydrate metabolism
caused by a defect in the glucose-6-phosphatase
(G6Pase) enzyme complex. It has an estimated incidence of 1 in
100,000 newborns. The G6Pase enzyme complex is needed in
both glycogenolysis and gluconeogenesis to hydrolyze glucose-
6-phosphate to glucose. The enzyme defect results in severe
fasting hypoglycemia, hyperlactacidemia, hyperuricemia, and
hyperlipidemia. Untreated patients have a protruding abdo-
men because of marked hepatomegaly (storage of glycogen and
fat), short stature, truncal obesity, rounded doll face, wasted
muscles, and bleeding tendency caused by impaired platelet
function (1,2).
The disease can be well controlled metabolically by use of a
lifelong intensive dietary treatment, aimed at maintaining nor-
moglycemia and suppressing secondary metabolic derange-
ments. The diet consists of frequent meals during the day and
gastric drip feeding or uncooked cornstarch at night. The life
expectancy of patients with GSD I has considerably improved,
although various complications occur with increasing age (3).
In patients with GSD I, several renal complications have been
reported. Enlargement of the kidneys is the earliest finding,
caused by accumulation of glycogen in the kidneys and often
contributing to the diagnosis of GSD I. Because of the hyper-
uricemia, uric acid nephrolithiasis and gout nephropathy can
develop. These complications can, however, be prevented by
improvement of the metabolic derangements with dietary treat-
ment and by means of a xanthine oxidase inhibitor. Another
cause of nephrolithiasis is the decreased urinary citrate excre-
tion in combination with an increased urinary calcium excre-
tion that occurs in GSD I patients. This condition can be treated
with potassium citrate supplementation (4,5). Proximal tubular
dysfunction has also been described in patients with GSD I.
Hyperphosphaturia and loss of bicarbonate in urine can lead to
renal tubular acidosis. These findings often resolve after start-
ing intensive dietary treatment (6).
Both glomerular hyperfiltration and persistent proteinuria
have previously been reported (7–10). Renal biopsies per-
formed in three GSD I patients with persistent proteinuria
Received January 4, 2009. Accepted August 20, 2009.
Published online ahead of print. Publication date available at www.cjasn.org.
Correspondence: Dr. Danie¨lle H. J. Martens, University Medical Center Gro-
ningen, Department of Pediatrics, Hanzeplein 1, PO Box 30 001, 9700 RB Gro-
ningen, The Netherlands. Phone: 31-50-3614147; Fax: 31-50-3611704; E-mail
d.h.j.martensj@bkk.umcg.nl
Copyright © 2009 by the American Society of Nephrology ISSN: 1555-9041/411–1741
Page 1
showed focal segmental glomerulosclerosis (11). These findings
might suggest an etiology of glomerular hyperfiltration and
proteinuria similar to diabetic nephropathy (12). With increas-
ing age, the impairment of renal function in GSD I patients
might become an important factor in quality of life and life
expectancy.
In patients with diabetes, randomized controlled trials have
shown that treatment with angiotensin converting enzyme in-
hibitors (ACEi) significantly reduces the risk for onset of ne-
phropathy, the risk for progression from microalbuminuria to
microalbuminuria and increases the rate of regression to nor-
moalbuminuria (13). Even in normotensive diabetic patients,
these drugs reduce the intraglomerular pressure by specifically
relaxing the efferent glomerular arterioles (14). This effect has
not yet been proven in GSD I patients, although Melis et al. (15)
described a decrease in GFR and a delay in progression from
glomerular hyperfiltration to microalbuminuria in patients
with GSD I.
In this study, we analyzed the natural course of the GFR,
effective renal plasma flow (ERPF), and the incidence of mi-
croalbuminuria and proteinuria in 39 patients with GSD I. We
studied differences in GFR, microalbuminuria, and proteinuria
between GSD I patients classified as having optimal or nonop-
timal metabolic control. Finally, we analyzed the effects of
ACEi on the severity of microalbuminuria and proteinuria.
