Symposium on Pediatric Nephrology

Treatment of Steroid Sensitive Nephrotic Syndrome

A.S. Abeyagunawardena

Department of Pediatrics, Faculty of Medicine, University of Peradeniya, Sri Lanka

Abstract. Childhood idiopathic nephrotic syndrome (NS) is a chronic glomerular disorder, and if untreated, is associated with
increased risk of life-threatening infections, thromboembolism, lipid abnormalities, and malnutrition. The aim of the management
of NS in children is to induce and maintain complete remission with resolution of proteinuria and edema without encountering
serious adverse effects of therapy. Over 90% of cases in children are due to minimal change disease (MCD) and a majority
of them will respond to corticosteroid therapy. Steroid sensitive NS is considered to be a relatively benign condition; progression
to end stage renal failure is extremely rare and over 80% achieve spontaneous remission in later childhood. The early disease
is characterized by a relapsing course, placing the child at risk of acute complications. The occurrence of frequent relapses
necessitates clear therapeutic strategies in order to maintain sustained remission and minimize steroid toxicity. Numerous
therapeutic regimens have been proposed utilizing steroid sparing agents such as alkylating agents, principally,
cyclophosphamide and chlorambucil, calcineurin inhibitors namely cyclosporin A and immunomodulatory drug levamisole with
variable success and associated side-effects. It is therefore important that the benefits and risks of these agents are weighed
before considering their use in the treatment of patients with NS. [Indian J Pediatr 2005; 72 (9) : 763-769]
E mail : asiri26@hotmail.com

Key words : Idiopathic nephrotic syndrome; Corticosteroid therapy; Minimal change disease

Idiopathic nephrotic syndrome (NS) is a common
glomerular disorder in childhood characterized by heavy
proteinuria, hypoproteinemia, edema and
hyperlipidemia. Estimates of annual incidence range from
2 to 7 new cases in children under 16 yrs per 100,000 total
populations, leading to a cumulative prevalence of 15.7
per 100,000 due to the chronic nature of the disease. There
is however a racial variation in the susceptibility with a
reported incidence of 9-16 per 100,000 in British Asian
children.1
Most patients with NS have minimal changes in the
glomeruli on histology and 90%-95% will respond to
corticosteroid therapy. 2 There is a close correlation
between steroid sensitivity and minimal change disease
(MCD), and therefore at the initial presentation, a renal
biopsy is not performed in the absence of risk factors
suggesting other forms of NS. A minority of children with
underlying focal segmental glomerulosclerosis (FSGS)
and diffuse mesangial proliferative glomerulonephritis
will also respond to corticosteroid therapy. Consequently,
a clinically useful classification of NS is that of steroid
sensitive NS (SSNS), or steroid resistant NS (SRNS). SSNS
has a more favorable outcome with a high probability of
long-term remission and preserved renal function, while
the prognosis of SRNS is more guarded, with a significant
proportion progressing to end stage renal failure.
A perturbation of the immune system was proposed
Correspondence and Reprint requests : Dr. Abeyagunawardena
A.S., Department of Pediatrics, Faculty of Medicine, University of
Peradeniya, Sri Lanka. Phone : 0812222069
by Shalhoub3 to be important in the pathogenesis of NS. It
was also known that following an attack of measles,
patients with NS might have long-term remission.4 It is
now believed that a disturbance in the Th1 and Th2
immune mechanisms, mediated by cytokines, is involved
in the pathogenesis of NS. 5, 6, 7 These observations
represent the scientific rationale for use of cytotoxic and
immunosuppressive drugs in childhood NS.
Arniel first proposed the use of prednisolone in
children with NS.8 Subsequently the International Study
of Kidney Disease in Children (ISKDC) proposed 60 mg/
m2/day of prednisolone for induction of remission of NS,
which has been accepted as standard treatment. 9
Although a majority of children will respond to
corticosteroid therapy, this therapy is not curative, and
most patients relapse. Each relapse is associated with an
increased risk of morbidity and mortality from infection,
thromboembolism and hypovolemic shock.2, 10, 11
Steroid toxicity is a major cause for concern in children
with NS and their families. In 1967, cyclophosphamide
(CYC) was reported as an effective agent in maintaining
sustained remission in steroid sensitive NS. 12, 13 Side
effects of CYC have been a cause for concern, including
alopecia, bone marrow suppression and opportunistic
infections, hemorrhagic cystitis and long-term risk of
malignancy and infertility. 14, 15 In the mid 1980’s,
levamisole (LEV) and calcineurin inhibitor cyclosporin A
(CSA) were used with variable success. While the
reported side effects with LEV therapy are low,16, 17 the
side effects of CSA include hirsutism, gingival
hypertrophy and nephrotoxicity.

