A rare case of SRD5A3-CDG in a patient with ataxia and telangiectasia: A case report.
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SUBMITTER: Nabavizadeh SH
PROVIDER: S-EPMC9684675 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
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A rare case of SRD5A3-CDG in a patient with ataxia and telangiectasia: A case report.
Nabavizadeh Sayyed Hesamedin SH Noeiaghdam Rafat R Johari Leila L Hosseini Seyed Ali SA Esmaeilzadeh Hossein H Alyasin Soheila Sadat SS
Clinical case reports 20221123 11
Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is an extremely rare congenital disease. Common manifestations are developmental delay, intellectual disability, ophthalmological abnormalities, cerebellar abnormalities, ataxia, and hypotonia. Here, we discuss a seven-year-old boy with SRD5A3-CDG (homozygous variant c.57G>A [p.Trp19Ter]), featuring the unprecedented finding of telangiectasia. ...[more]
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Project description:Background: SRD5A3-CDG is a rare N-glycosylation defect caused by steroid 5 alpha reductase type 3 deficiency. Its key feature is an early severe visual impairment with variable ocular anomalies often leading to diagnosis. Additional symptoms are still poorly defined. In this case study, we discuss 11 genetically confirmed cases, and report on emerging features involving other systems in addition to the eye phenotype. Methods: In total, 11 SRD5A3-CDG patients in five sets of sibships were included in the study. Data on 9 of 11 patients are as of yet unpublished. Patients' results on biochemical and genetic investigations and on in-depth phenotyping are presented. Results: Key diagnostic features of SRD5A3-CDG are ophthalmological abnormalities with early-onset retinal dystrophy and optic nerve hypoplasia. SRD5A3-CDG is also characterized by variable neurological symptoms including intellectual disability, ataxia, and hypotonia. Furthermore, ichthyosiform skin lesions, joint laxity, and scoliosis have been observed in our cohort. We also report additional findings including dystonia, anxiety disorder, gastrointestinal symptoms, and MRI findings of small basal ganglia and mal-rotated hippocampus, whereas previous publications described dysmorphic features as a common finding in SRD5A3, which could not be confirmed in our patient cohort. Conclusion: The detailed description of the phenotype of this large cohort of patients with SRD5A3-CDG highlights that the key clinical diagnostic features of SRD5A3-CDG are an early onset form of ophthalmological problems in patients with a multisystem disorder with variable symptoms evolving over time. This should aid earlier diagnosis and confirms the need for long-time follow-up of patients.
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Project description:Ataxia telangiectasia (A-T) is a common, genetically inherited cause of early childhood-onset ataxia that is classically characterized by progressive cerebellar malfunction, oculocutaneous telangiectasia, genome instability, and immunodeficiency. There is vast phenotype variation in patients with A-T and recently, dystonia, an extrapyramidal movement disorder. Here, we report the case of a 10-year-old girl who had experienced repeated diarrhea and mild gait ataxia since the age of two years. At age seven, ataxia and ocular telangiectasia were evident and immunoglobulin level assessment showed hyper IgM immune phenotype, thus a diagnosis of A-T was made based on clinical and laboratory findings, and she was started on intravenous immunoglobulin therapy. Generalized dystonia appeared when she was 10-years-old. Molecular analysis revealed two heterozygous mutations, c.6259delG and c.6658C>T, in the ATM gene of which one (c.6259delG) is novel. Dystonia can be part of the clinical picture in the A-T disorder and may even mask ataxia. This should be considered as a major feature mainly in variant A-T, which may occur without general ataxia and may be misdiagnosed in adults with primary dystonia.
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Project description:BackgroundSRD5A3 is responsible for SRD5A3-CDG, a type of congenital disorder of glycosylation, and mutations have been reported in 15 children. All the mutations are recessive and truncating.Case presentationWe present 2 brothers at the age of 38 and 40 years with an initial diagnosis of cerebellar ataxia. We found the candidate disease loci via linkage analysis using data from single nucleotide polymorphism genome scans and homozygous truncating mutation SRD5A3 p.W19X, which was previously reported in 3 unrelated children, by exome sequencing.Clinical investigations included physical and ocular examinations and blood tests. Severe ocular involvement with retinal bone spicule pigmentation and optic atrophy are the most prominent disabling clinical features of the disease. The serum transferrin isoelectric focusing (TIEF) pattern is abnormal in the patient investigated.ConclusionOur patients are older, with later onset and milder clinical phenotypes than all patients with SRD5A3-CDG reported so far. They also have atypical ocular findings and variable phenotypes. Our findings widen the spectrum of phenotypes resulting from SRD5A3 mutations and the clinical variability of SRD5A3-CDG, and suggest screening for SRD5A3 mutations in new patients with at least a few of the clinical symptoms of SRD5A3-CDG.
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