Table 1.
Clinical presentations and etiologies of hypocalcemic seizures in 16 newborns.
| Case number | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Etiology | Digeorge syndrome | Vit. D deficiency | Digeorge syndrome | Kleefstra syndrome | Vit D deficiency | Vit D deficiency | HIE (stage I) | Vit. D deficiency | Vit. D deficiency | |||||||||
| Phenotype | HS, interrupted aortic arch, VSD | Later-onset HS | HS, imperforated anus, vascular ring | HS, ambiguous genitalia, scrotal bifida with hypospadias, penoscrotal transposition, congenital heart disease with DORV, anterior malalignment VSD, ASD, and PS | Later-onset HS, hyperphosphatemia | Later-onset HS, hyperphosphatemia | HS, hyperphosphatemia | HS, hyperphosphatemia | HS, hyperphosphatemia | |||||||||
| Lowest calcium level | 6.2 mg/dl | 6.9 mg/dl | 6.3 mg/dl | 6.9 mg/ dL | 4.3 mg/dl | 5.6 mg/dl | 7.0 mg/dl | 6.6 mg/dl | 5.7 mg/dl | |||||||||
| Duration of hypocalcemia (days) | 15 | 5 days | 10 | 4 days | 10 days | 8 days | 3 days | 14 days | 7 days | |||||||||
| Response to calcium％ | Refractory | Easy | Refractory | Easy | Refractory | Refractory y | Easy | Refractory | Easy | |||||||||
| Age of first Sz | Day 5 | Day 6 | Day 5 | Day 4 | Day 5 | Day 8 | Day 3 | Day 2 | Day 8 | |||||||||
| Age of Dx | 6 months | Day 16 | 3 months | 3 months | Day 15 | Day 14 | Day 4 | Day 15 | Day 14 | |||||||||
| Inheritance | AD | Nil | AD | AD | Nil | Nil | Nil | Nil | Nil | |||||||||
| Genotype | 22q11.2 deletion | 22q11.2 deletion | Ring chromosome 9 | |||||||||||||||
| Sex | Female | Female | Female | Male | Female | Female | Female | Male | Male | |||||||||
| Sz types | Myoclonic | Focal | Generalized tonic | Focal | Focal | Myoclonic | Focal | Focal | Myoclonic | |||||||||
| History of drugs control | IV PB, PHT, then oral TOP, pyridoxine | Calcitriol | IV PB, PHT, Calcitriol | IV PB, PHT and oral calcitriol for HS. LEV, pyridoxine for seizures after 2 years and 3 months. | PB, Calcitriol | PB, Calcitriol | PB, calcitriol | Calcitriol, calcium chloride | PB, calcitriol calcium chloride | |||||||||
| Abnormal MRI | Mild ventriculomegaly | NA | Mild ventriculomegaly | Corpus callosum hypoplasia | NA | NA | Mild ventriculomegaly. | NA | NA | |||||||||
| Neurodevelopmental outcomes | Severe delay | Unremarkable | Moderate delay | Mild delay | Unremarkable | Unremarkable | Unremarkable | Unremarkable | Unremarkable | |||||||||
| Case number | Patient 10 | Patient 11 | Patient 12 | Patient 13 | Patient 14 | Patient 15 | Patient 16 | |||||||||||
| Phenotype | HS | HS,hyperphosphatemia, hypomagnesemia, dilated cardiomyopathy, PPHN with respiratory failure | HS, hypoglycemia, growth hormone deficiency, insulin resistance | HS, high iPTH, VSD | Later-onset HS | HS, Interrupted aortic arch | Later-onset HS | |||||||||||
| Lowest Ca level | 6.9 mg/dl | 4.9 mg/dl | 6.3 mg/dl | 4.5 mg/dl | 5.6 mg/dl | 6.6 mg/dL | 6.6 mg/dl | |||||||||||
| Duration of hypocalcemia (days) | 5 days | 8 days | 8 days | 18 d | 8 days | 7day | 4 days | |||||||||||
| Response to Ca supply％ | Easy | Refractory | Refractory | Refractory | Refractory | Refractory | Easy | |||||||||||
| Age of first Sz | Day 3 | Day 6 | Day 8 | Day 2 | Day 6 | Day 5 | Day 6 | |||||||||||
| Age of Dx | Day 5 | 4 months | 4 months | 3 months | Day 15 | 4 months | Day 14 | |||||||||||
| Inheritance | Nil | AR | AR | Nil | Nil | AD | Nil | |||||||||||
| Genotype | Two alleles ALMS1 c.12118-65C>T and c.12118-65C>T (in cis) | Compound heterozygous ALMS1.c.10079C>G (p.A3360G)/ c.10323G>C (p.K3441N) | 22q11.2 deletion | |||||||||||||||
| Gender | Male | Female | Female | Male | Female | Male | Female | |||||||||||
| Sz types | Myoclonic | Focal | Focal | Generalized tonic | Focal | Focal clonic seizures | Focal seizure | |||||||||||
| History of drug control | Calcium carbonate, PB, calcitriol | IV PB, PHT, calcitriol, calcium chloride, calcium Carbonate | PB, PHT | IV PB, oral PB | Calcitriol | IV PB, PHT then oral PB, calcitriol | Calcitriol | |||||||||||
| Abnormal MRI | NA | NA | Mild ventriculomegaly | Mild ventriculomegaly | NA | NA | NA | |||||||||||
| Neurodevelopmental outcomes | Unremarkable | Unremarkable | Unremarkable | Mild delay | Unremarkable | Moderate delay | Unremarkable | |||||||||||
%Refractory hypocalcemia was defined as a hypocalcemia duration of ≥ 7 days despite calcium supply. All patients received calcium supply by intravenous calcium after the diagnosis of HS.
Sz, seizure; Dx, diagnosis; HS, hypocalcemic seizures; VSD, ventricular septal defect; DORV, double outlet right ventricle; ASD, atrial septal defect; PS, pulmonary stenosis; PDA, patent ductus arteriosus; PPHN, persistent pulmonary hypertension of newborn; AD, autosomal dominant; AR, autosomal recessive; IV, intravenous; PHT, phenytoin; OXC, oxcarbazepine; TOP, topiramate; PB, phenobarbital; LEV, levetiracetam; OXC, oxcarbazepine; SAB, vigabatrin; MRI, magnetic resonance imaging; iPTH, intact parathyroid hormone; vit, vitamin; CHD, congenital heart disease; NA, non-available. Bayley-III cognitive scores were interpreted as: normal, ≥ 85 points; mild, ≥ 70 and < 85 points; moderate, ≥ 55 and < 70 points; and severe, < 55 points (14, 15). NA, non-available. The sequence data of ALMS1 reference sequence NM_015120.4.