Materials and Methods
Patients
A total of 39 patients, 32 GSD Ia and 7 GSD Ib, that visited our clinic
were studied. The GSD I diagnosis was confirmed by enzymatic and/or
mutation analysis. Of these subjects, 16 were male and 23 were female.
Median age at diagnosis was 0.6 yr (range, 0.0 to 9.8 yr). Median age at
first investigation was 11.6 yr (range, 0.8 to 23.1 yr). Median body mass
index Z-score for age (BMI Z-score) was 0.88 (range, 3.45 to 2.92).
None of the patients had used anti-hypertensive drugs before the first
renal studies were performed. GFR measurements before and after start
of the ACEi were available in 22 patients; the median time between the
start of the ACEi and the following GFR measurement was 1.6 yr
(range, 0 to 5.1 yr).
Measurement of Laboratory and Clinical Data
GFR, ERPF, and filtration fraction (FF) measurements were per-
formed by means of I
125
iothalamate and I
131
hippuran clearance (16).
Height and weight were measured in every patient before investiga-
tion. GFR and ERPF measurements were corrected for body surface
area. Reference values for all age groups beyond 1 yr of age for GFR are
between 90 and 145 ml/min per 1.73 m
2
and for ERPF are 625 ml/min
per 1.73 m
2
(17). BP (mmHg) was determined before every GFR mea
-
surement. Hypertension was considered present when the p95 value
for age was exceeded (18). Creatinine and urea concentrations in blood
were studied before every GFR measurement.
To distinguish between patients with optimal and nonoptimal met-
abolic control, blood glucose, triglyceride, and uric acid levels, as well
as urine lactate/creatinine ratios, were studied according to standard
laboratory procedures in all patients at the time of renal investigations.
All patients were in a steady state concerning metabolic control. In
2000, the European Study on Glycogen Storage Disease type I was
completed, and biochemical targets were defined for the management
of GSD I (19). According to these guidelines, patients are considered to
have optimal metabolic control when blood glucoses are 3.5 mmol/L,
urine lactate/creatinine ratios are 0.06 mmol/mmol, triglycerides are
6.0 mmol/L, and uric acid concentrations are 450
mol/L. We
studied possible differences in the natural course of renal function
between patients with good metabolic control and patients with poor
metabolic control by assessment of the above-described biochemical
parameters.
Microalbuminuria and proteinuria were assessed in 12- and 24-h
urine collections, respectively. Microalbuminuria was defined as 2.5
mg albumin/mmol creatinine and proteinuria as 0.2 g protein/L.
Microalbuminuria assessments (mg/mmol creatinine) before and af-
ter the start of the ACEi were studied for the purpose of investigating
a possible renopreservative effect of the ACEi on renal function of GSD
I patients.
Statistical Analyses
Because the frequency of renal function measurements differed
among our patients, we analyzed the first renal function measurement
of every patient to prevent over-representation of some of the patients.
The age at first investigation varied considerably, because some of the
patients were referred to our hospital at a later age and, in some older
patients, renal function was not investigated in childhood. In total, 39
GFR, ERPF, and FF values were analyzed. GFR, ERPF, and FF mea-
surements, corrected for body surface area (BSA), were plotted against
age at the time of the investigation. The course of the GFR and ERPF in
relation to age, gender, and metabolic control was analyzed by linear
and quadratic regression (SPSS 14.0). The differences in milligram
albumin excretion per millimoles creatinine and protein excretion in
grams per liter between patients with optimal and nonoptimal meta-
bolic control were analyzed by a Mann-Whitney test (SPSS 14.0). The
incidence of microalbuminuria and proteinuria in relation to metabolic
control was analyzed by performing a Pearson
2
test (SPSS 14.0).
Differences in GFR before and after the start of the ACEi in the entire
patient group and in the subset of patients started with the ACEi in the
period of glomerular hyperfiltration were analyzed by a Wilcoxon
signed rank test (SPSS 14.0). The effects of ACEi on the severity of
microalbuminuria and proteinuria in the entire patient group and in
the subset of patients started with ACEi before the age of 12 yr was
analyzed by a Wilcoxon signed rank test (SPSS 14.0).
