The document presents a case report of a 6-year-old boy diagnosed with infantile cystinosis after being misdiagnosed with renal rickets. Key historical details, including family history and symptoms like severe photophobia, led to the correct diagnosis and initiation of appropriate treatment with cysteamine. This case emphasizes the importance of thorough patient history in diagnosing rare conditions to improve treatment outcomes.

1. Cystinosis: An “eye opener”

2. a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1 e3
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Case Report
Cystinosis: An “eye opener”
Krishnan Swaminathan a,*, Murugan Jeyaraman b
a
b
Consultant Endocrinologist, Department of Endocrinology, Apollo Specialty Hospital, 625 020 Madurai, India
Consultant Paediatrician, Department of Paediatrics, Apollo Specialty Hospital, 625 020 Madurai, India
article info
abstract
Article history:
A much-quoted aphorism in medicine is “Listen to your patient and they are telling you the
Received 3 January 2014
diagnosis”. Most often, the history reveals the diagnosis and sometimes, it is all that is
Accepted 21 January 2014
required to make the diagnosis. Unfortunately, in this age of modern technology-based
Available online xxx
medicine, many busy clinicians fail to get a proper history and miss important dots in
the history that connect to the diagnosis. This is clinically relevant, as a specific diagnosis
Keywords:
completely alters the nature of treatment and thereby improves prognosis. We present a
Short stature
young boy with infantile cystinosis, who was evaluated in at least three tertiary referral
Cystinosis
centers prior to our review and branded as having “renal rickets due to a posterior urethral
Renal failure
valve”. Two important clues from history that clinched a clinical diagnosis of infantile
cystinosis in this boy with renal rickets were the father’s comment that “His elder daughter
died at 7 years of age with a similar condition” and the mother’s complaint that “her son
cannot see television properly, his eyes become red and tears roll through his eyes”. Our
aim is to open the eyes of medical community to this rare but treatable condition, especially in young children presenting with renal rickets, photophobia and short stature.
Copyright ª 2014, Indraprastha Medical Corporation Ltd. All rights reserved.
1.
Case report
We report a 6-year-old boy born of consanguineous parents.
His birth history was normal. At nine months of age, he presented with polyuria and polydipsia, in the absence of hyperglycemia. For the next five years, he was investigated in
three different tertiary referral centers in South India for
stunted growth and renal rickets. He was finally branded as
having “renal osteodystrophy due to a posterior urethral
valve”. Treatment consisted of sodium bicarbonate tablets
and calcitriol 0.25 once daily, with poor compliance with both
the medications. At our clinic visit, we found a lethargic boy
with a height centile of <3% with features of renal rickets and
dryness of skin (Fig. 1). Abdomen was distended with mild
hepatomegaly. Further detailed family history revealed that
his elder sister had died at seven years of age with stunted
growth, rickets and renal failure. Another important piece of
history came from the boy’s mother who commented that
“the only pastime for him is to watch television but nowadays,
he gets severe irritation in his eyes with redness and persistent watering”. A PubMed search with “short stature, renal
rickets and photophobia” gave three hits, all pointing towards
a diagnosis of infantile cystinosis.
Further lab work up revealed severe primary hypothyroidism with a Thyroid stimulating hormone (TSH) > 150 mIU/
L and undetectable free thyroxine (FT4). He had renal
impairment with low serum calcium, phosphate, grossly
elevated parathormone (PTH) and alkaline phosphatase.
* Corresponding author. Tel.: þ91 8526421150; fax: þ91 4522580199.
E-mail address: k_swaminathan@hotmail.com (K. Swaminathan).
0976-0016/$ e see front matter Copyright ª 2014, Indraprastha Medical Corporation Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.apme.2014.01.002
Please cite this article in press as: Swaminathan K, Jeyaraman M, Cystinosis: An “eye opener”, Apollo Medicine (2014), http://
dx.doi.org/10.1016/j.apme.2014.01.002