Indian Journal of Pediatrics, Volume 72—September, 2005 763

 Abeyagunawardena A.S.

This article reviews the current approach to the seen as a complication of hypovolemia. If the plasma
therapy of NS in childhood, with emphasis on the use of volume is contracted, then anti-diuretic hormone is
corticosteroid and other immunosuppressive agents. secreted in response to the baroreceptor stimulation
leading to water retention and dilutional hyponatremia.
INITIAL LABORATORY EVALUATION
Calcium
Urine
Urine deposits The total plasma calcium concentration is low in parallel
to the reduction of albumin level as it is partly albumin
Transient microscopic hematuria is found in 23% patients
bound. However, the ionized calcium concentration is
with steroid sensitive MCD.1 Persistence of microscopic
normal and it is not necessary to treat the low total
hematuria is more indicative of FSGS but this should not
calcium concentration that eventually returns to normal
be used to discriminate between the two. The presence of
with normalization of albumin concentration.
macroscopic hematuria is suggestive of more aggressive
forms of glomerulonephritis.1
DEFINITIONS
Urine protein
Nephrotic syndrome: Edema, hypoalbuminemia (< 25 g/l)
The ISKDC definition of NS in children is proteinuria
and proteinuria > 40 mg/m2/hour or protein/creatinine
greater than 40 mg/m2/hour in an overnight specimen of
ratio > 1.8 mg/mg
urine, which is equivalent to 1.7 g/24 hours in adults.
Remission: Urinary protein excretion < 4 mg/m2/hour
Some experts suggest that nephrotic range proteinuria be
or reagent strip (Albustix) negative or trace for three
defined as greater than 100 mg/m2/hour.18 Timed urine
consecutive days
collections in children can be cumbersome and urine
Relapse: Urinary protein excretion > 40 mg/m2/hour or
protein : creatinine or albumin : creatinine (U Alb : UCr )
albustix 3+ or more for three consecutive days having
ratios provide a convenient approximation. UAlb : UCr of
previously being in remission
400 mg/mmol (3.5 mg/mg) or urine protein : creatinine
Frequent relapses: Two or more relapses during the first
ratio of 200 mg/mmol (1.8 mg/mg) indicate nephrotic
6 months after the initial episode or four or more relapses
range proteinuria.19
within any 12- month period
Urine sodium Steroid responsive: Remission achieved with steroid
therapy alone
Measurement of the urinary sodium concentration is a
Steroid dependence: two consecutive relapses occurring
valuable tool for the diagnosis of suspected hypovolemia,
during corticosteroid therapy or within 14 days after its
which leads to renal sodium retention. A urinary sodium
cessation.
value less than 10 mEq/l is diagnostic of intravascular
Steroid resistance: Failure to achieve remission
volume contraction, while a value above 20 mEq/l makes
following 4 weeks of daily prednisolone at 60 mg/m2/
it unlikely. However, this is not applicable if the child has
day
received potent diuretics such as frusemide.
Blood Investigations MANAGEMENT
Proteins
General Measures
Hypoalbuminemia (< 25 g/dL) is essential for the
diagnosis of nephrotic syndrome. IgG levels were also Diet
reduced, but to a lesser degree than the albumin, and IgM In the past, both low and high protein diets have been
is usually elevated. Plasma complement proteins, namely recommended for SSNS. A low protein diet reduces
the C3 and C4 fractions are usually not altered, which albuminuria but increases the risk of malnutrition.
help to differentiate SSNS from other forms of NS. Animal studies show that high protein diets increase the
synthesis of albumin, but do not increase the albumin
Lipids
concentration or growth significantly. Based on current
Total plasma cholesterol, low-density and very low- evidence, no specific dietary advice is necessary for
density lipoproteins are grossly elevated, while high- uncomplicated cases of SSNS. Modest salt restriction is
density lipoproteins remain within the normal range. beneficial during severe relapses, especially in patients
with edema.
Creatinine, urea and electrolytes
Activity
Plasma creatinine and urea concentrations are usually
normal at presentation in SSNS, but mild to moderate All efforts should be taken to actively mobilize the child;
increases may result from hypovolemia and renal bed rest should be avoided if possible to minimize the
underperfusion. Plasma electrolytes too are usually risk of thrombosis.
normal at presentation but hyponatremia is occasionally