Results
All patients showed normal creatinine and urea concentra-
tions in blood. Hypertension was observed in 2 of 39 patients:
a 15-yr-old boy and a 23-yr-old woman. The female patient
with hypertension also had severe microalbuminuria and pro-
teinuria. According to the above-described parameters, 11 pa-
tients met the criteria for optimal metabolic control and 28
patients had nonoptimal metabolic control. The age at investiga-
tion did not differ between the patients with optimal and non-
optimal metabolic control (mean, 10.0 and 10.5 yr, respectively).
Of the 39 included patients, 26 showed glomerular hyperfil-
tration (67%). Figure 1 shows GFR corrected for BSA in relation
to age. Quadratic regression analysis showed a clear biphasic
pattern in the course of GFR related to age (P 0.01). Women
in our patient group had a significantly lower GFR than men
(P 0.02). ERPF measurements showed a similar biphasic
pattern in relation to age (P 0.00), as shown in Figure 2.
Filtration fraction ratios showed normal values for age (range,
0.19 to 0.28). Repeated GFR measurements per patient are
shown in Figure 3. The mean slope of the individual GFR
1742 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 4: 1741–1746, 2009
Page 2
curves is 0.19 ml/min per 1.73 m
2
per year between 0 and 10 yr,
0.38 ml/min per 1.73 m
2
per year between 10 and 15 yr,and
0.43 ml/min per 1.73 m
2
per year over 15 yr of age. This
confirms the biphasic pattern shown in Figure 1. The degree of
metabolic control did not have any effect on the course of the
GFR (P 0.331).
The incidence of microalbuminuria and proteinuria is shown
in Table 1. Beyond the age of 18 yr, microalbuminuria is seen in
67% and proteinuria in 42% of our patients. The patients with
nonoptimal metabolic control had a tendency toward a higher
urinary albumin excretion per millimole creatinine (median,
2.80) than the patients with optimal metabolic control (median,
1.13; P 0.09). Also, urinary protein concentrations tended to
be higher in patients with nonoptimal metabolic control (mean,
0.33 g/L) in comparison to optimal controlled patients (mean,
0.02 g/L; P 0.14). Microalbuminuria was observed signifi-
cantly less frequent in the patients with optimal metabolic
control compared with the patients with nonoptimal metabolic
control (Table 2; P 0.02). Proteinuria seemed to be less fre-
quent in the patients with optimal metabolic control compared
with patients with nonoptimal metabolic control, although no
significant difference could be found (Table 3; P 0.10).
Treatment with the ACEi started at a mean age of 14.6 yr.
Figure 4 shows the GFR values corrected for BSA, in relation to
age, before and after starting the ACEi. Regression analyses
showed no significant differences in the course of GFR, al-
though GFR in the patients without the ACEi seems to show a
higher peak GFR and a tendency toward a steeper decline
thereafter. We compared GFR values before and after starting
the ACEi in 22 GSD I patients and found a tendency toward a
decrease in GFR of 16 8 ml/min per 1.73 m
2
after starting the
ACEi (P 0.06). However, because of the biphasic course of
renal function described before, decreases in GFR can be caused
by the natural course alone. Therefore, we studied a subgroup
of 13 patients that had hyperfiltration before starting the ACEi.
In these patients, a significant decrease in GFR of 25 12
ml/min per 1.73 m
2
was observed after starting the ACEi (P
0.04).
Data on urinary albumin and protein excretion before and
after starting the ACEi were available for 23 GSD I patients. The
changes in the severity of microalbuminuria (in mg/mmol
creatinine) after the start of the ACEi varied considerably be-
tween patients. No significant decrease in microalbuminuria
after starting the ACEi could be established (P 0.80). In the
small group of patients that started with the ACEi before the
age of 12 yr (n 8), no differences in the degree of microalbu-
minuria after starting the ACEi could be found (P 0.21). No
decrease in proteinuria was observed after starting the ACEi
(P 0.67). Also, in the patients that started the ACEi before the
age of 12 yr, no decrease in proteinuria could be seen (P 0.65).