3. 2
a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1 e3
apparently homozygous state in exon 7: c.422C > T responsible for the replacement of serine by phenylalanine at position 141 on the protein p.Ser141Phe (Fig. 2), in agreement with
a diagnosis of cystinosis.
The child was started on supportive measures, indomethacin, phosphate and increased dose of calcitriol. With great
difficulty, we managed to get Cysteamine (Cystagon), a drug
that directly treats the disease by reducing the intracellular
cystine content. This drug is very expensive, not available in
India and had to be imported from France (Orphan Europe,
http://www.orphan-europe.com). To this date, he has tolerated the drug well. Photophobia has improved remarkably
with Cysteamine eye drops (Cystagon 0.5%) six times per day.
He has been referred to the regional renal transplant team,
who have previous experience with a similar boy aged 7 years
with infantile cystinosis.
Fig. 1 e Evidence of rickets and dryness of skin due to
severe primary hypothyroidism.
2.
Serum Insulin like Growth Factor-1 (IGF-1) was within normal
limits. An ophthalmologist referral revealed extensive corneal
micro deposits. Blood samples were sent for molecular genetic
analysis to Groupement Hospitalier Est, France. DNA was
extracted from leucocytes (Nucleon BACC3 kiteGE Healthcare). Screening for the common 57-kb deletion as well as
direct sequencing after PCR (Polymerase Chain Reaction)
amplification of the 12 exons of the CTNS gene was carried
out. The child was detected to have a mutation in an
Discussion
We report a case of infantile cystinosis where the main clue to
the diagnosis was marked photophobia. An accurate diagnosis resulted in appropriate treatment with marked clinical
improvement, genetic counseling and a reason for the family
to be at peace to know the reason for their son’s illness and
their daughter’s death.
Cystinosis is a rare autosomal recessive metabolic disorder
characterized by defective lysosomal efflux of cystine.
This leads to accumulation of cystine in multiple organs,
Fig. 2 e Mutation in an apparently homozygous state in exon 7: c.422C > T responsible for the replacement of serine by
phenylalanine at position 141 on the protein p.Ser141Phe.
Please cite this article in press as: Swaminathan K, Jeyaraman M, Cystinosis: An “eye opener”, Apollo Medicine (2014), http://
dx.doi.org/10.1016/j.apme.2014.01.002

4. a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1 e3
progressing to severe organ dysfunction, especially end-stage
renal failure.1 The first clinical signs usually appear at three to
six months of life and by six months, most children have fullblown renal Fanconi syndrome (glycosuria, aminoaciduria,
phosphaturia, metabolic acidosis). The clinical manifestations
include polyuria, failure to thrive, growth retardation, developmental delay, rickets, constipation and acute dehydration
episodes.2
Predominant extra-renal organs affected by cystine deposition are eyes, thyroid and liver. Cystine deposits in the
conjunctivae and cornea cause photophobia, blepharospasm
and watering of eyes. The deposits can be easily seen on slit
lamp examination. Hemorrhagic retinopathy and visual
impairment are late complications of this disease.3 Growth
retardation is a common feature of this condition. This may be
due in part to severe hypophosphatemia but hypothyroidism
may be an additional factor as well, especially in older children, where the rates are close to 70% in children more than 10
years of age. Enlarged Kupffer cells with cystine crystals
contribute to hepatomegaly and may lead to portal hypertension.4 Muscular and neurological involvements are late
complications of the disease contributing to significant
morbidity. Such patients are usually older than twenty years.
Presenting features include pseudo bulbar palsy, cerebellar,
pyramidal signs and encephalopathy associated with strokelike episodes.5
The definitive treatment of infantile cystinosis includes
Cysteamine therapy and renal transplantation for end stage
renal disease. Cysteamine therapy should be started as soon
as the diagnosis is confirmed. This drug reduces cystine
accumulation in cells and when started early, delays the
development of renal failure, hypothyroidism and improves
growth.6,7 For children up to the age of 12 years, Cystagon
(cysteamine) dosing should be based on the body surface area,
the recommended dose being 1.30 g/m2/day of the free base
divided four times a day. In children over age 12 years and
>50 kg in weight, the recommended dose is 2 g/day divided
four times a day (Courtesy: Cystagon SPC leaflet, Orphan
Europe). The goal of therapy is to keep the leukocyte cystine
levels to <1 nmol hemicystine/mg protein. Unfortunately, we
do not have access to leukocyte cystine levels and therefore
have to continue treatment for our case based on clinical
response. It is important to remember not to exceed the dose
of cysteamine to higher than 1.95 gm/m2. Renal transplantation is a definitive option for children with end stage
renal disease as cystine induced tubular dysfunction does not
3
recur on the graft. However, this has to be balanced against
long-term morbidity from immunosuppression and extrarenal cystinosis.8
To summarize, infantile cystinosis can be easily missed.
We hope that this instructive case is an “eye opener” for the
medical community to think about this rare but treatable
disease in the appropriate clinical context.
Conflicts of interest
All authors have none to declare.
Acknowledgments
We wish to acknowledge Dr. Sujatha Jagadeesh, Consultant
Geneticist, Chennai and the molecular genetics work by Dr. C.
Vianey Saban and Dr. Cecile Acquaviva, France.
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´ ´ ´
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Please cite this article in press as: Swaminathan K, Jeyaraman M, Cystinosis: An “eye opener”, Apollo Medicine (2014), http://
dx.doi.org/10.1016/j.apme.2014.01.002

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