764 Indian Journal of Pediatrics, Volume 72—September, 2005

 Treatment of Steroid Sensitive Nephrotic Syndrome
Immunizations
All killed vaccines are generally regarded as safe for
administration when a child is in remission. However,
relapses are noted to cluster following meningococcal C
conjugate vaccination program in the United Kingdom.20
Caution should be exercised and parents counseled
regarding the risk of relapse before administering this
vaccine. All live vaccinations should be avoided until
children are off daily steroids for at least 6 weeks.
Additionally, they should be avoided where
cyclophosphamide or cyclosporine A therapy has been
initiated.1
Complications
Infections
Children with NS are at a higher risk of infection, partly
because of the disease itself and partly due to
immunosuppressive therapy. They have a strong
predilection for pneumococcal infections. Some experts
propose that children with NS be administered oral
penicillin prophylaxis during a relapse of the disease.1 It
is important to remember that gram-negative bacteria
cause a significant proportion of infections in children
with NS, and until an organism has been identified in a
particular patient, broad-spectrum antibiotics should be
prescribed. Patients on immunosuppressive medications,
if exposed to varicella infection, should preferably receive
the zoster immunoglobulin within 72 hours. Patients who
develop varicella should be treated with intravenous
acyclovir.1
Hypovolemia
Hypovolemia and shock generally occur with the
development of edema. Fluid loss during diarrhea,
vomiting, sepsis and injudicious diuretic therapy might
precipitate development of hypovolemia. Clinical signs
and symptoms include severe central abdominal cramps
with or without vomiting, reduced urine output, cold
extremities, low blood pressure or reactive hypertension.
Laboratory findings of low urinary sodium (< 10 mEq/l)
and increased hematocrit suggest impending
hypovolemic shock. Prompt treatment is essential and
colloid infusion is the mainstay of treatment; 4.5%
albumin, 20% albumin or plasma should be infused
slowly under careful monitoring. If evidence of
pulmonary edema develops, the infusion should be
stopped and intravenous frusemide (1 mg/kg)
administered.
Hypertension
In SSNS, the blood pressure is usually normal. However,
hypertension in children with SSNS should be evaluated
very carefully. It may reflect hypervolemia or extreme
vasoconstriction in response to hypovolemia mediated via
the renin-angiotensin system. In the latter, urinary
sodium will be very low. If blood pressure exceeds the
Indian Journal of Pediatrics, Volume 72—September, 2005
normal limit, a short course of antihypertensives could be
prescribed once hypovolemia is excluded. Commonly
used antihypertensive medications are nifedipine,
hydralazine or atenolol. Diuretics are useful when
hypertension is due to fluid overload.
Thrombosis
Children with NS are prone to develop both arterial and
venous thrombosis. The propensity for thrombosis is due
to a combination of hemodynamic factors and
hypercoagulable state associated with NS. This, along
with loss of anti-thrombin 1 in urine, increases the risk of
thrombosis in children with NS.10 The usually affected
sites are the deep veins of the legs and pelvis, mesenteric
veins and pulmonary vasculature.
Acute renal failure
Acute renal failure rarely complicates SSNS, but a mild
degree of prerenal azotemia is seen in association with
hypovolemia which responds to volume replacement.
Acute renal failure unresponsive to volume replacement
with histological appearance of acute tubular necrosis is
encountered occasionally with SSNS. Affected individuals
usually make complete recovery but dialysis may be
required if renal failure persists for a longer duration.
Malnutrition
Children with refractory NS may develop nutritional
deficiencies due to poor intake and malabsorption due to
gut edema. The effects of poor nutrition may be masked
by fluid retention and will be evident only with the
resolution of edema.
Hyperlipidemia
One of the cardinal features of NS is hyperlipidemia,
characterized by elevated total cholesterol, low-density
lipoproteins and very low-density lipoproteins. Whether
intermittent hyperlipidemia associated with SSNS
increases the risk of future atherosclerosis remains to be
determined, and at present, the routine use of lipid
lowering drugs is not recommended.
Refractory edema
While awaiting steroid induced diuresis, edema could be
controlled by the judicious use of diuretics (frusemide 1-
2 mg/kg, spironolactone), once hypovolemia is excluded.
In difficult cases 20% albumin or plasma could be infused
along with diuretics (frusemide).
Indications for Renal Biopsy
In practice, renal histology is less important than the
response to corticosteroid therapy. Renal biopsy is
performed only when there are features that suggest
histology other than MCD or later when there is steroid
resistance.1
The indications for renal biopsy are:
765
 Abeyagunawardena A.S.
Before treatment
1. Onset < 6 months of age
2. Initial macroscopic hematuria
3. Persistent microscopic hematuria with hypertension
4. Acute renal failure not attributable to hypovolemia
5. Low plasma C3 level