Discussion
Our data suggest that the natural course of renal function in
GSD I shows a biphasic pattern with a peak GFR in the mid-
second decade. The course of the ERPF shows a similar course,
indicating that hyperperfusion is the cause of the hyperfiltra-
tion in GSD I patients as opposed to an increased intraglomeru-
lar pressure, in which a normal ERPF and an increased FF
would be expected.
Even in some of our youngest patients, microalbuminuria
and proteinuria was detected. In the young adult GSD I pa-
tients (18 to 24 yr), microalbuminuria was present in 67% and
proteinuria in 42% of patients.
This pattern of hyperfiltration, later accompanied by mi-
croalbuminuria and overt proteinuria, followed by a decline in
GFR thereafter, resembles the course of diabetic nephropathy
(12). This resemblance is confirmed by the fact that histologic
studies of renal biopsies in GSD I patients have shown similar-
ities with the histologic findings in diabetic nephropa-
thy(20,21). In diabetic patients, however, hypertension is an
important additional risk factor in the development of ne-
phropathy (14). In our group of GSD I patients, hypertension
did not seem to play a role in the development of nephropathy,
because only two of our patients met the criteria for hyperten-
Figure 1. Natural course of GFR in GSD I patients.
Figure 2. Natural course of ERPF in GSD I patients.
Clin J Am Soc Nephrol 4: 1741–1746, 2009 Natural Course of Renal Function in GSD I and Effects of ACEi 1743
Page 3
sion. Moreover, even in GSD I patients with apparent dyslipi-
demia, no premature atherosclerosis was shown (22).
The degree of metabolic control did not influence the course
of the GFR in our patients, but the patients with nonoptimal
metabolic control showed a tendency toward higher urinary
albumin excretions in comparison to the patients in optimal
metabolic control. Moreover, a higher incidence of microalbu-
minuria and a trend toward a higher incidence of proteinuria
was seen in the group with nonoptimal metabolic control com-
pared with the patients with optimal metabolic control. Al-
though the assessment of metabolic control took place at the
time of the first renal investigation, it has shown to be a good
reflection of the metabolic control of a longer period of time in
our patients. Our data therefore indicate that optimal metabolic
control has a renoprotective effect on the development of mi-
Figure 3. Repeated GFR measurements per patient.
Table 1. Incidence of microalbuminuria and proteinuria per age group
0–6 yr 6–12 yr 12–18 yr 18–25 yr
Microalbuminuria 5/9 (55%) 2/8 (25%) 0/7 (0%) 8/12 (67%)
Proteinuria 0/9 (0%) 1/8 (13%) 0/7 (0%) 5/12 (42%)
Table 2. Relationship between microalbuminuria and
metabolic control
Metabolic Control
Total
Nonoptimal Optimal
Microalbuminuria
Present 14 1 15
Not present 12 9 21
Total 26 10 36
Table 3. Relationship between proteinuria and
metabolic control
Metabolic Control
Total
Nonoptimal Optimal
Proteinuria
Present 6 0 6
Not present 20 10 30
Total 26 10 36
Figure 4. GFR in GSD I patients before and after ACE inhibition.
1744 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 4: 1741–1746, 2009
Page 4
croalbuminuria and a possible renoprotective effect on the de-
velopment of proteinuria in GSD I patients.
