TABLE 1.
Clinical characteristics of patients with SRD5A3-CDG in our cohort of 11 patients.
| Phenotypic presentation of 11 patients with SRD5A3-CDG | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient ID/Age | 1-1/20 y | 1-2/14.9 y | 2-1/23 y | 2-2/19 y | 3-1/16 y | 3-2/8.5 y | 4-1/15 y | 4-2/12 y | 4-3/5 y | 5-1/20 y* | 5-2/17 y* | |
| Gender | F | F | F | F | F | M | F | F | M | F | M | |
| Ethnicity | Pakistani | Pakistani | Indian | Indian | Kurdish | Kurdish | Pakistani | Pakistani | Pakistani | Baluchi | Baluchi | |
| Consanguinity | + | + | + | + | + | + | + | + | + | + | + | |
| Age at onset (months) | 9 m | Birth | 18 m | Birth | 2 m | 6 m | 6 weeks | 3 weeks | 6 weeks | Birth | Birth | |
| Age at diagnosis (years) | 15 y | 2 y | 16 y | 12 y | 11 y | 4 y | 13 y | 8 y | 4 y | ∼5 y | ∼1 y | |
| Genetics | SRD5A3 c.943C > T p.(Pro315Ser) Homozygous | SRD5A3 c.943C > T p.(Pro315Ser) Homozygous | SRD5A3 c.57G > A p.(Trp19Ter) homozygous | SRD5A3 c.57G > A p.(Trp19Ter) homozygous | SRD5A3 c.57G > A p.(Trp19Ter) homozygous | SRD5A3 c.57G > A p.(Trp19Ter) homozygous | SRD5A3 c.57G > A p.(Trp19Ter) homozygous | SRD5A3 c.57G > A p.(Trp19Ter) homozygous | SRD5A3 c.57G > A p.(Trp19Ter) homozygous | SRD5A3 p.Gln96delinsX homozygous deletion | SRD5A3 p.Gln96delinsX homozygous deletion | |
| Dysmorphic features | No | No | No | No | No | No | No | No | No | Yes | Yes | |
| Ophthalmic findings | RD Squint | RD | RD, Nystagmus | RD, Nystagmus | RD Nystagmus Astigmatism | RD Nystagmus Astigmatism | RD Nystagmus | RD Nystagmus | RD Nystagmus Optic nerve hypoplasia | Squint Bilateral optic nerve colobomas | Bilateral iris and chorioretinal colobomas | |
| Neuro-development | GDD, mild LD | GDD, severe LD, ASD | GDD, LD | GDD, LD | GDD, severe LD, ASD | GDD, severe LD, ASD | GDD, moderate LD | GDD, Mild LD | GDD, severe LD | GDD, LD | GDD, LD | |
| Hypotonia | + | + | + | + | + | + | + | − | + | + | + | |
| Seizures | − | − | − | − | − | − | − | − | − | − | − | |
| Dystonia | − | − | − | − | − | + | − | − | + | − | − | |
| Behavior | − | Anxiety | − | Anxiety | Anxiety | − | Mood swings | Anxiety | − | − | − | |
| Ataxia | − | + | + | − | + | + | + | − | − | − | − | |
| Cutaneous | Psoriasis | Ichthyosis, collodion baby | − | Mild hyperkeratosis | − | − | Eczema | Dry skin | − | Ichthyosis Hypertrichosis | Ichthyosis Hypertrichosis | |
| Cardiac | Palpitations | Palpitations | − | − | AR, Prolonged QT | AR | − | − | − | TGA | sASD | |
| Gastrointestinal | IBS | IBS, cyclical vomiting | − | Unexplained weight loss | − | Constipation, dairy allergy | − | − | Poor feeding, dysphagia, Gastrostomy | − | − | |
| Renal | − | − | − | − | − | − | − | − | − | Right duplex kidney | − | |
| Infection | − | − | − | − | − | Recurrent URTI and LRTI, on prophylactic azithromycin | − | − | Recurrent LRTI Prophylactic azithromycin | − | − | |
| Endocrine | Primary Ovarian Failure | − | − | − | Irregular menstruation | − | − | − | − | Small AP, SOD | Small AP | |
| Spinal scoliosis | − | − | + | + | + | + | + | − | + | − | − | |
| Joint laxity | − | − | − | − | + | + | − | − | + | − | − | |
| Dental | − | − | − | Crowding, difficult hygiene | − | − | Dental extractions | − | Premature loss of milk teeth | − | − | |
| Investigations | ||||||||||||
| Transferrin isoelectric focusing | Abnormal type 1 pattern | Abnormal type 1 pattern | nk | Nk | Normal | Abnormal type 1 pattern | Abnormal type 1 pattern | Abnormal type 1 pattern | Abnormal type 1 pattern | Abnormal type 1 pattern | Abnormal type 1 pattern | |
| Clotting | Normal | Normal | nk | nk | Normal | Prol. APTT | nk | nk | nk | nk | nk | |
| TFT | Normal | Normal | nk | nk | Nk | Normal | nk | nk | Normal | Norm | Normal | |
| Testosterone | 3.8 (H) | Nk | nk | nk | Nk | nk | nk | nk | nk | nk | nk | |
| FSH/LH | 4.3/15.3 | 3.4/15.0 | nk | nk | Normal | nk | nk | nk | nk | nk | nk | |
| GH | Nk | Normal | nk | nk | Nk | Normal | nk | nk | nk | Norm | nk | |
| Liver test | Normal | Normal | nk | Normal | Normal | Elevated | Normal | nk | Elevated | Norm | Elevated | |
| MRI brain | Findings suggestive of demyelination | Cavum septum pellucidum et vergae, small basal ganglia, mild cerebellar hypoplasia and dysplasia, thick corpus callosum, punctate white matter lesions | Not done | Not done | Normal apart from non-specific subcortical white matter foci in the frontal lobe | Malrotation of hippocampus, retro-cerebellar cyst, thin cervical cord, immature myelin, basal ganglia small (LN) | Not done | Not done | Small cerebral white matter volume, small cerebellum and pons, delayed myelination, small basal ganglia (LN), small optic nerves, malrotation of hippocampus | Small AP, left microphthalmia and atrophic visual pathways | Cerebellar vermis hypoplasia, b/l severe frontal microgyria, delayed myelination | |
(+), present; (−), not present; (*), patients lost to follow up; RD, retinal dystrophy; GDD, global developmental delay; LD, learning difficulties; ASD, Autism spectrum disorder; AR, abnormal repolarisation; TGA, transposition of the great arteries; sASD, secundum atrial septal defect IBS, irritable bowel syndrome; URTI, upper respiratory tract infection; LRTI, lower respiratory tract infection; AP, anterior pituitary; SOD, septo-optic dysplasia; APTT, activate partial thromboplastin time; TFT, thyroid function; LN, lentiform nucleus; nk, not known.