A biopsy is discretionary if: (a) onset is between 6-12
months of age, (b) onset above 14-16 years or (c) there is
persistent hypertension, microscopic hematuria
Post treatment
A renal biopsy is recommended in all patients with
steroid resistance. It is discretionary in frequently
relapsing disease before commencing second line
drugs (especially CSA).
SPECIFIC THERAPY
Induction of Remission
Corticosteroids
Corticosteroids remain the drug of first choice for
induction of remission. While there are no controlled
trials that have compared the efficacy of prednisone with
prednisolone, both medications are comparable.
The treatment protocol, prednisolone 60 mg/m2 daily
in divided doses for 4 weeks followed by 40 mg/m2 / day
prednisolone for 3 consecutive days of a week
(intermittent) for the next 4 weeks, designed by ISKDC
over 35 years ago was empirical. 9 However, current
practice is to prescribe alternate day therapy in the second
month of treatment in preference to intermittent therapy
because it reduces the relapse rate more effectively.21 In
the past 20 years there has been considerable debate
regarding the optimization of the initial corticosteroid
protocol. Several controlled studies have examined the
effects of the duration of prednisolone therapy in relation
to long-term outcome. Shorter prednisolone courses are
associated with a higher rate of relapse. In contrast,
significantly greater sustained remission was achieved by
intensifying the initial steroid therapy.22 Meta-analysis of
randomised controlled trials suggests that the total
duration of corticosteroid therapy should exceed that
used in the ISKDC regimen.23 The relative risk of relapse
at 12-24 months falls by 0.133 (13%) for every month of
increase in therapy for seven months. 23 However, the
clinical usefulness of this reduction in terms of reducing
the incidence of steroid dependent disease and in the use
of second-line immunosuppressive agents such as
cyclophosphamide and cyclosporine remain unclear.
Long-term therapy may also be associated with a higher
risk of side effects.
Overall, the optimal initial dose and the duration of
corticosteroid therapy that is most beneficial for the
induction of sustained remission with minimal side
effects remain controversial. Therefore until results of
more controlled trials are available, remission should be
766
induced with prednisolone 60 mg/m2/24 hours as a
single morning dose and continued for 4-6 weeks,
irrespective of the timing of remission, followed by a
tapering regimen of alternate day prednisolone for a
further 6 weeks in order to achieve sustained remission.24
Treatment of Relapses
The characteristic feature of SSNS is tendency to relapse.
Intensification of relapse treatment with prednisolone has
little effect on the subsequent relapse rate.25 The response
to steroids is much better in relapses when compared to
the initial episode.1 Induction of remission is achieved
with prednisolone 60 mg/m 2/day as for the initial
episode, followed by alternate day prednisolone for a
further 4-6 weeks.24 In spite of the report of induction of
remission achieved with prescription of prednisolone,26
such therapy could lead to difficulties in defining children
who develop secondary steroid resistance and therefore is
not recommended.
Children with a frequently relapsing disease or steroid
dependent disease need individualized treatment.1, 24
Although there is no data on the merits of long term
maintenance, there is prednisolone as opposed to
repeated standard relapse treatment, and most pediatric
nephrologists favor the former approach.1, 24 The dose
should be titrated to the lowest level possible, sufficient to
maintain remission in order to minimize steroid side
effects. Most primary school children can tolerate 0.1-0.6
mg/kg/body weight on alternate day while most
preschool children will tolerate up to 1mg/kg/body
weight on alternate days.1, 24 The duration should be for a
minimum of 3-6 months as alternate day therapy,
although a selected group of children may benefit from
long-term alternate day treatment.
Steroid toxicity
The side effects of steroids are numerous, well-recognized
and of great concern to the patient as well as the family.
There was a positive correlation between the side effects
and cumulative dose of steroids in children with an initial
episode of SSNS. 27 Obesity, hirsutism, arterial
hypertension and psychological disturbances are usually
reversible after cessation of steroid therapy. 27 However,
striae and cataracts are not reversible.27 Growth failure
was observed only in children with prolonged daily
steroid therapy, while alternate day steroids were not
associated with significant growth impairment.28, 29 In
order to prevent toxicity, patients on long term steroid
therapy should be reviewed every 3 months for blood
pressure and growth measurements and annually for
development of cataracts.1
Cytotoxic Therapy
SSNS represents a milder form of the disease and a
majority of children could be controlled with
corticosteroid therapy. 30, 31 Children with frequently
relapsing or steroid dependent disease who show steroid
Indian Journal of Pediatrics, Volume 72—September, 2005
 Treatment of Steroid Sensitive Nephrotic Syndrome