In patients with diabetic nephropathy, a renoprotective effect
of the ACEi has been described (13,14). In our patients, a
significant decrease in GFR was observed when the ACEi was
prescribed to the patients with glomerular hyperfiltration. We
could not prove a renoprotective effect of the ACEi on the
severity of microalbuminuria and proteinuria in our study
group of GSD I patients. This could be because of the relative
small number of patients and the fact that, in a large group of
these patients, an ACEi was not started until glomerular hy-
perfiltration or microalbuminuria had been established. How-
ever, in diabetic nephropathy, treatment with the ACEi in the
presence of microalbuminuria and even the ACEi treatment of
overt diabetic nephropathy have been shown to be effective
(14). Probably, renal damage in GSD I patients is caused early
in life by increased amounts of glucose-6-phosphate, leading to
activation of the protein kinase C and upregulation of the renal
angiotensinogen (12). This might explain why starting an ACEi
later in life does not have an influence on the development of
microalbuminuria and proteinuria. In that case, ACEi treatment
should be started earlier, as suggested by Melis et al. (15), in the
stage of hyperfiltration, to prevent renal damage. In diabetic
patients, hypertension is an important risk factor in the devel-
opment of diabetic nephropathy. The majority of our patients
did not have hypertension, and therefore, an ACEi might not
have such a significant effect as is seen in diabetic patients.
However, in the earlier stages of renal disease, diabetic patients
with microalbuminuria often are normotensive (14), so hyper-
tension might become apparent later in life in GSD I patients.
Long-term follow-up of GSD I patients is necessary to see if
hypertension will develop in these patients. Prospective stud-
ies, started early in life, are needed to investigate whether an
ACEi might be of benefit in GSD I patients.
In conclusion, this study described a biphasic pattern of the
natural course of GFR and ERPF in GSD I patients, followed by
the development of microalbuminuria and proteinuria. This
bears resemblance to the development of nephropathy in pa-
tients with diabetes mellitus, although GSD I patients lack the
risk factors of hypertension and arteriosclerosis, as is seen in
diabetic patients. Optimal metabolic control has a renoprotec-
tive effect on the development of microalbuminuria and pro-
teinuria in GSD I patients. Treatment with an ACEi signifi-
cantly decreases the GFR, especially in GSD I patients with
glomerular hyperfiltration. The ACEi did not decrease the se-
verity of microalbuminuria or proteinuria in this group of
patients. However, this effect might become more clear in a
larger number of patients started with an ACEi early in life.
Therefore, prospective trials, studying this possible renoprotec-
tive effect of ACEi, are warranted.
Acknowledgments
Part of this work was published as an abstract of an oral presentation
held at the 37th Annual Meeting of the American Society of Nephrol-
ogy, St. Louis, MO; October 29 through November 1, 2004.
Disclosures
None.
References
1. Scriver C, Childs B: The Metabolic and Molecular Bases of
Inherited Disease, 8th Ed., New York, McGraw-Hill, Medical
Publishing Division, 2005
2. Fernandes J, Saudubray JM, Berghe GVD: Inborn Metabolic
Diseases: Diagnosis and Treatment, 4th Ed., Berlin, Springer,
2006
3. Rake JP, Visser G, Labrune P, Leonard JV, Ullrich K, Smit
GP: Glycogen storage disease type I: Diagnosis, manage-
ment, clinical course and outcome. Results of the European
Study on Glycogen Storage Disease Type I (ESGSD I). Eur
J Pediatr 161[Suppl 1]: S20–S34, 2002
4. Restaino I, Kaplan BS, Stanley C, Baker L: Nephrolithiasis,
hypocitraturia, and a distal renal tubular acidification de-
fect in type 1 glycogen storage disease. J Pediatr 122: 392–
396, 1993
5. Weinstein DA, Somers MJ, Wolfsdorf JI: Decreased urinary
citrate excretion in type 1a glycogen storage disease. J Pe-
diatr 138: 378–382, 2001
6. Reitsma-Bierens WC: Renal complications in glycogen
storage disease type I. Eur J Pediatr 152[Suppl 1]: S60–S62,
1993
7. Lee PJ, Dalton RN, Shah V, Hindmarsh PC, Leonard JV:
Glomerular and tubular function in glycogen storage dis-
ease. Pediatr Nephrol 9: 705–710, 1995
8. Lee PJ, Leonard JV: The hepatic glycogen storage diseases:
Problems beyond childhood. J Inherit Metab Dis 18: 462–
472, 1995
9. Chen YT: Type I glycogen storage disease: Kidney involve-
ment, pathogenesis and its treatment. Pediatr Nephrol 5:
71–76, 1991
10. Baker L, Dahlem S, Goldfarb S, Kern EF, Stanley CA, Egler
J, Olshan JS, Heyman S: Hyperfiltration and renal disease
in glycogen storage disease, type I. Kidney Int 35: 1345–
1350, 1989
11. Chen YT, Coleman RA, Scheinman JI, Kolbeck PC, Sidbury
JB: Renal disease in type I glycogen storage disease. N Engl
J Med 318: 7–11, 1988
12. Mundy HR, Lee PJ: Glycogenosis type I and diabetes mel-
litus: A common mechanism for renal dysfunction? Med
Hypotheses 59: 110–114, 2002
13. Strippoli GF, Craig MC, Schena FP, Craig JC: Role of blood
pressure targets and specific antihypertensive agents used
to prevent diabetic nephropathy and delay its progression.
