Case presentation
A seven-year-old boy, presumed case of ataxia-telangiectasia, was
referred to our pediatric immunology clinic by a pediatric neurologist
for further workup due to ocular involvement. He was born from
non-consanguineous parents, gravid four, with a history of developmental
delay in the previous child but no history of abortion or death. The
proband weighed 3.5 kg at birth (full-term), at which time asphyxia did
not occur. At the age of eight months, the parents became concerned
about a delay in sitting and standing, but neuroimaging was normal
without any evidence of cerebellar or vermian hypoplasia or other
anomalies. He developed telangiectasia in the eyes at 15 months of age,
at which time vision problems also manifested. He had a delay in global
development and speaking; by four years, he could only correctly say one
or two words. The convulsion history was negative. Due to his attention
disorder, methylphenidate and risperidone were prescribed for him at the
age of five.
At seven years of age, he had a weight of 29 kg (+2 standard deviations
[SD]), a height of 120 cm (−1 to 0 SD), with a head circumference of
52 cm (−1 SD). Our physical examination revealed slight facial
coarseness, mildly deep-set eyes, round nasal tip, full cheeks and thick
lips (Fig. 1), central hypotonia, and ataxia. Deafness, ichthyosis, and
hand stereotypes were not noted.
Our ophthalmologic consultant reported pigmentary retinopathy with optic
disc paleness on examination of the fundus. Telangiectasia and nystagmus
were also reported, though ocular coloboma was not seen. The
visual-evoked potential demonstrated an extinguished response.
On laboratory workup, routine hematology and biochemical tests
(renal/hepatic function) were normal, as were the essential metabolic
screening, arterial lactate, and blood ammonia. Interestingly, the
insulin-like growth factor (IGF)-1 level was normal Other normal tests
included an electroencephalogram, the brainstem-evoked potential, a
karyotype study, and chromosomal microarray.
Considering the patient’s clinical manifestations (pigmentary
retinopathy, hypotonia, ataxia, and telangiectasia), we suspected
congenital disorders of glycosylation (CDG) and requested serum
isoelectric focusing and whole-exome sequencing. Exome sequencing
identified the presence of homozygous pathogenic variant
c.57G>A (p.Trp19Ter) in the SRD5A3 gene. The
mutation was confirmed by Sanger sequencing, and the diagnosis of
SRD5A3-CDG was established.