toxicity are the candidates for treatment with alkylating after cessation of treatment. 41 Long lasting remissions
agents or other immunomodulatory drugs. were obtained when CSA was prescribed continuously
for 5 years.41 CSA is a difficult drug to use and requires
Cyclophosphamide
monitoring of blood concentrations and regular
Over the past 30 years, CYC has been used for the measurement of the glomerular filtration rate because of
treatment of childhood NS. It has been effective in its potential nephrotoxicity.40, 41
inducing sustained remission in frequently relapsing NS
Other Immunosuppressive Drugs
(FRNS), steroid dependent NS (SDNS) and inducing
remission in SRNS. 14 The initial strategy in cytotoxic
treatment using CYC was an increase of daily dosage at First episode of
biweekly intervals until neutropenia developed and at Nephrotic synrome
which point CYC was abruptly discontinued. CYC given
orally in a dosage of 3 mg/kg/day for 8 weeks induced
sustained remission in 69% at one year and 44% at five
years in SSNS. 12 However, in subsequent studies the
proportion of sustained remission induced varied Trial of daily steroids (4-6 weeks)
considerably. 32 In spite of this, meta-analysis of
randomized controlled trials suggests that CYC is useful
in inducing sustained remission in SDNS.32 Although it
was reported that prescription of CYC 2 mg/kg/day Response
orally for 12 weeks achieved a higher proportion of
sustained remission, 33 subsequent studies failed to
confirm this finding.34 A shorter regimen of CYC for 2 Tapering alternate
weeks was associated with a higher relapse rate. 35 No relapse day steroids for Relapse
Intravenous pulsed CYC at 600 mg/m2 monthly for six 6-12 weeks
months is being increasingly used with variable success
for SDNS. 36, 37 Most studies include small number of
patients and therefore it is difficult to interpret the
advantages over oral therapy. Relapse following CYC is Repeat short
generally treated with steroids. Second course of CYC is steroid course
effective in inducing long-term remission.31 As the long-
term side effects of CYC are cumulative, such therapy
should be reserved for select patients. Response of CYC in Frequent relapse
SRNS is unpredictable, and the information from or steroid Infrequent relapse
literature is limited. Steroid resistant MCNS is usually dependence
responsive to CYC and there is a tendency for the
subsequent relapses to become steroid responsive.38
Chlorambucil Alternate-day Intermittent
steroids 6-12 short steroid
Chlorambucil (CHL) can induce a prolonged steroid free courses
remission in children with FRNS or SDNS and its efficacy months
is similar or even better than CYC. As with CYC, its long-
term toxic effects limit its prolonged or continuous use.
The dosage used is 0.2 mg/kg/day for 8-12 weeks.39 The Poor control or Steroids
risk of hematological malignancy is greater with CHL steroid toxicity well tolerated
than with CYC.20
Cyclosporine A
Sustained Levamisole or Taper alternate
In SSNS, cyclosporine A (CSA) is generally reserved for
remission cyclophosphamide day steroids
children who become steroid dependent following a
course of cyclophosphamide.31, 40, 41 It is now increasingly
used in preference to CYC in children approaching
puberty, especially boys who are more vulnerable for Consider:
No sustained Cyclosporin A,
testicular damage from CYC and in whom the disease remission MMF Vincristine, etc.
does not have a long run.41 CSA is generally prescribed at
a dosage of 3-5 mg/kg/day for a period of one year.31,40, 41
Unlike CYC or CHL, CSA loses its protective effectiveness Fig. 1. Suggested Plan for Managing a Child with SSNS