J Am Soc Nephrol 17: S153–S155, 2006
14. Ibrahim HA, Vora JP: Diabetic nephropathy. Baillieres Best
Pract Res Clin Endocrinol Metab 13: 239–264, 1999
15. Melis D, Parenti G, Gatti R, Casa RD, Parini R, Riva E,
Burlina AB, Vici CD, Di RM, Furlan F, Torcoletti M, Papa-
dia F, Donati A, Benigno V, Andria G: Efficacy of ACE-
inhibitor therapy on renal disease in glycogen storage dis-
ease type 1: A multicentre retrospective study. Clin
Endocrinol (Oxf) 63: 19–25, 2005
16. Apperloo AJ, de Zeeuw D, Donker AJ, de Jong PE: Preci-
sion of glomerular filtration rate determinations for long-
term slope calculations is improved by simultaneous infu-
sion of 125I-iothalamate and 131I-hippuran. JAmSoc
Nephrol 7: 567–572, 1996
Clin J Am Soc Nephrol 4: 1741–1746, 2009 Natural Course of Renal Function in GSD I and Effects of ACEi 1745
Page 5
17. Piepsz A, Tondeur M, Ham H: Revisiting normal (51)Cr-
ethylenediaminetetraacetic acid clearance values in chil-
dren. Eur J Nucl Med Mol Imaging 33: 1477–1482, 2006
18. Update on the 1987 Task Force Report on High Blood
Pressure in Children and Adolescents: A working group
report from the National High Blood Pressure Education
Program. National High Blood Pressure Education Pro-
gram Working Group on Hypertension Control in Chil-
dren and Adolescents. Pediatrics 98:649 658, 1996
19. Rake JP, Visser G, Labrune P, Leonard JV, Ullrich K, Smit GP:
Guidelines for management of glycogen storage disease type
I-European Study on Glycogen Storage Disease Type I
(ESGSD I). Eur J Pediatr 161[Suppl 1]: S112–S119, 2002
20. Obara K, Saito T, Sato H, Ogawa M, Igarashi Y, Yoshinaga
K: Renal histology in two adult patients with type I glyco-
gen storage disease. Clin Nephrol 39: 59 64, 1993
21. Verani R, Bernstein J: Renal glomerular and tubular abnor-
malities in glycogen storage disease type I. Arch Pathol Lab
Med 112: 271–274, 1988
22. Ubels FL, Rake JP, Slaets JP, Smit GP, Smit AJ: Is glycogen
storage disease 1a associated with atherosclerosis? Eur J Pe-
diatr 161[Suppl 1]: S62–S64, 2002
1746 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 4: 1741–1746, 2009
Page 6
  • Source
    • "Allopurinol and angiotensinconverting enzyme (ACE) inhibitors are used as supplementary drug to lower the uric acid and microalbuminuria [20]. Adjunct therapy during G6Pase deficiency includes lipid lowering drugs and potassium citrate [26, 33, 34]. Liver transplantation in the patient with GSD-1a can be performed if dietary therapy becomes unresponsive to hepatocellular adenoma and tumors. "
    [Show abstract] [Hide abstract] ABSTRACT: One of the extreme challenges in biology is to ameliorate the understanding of the mechanisms which emphasize metabolic enzyme deficiency (MED) and how these pretend to have influence on human health. However, it has been manifested that MED could be either inherited as inborn error of metabolism (IEM) or acquired, which carries a high risk of interrupted biochemical reactions. Enzyme deficiency results in accumulation of toxic compounds that may disrupt normal organ functions and cause failure in producing crucial biological compounds and other intermediates. The MED related disorders cover widespread clinical presentations and can involve almost any organ system. To sum up the causal factors of almost all the MED-associated disorders, we decided to embark on a less traveled but nonetheless relevant direction, by focusing our attention on associated gene family products, regulation of their expression, genetic mutation, and mutation types. In addition, the review also outlines the clinical presentations as well as diagnostic and therapeutic approaches.