Indian Journal of Pediatrics, Volume 72—September, 2005 767

 Abeyagunawardena A.S.
Nitrogen mustard, azathioprine, tacrolimus,
mycophenolate mofetil and vincristine have been tried
with variable success but did not gain a great deal of
popularity as a result of the initial successful results with
CSA. However, success rates and the side effect profile of
both vincristine 42 and mycophenolate mofetil 43 are
encouraging and they are likely to emerge as attractive
steroid sparing agents.
Immunomodulatory Drugs
Levamisole (LEV) is an antihelminthic drug which is an
immunostimulant. It has been successfully used at a
dosage of 2.5 mg/kg on alternate days alone or in
conjunction with alternate day prednisolone for FRNS
and SDNS.16 The major advantage of LEV is its steroid
sparing effect, with minimal side effects. LEV is less
effective when used alone than in combination with
corticosteroids. It is not clear from the literature how
prednisolone should be withdrawn during LEV therapy
in order to minimize the risk of relapse. Although a
controlled trial questioned the early positive findings of
LEV therapy,44 a recent report where LEV therapy was
extended to 2-3 years reduced the number of relapses per
patient from 5.2 to 0.65 in the first year.45
Toxicity of Cytotoxic Drugs
Toxicity of alkylating agents has been well known for
many years and includes short term as well as long-term
side effects. Bone marrow suppression with neutropenia,
lymphopenia and thrombocytopenia, alopecia, nausea,
abdominal pain and discomfort, hemorrhagic cystitis and
increased risk of malignancy constitute the short term
side effects, while long term side effects include increased
risk of future malignancy and potential gonadal toxicity.15
Arterial hypertension, hypertrichosis, gingival
hyperplasia, hypomagnesemia, hyperuricemia and
nephrotoxicity may be encountered during CSA
therapy.41
A particular concern regarding the use of cytotoxic
drugs is the long-term cancer risk, but this risk has not
been quantified in children.15 There is a general paucity of
data regarding cumulative dose toxicity for the various
agents mentioned above, and this is an important factor to
bear in mind and should be discussed with parents and
children before the initiation of therapy. Other potential
medium and long-term side effects such as teratogenicity
and infertility are also important considerations, but they
rarely become major concerns at the doses and durations
of cytotoxic immunosuppression employed in the
treatment of childhood NS.15
Cytotoxic and immunosuppressive drugs
undoubtedly play an important role in the treatment of
certain forms of childhood NS, even though these drugs in
themselves are associated with significant rates of
morbidity and even mortality. It is therefore of particular
importance that the benefits and risks of these agents are
meticulously balanced before considering their use in the
768
treatment of patients with NS. This point is worthy of
emphasis since majority of children with SSNS will
outgrow the disease around puberty irrespective of
therapy.
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Notes and News

Conference on Inborn Errors of Metabolism

Workshop: 28 to 30 Sept 2005
Symposium: 1 and 2 October 2005

Sir Ganga Ram Hospital, New Delhi

An event that will change the scene for IEM in India.

Faculty of Outstanding International Experts in Metabolic Diseases

• Dr Joe T. Clarke, from Canada author of the best selling book –“Clinical Guide to Inherited
Metabolic Diseases”.
• Dr Robert Desnick, Professor of Human Genetics at Mt. Sinai School of Medicine, New
York, USA – a pioneer in enzyme therapy.
• Dr C. Auray-Blais, from Canada - Chromatography for amino acids and organic acids.
• Y. Shigematsu from Japan – Leader in Tandem Mass Spectrometry.
• T. Ohashi from Japan - Expert in gene therapy.
• P. Kishnani, Director, Metabolic Clinic, USA.

All leading Experts in Metabolic Disorders in India – Prof. S.S. Agarwal (Lucknow), Prof. K Taranath
Shetty (Bangalore), Dr Radha Rama Devi (Hyderabad), Dr Ananth Rao (Kochi), Dr Madhulika Kabra
(Delhi), Dr Mamta Muranjan (Mumbai), Dr Manjeet Kaur (Delhi), Dr I.C. Verma (Delhi).

Registration fees:
Before 31st July 2005 After July Spot Registration
th th
Workshop (28 -30 Sept.) – Rs 2500 Rs 3000 Nil
Conference (1st & 2nd Oct.) – Rs. 1000 Rs 1500 Rs 2000

Send your registration fees in the name “Sir Ganga Ram Hospital” at the following address:
Dr I.C. Verma, Department of Genetic Medicine, Sir Ganga Ram Hospital, Rajinder Nagar,
New Delhi - 110060.
Tel. and fax: +91-11-25861767; E-mail: dr_icverma@yahoo.com

770 Indian Journal of Pediatrics, Volume 72—September, 2005