    Full-text · Article · Mar 2016
  • Source
    • "In GSDIa patients, renal failure was the most common complication (14/58 (24%) of patients) and 3/14 (21%) required dialysis. The natural course of renal function in GSDI patients shows a biphasic pattern [41]. We identified only 1 patient with both pre- and post-transplantation renal failure; renal function was restored in the other 4 patients with pre-transplantation renal dysfunction. "
    [Show abstract] [Hide abstract] ABSTRACT: Glycogen storage disease type I (GSDI), an inborn error of carbohydrate metabolism, is caused by defects in the glucose-6-transporter/glucose-6-phosphatase complex, which is essential in glucose homeostasis. Two types exist, GSDIa and GSDIb, each caused by different defects in the complex. GSDIa is characterized by fasting intolerance and subsequent metabolic derangements. In addition to these clinical manifestations, patients with GSDIb suffer from neutropenia with neutrophil dysfunction and inflammatory bowel disease. With the feasibility of novel cell-based therapies, including hepatocyte transplantations and liver stem cell transplantations, it is essential to consider long term outcomes of liver replacement therapy. We reviewed all GSDI patients with liver transplantation identified in literature and through personal communication with treating physicians. Our review shows that all 80 GSDI patients showed improved metabolic control and normal fasting tolerance after liver transplantation. Although some complications might be caused by disease progression, most complications seemed related to the liver transplantation procedure and subsequent immune suppression. These results highlight the potential of other therapeutic strategies, like cell-based therapies for liver replacement, which are expected to normalize liver function with a lower risk of complications of the procedure and immune suppression.
    Full-text · Article · Apr 2014 · Orphanet Journal of Rare Diseases
  • Source
    • "Similarly, optimal metabolic control has been reported to have a protective effect on the development of microalbuminuria and proteinuria in patients with GSD I [12]. Normal bone density has also been associated with improved metabolic control in patients with GSD Ia [13]. "
    [Show abstract] [Hide abstract] ABSTRACT: Glycogen storage disease type IX (GSD IX) is described as a benign condition that often does not require treatment. Most patients with the disease are thought to outgrow the childhood manifestations, which include hepatomegaly, poor growth, and ketosis with or without hypoglycemia. Long term complications including fibrosis and cirrhosis have seldom been reported in the most common subtype, GSD IXα. We present two cases of children with GSD IXα who had fibrosis at the time of diagnosis in addition to the commonly reported disease manifestations. Structured therapy with frequent doses of uncooked cornstarch and protein supplementation was initiated, and both children responded with improved growth velocity, increased energy, decreased hepatomegaly and improved well-being. Additionally, radiographic features of fibrosis improved. We propose that GSD IXα is not a benign condition. Even in patients with a less severe presentation, consideration of a structured treatment regimen to improve quality of life appears warranted.
    Full-text · Article · Mar 2013 · Molecular Genetics and Metabolism
Show more