CaseK1 Female, 12yr report, Bosnian

CasePresentingHPOs HP:0001557, HP:0025116, HP:0001941, HP:0002098, HP:0003270, HP:0002013, HP:0001290, HP:0000750, HP:0011344, HP:0002069, HP:0002305, HP:0001290, HP:0002059, HP:0004881

(Abnormal intrauterine movements, Fetal distress, Acidosis, Respiratory distress, Abdominal distension, Vomiting, Hypotonia, Speech delay, Severe GDD, Grand mal seizures, Athetosis, Hypotonia, Cerebral atrophy, Episodic hypoventilation)

HPOsFreeText born at 42wk gestation. (neonatal, pre-treatment:) apgar score at 1min:7, 5min:8, 10min:8, acidosis, respiratory distress, abdominal distension, vomiting, onset of fits at 2d, resistant to ACD's. (18mo:) introduced to pyridoxine therapy, trial dose/route of 60mg oral, complete cessation of seizures, no apnoea or hypotonia/sleepiness, initial maintenance dose of 800mg. (infancy/childhood:) recurrence of seizures with febrile illness, hypotonia, speech delay/difficulties, severe IQ delay. 1wk after withdrawal from pyridoxine trial at 7y, grand mal seizures recurred(definite PDE).

CaseNotHPOs HP:0000486

(Squint)

NotHPOsFreeText (infancy/childhood:) squint

CasePreviousTesting Administration of pyridoxine relieved patient's seizures. plasma pipecolic acid: 12(nv<2.5μM), plasma AASA: 1.5(nv<0.2μM), urine AASA: 7.5(nv<1 mmol/mol creatinine). Blood lactate: 5.4mM and CSF lactate: 4.4mM (nv <2.5mM). (PMID:17068770:)post treatment testing: Pipecolic acid in plasma 6.7(nv 0.7-2.6mmol/liter), AASA in plasma 0.9(nv<0.2mmol/liter), urine AASA 19(nv<1mmol/molcreatinine).

Variant NM_001182.4(ALDH7A1):c.328C>T (p.Arg110Ter), homozygous

ClinVar 17995

gnomAD MAF=0.0001385(Other), no homozygotes

CaseAddInfo parental consanguinity

CasePMIDs 10894227 (Patient 3...), 17068770 (Patient 8)

FamilyLabel Family S

FamilySPresentingHPOs HP:0002098, HP:0010818, HP:0002280

(Respiratory distress, Generalized tonic seizures, Mega cisterna magna)

HPOsFreeText (neonatal, pre-treatment:) respiratory distress, generalised tonic seizures. (infancy/childhood:) mega cisterna magna

FamilyNotHPOs n/a

CountryOrigin n/a

Ethnicity Arabic

Race n/a

FamilySPreviousTesting Cessation of seizures during pyridoxine therapy

ProbandLabel S1, Female, 15yr report

Variant NM_001182.4(ALDH7A1):c.312+2T>A, homozygous

ClinVar 17997

gnomAD not in gnomAD

FamilyAddInfo parental consanguinity

FamilyPMIDs n/a

CaseV1 Male, 6yr report, Dutch

CasePresentingHPOs HP:0025116, HP:0001941, HP:0002098, HP:0000737, HP:0010818, HP:0010851, HP:0000486, HP:0002464, HP:0001288, HP:0000750, HP:0000238, HP:0001263, HP:0100021

(Fetal distress, Acidosis, Respiratory distress, Irritability, Generalized tonic seizures, EEG with burst suppression, Squint, Spastic dysarthria, Gait difficulties, Speech delay, Hydrocephalus, Developmental delay, Cerebral palsy)

HPOsFreeText born at 35wk gestation. (neonatal, pre-treatment:) apgar score 1min:6, 5min:7; acidosis, respiratory distress, irritability, generalized tonic fits(onset at 1h old), burst suppression EEG, resistant to ACD's. (4do:) first pyridoxine trial, trial dose/route=50mg i/v, complete cessation of seizures, apnoea, hypotonia/sleepiness, hypotension, initial maintenance daily dose=50mg. (infancy/childhood:) squint, spastic dysarthria, gait problems, speech delay/difficulties, IQ:60-70, hydrocephalus on MRI requiring ventriculoperitoneal shunt. (PMID:16159904:) developmental delay, cerebral palsy

CaseNotHPOs HP:0001557, HP:0003270, HP:0002013, HP:0011169, HP:0001336, HP:0002521, HP:0025116

(Abnormal Intrauterine movements, Abdominal distension, Vomiting, Clonic seizures, Myoclonic jerk, Hypsarrhythmia, Fetal distress)

NotHPOsFreeText (neonatal, pre-treatment:) abdominal distension, clonic or myoclonic jerks, hypsarryhythmia, or other EEG changes. (infancy/childhood:) recurrence of seizures with febrile illness. (PMID:16159904:) intrauterine seizures, signs of fetal distress, for example, meconium stained amniotic fluid or abnormal cardiotocography

CasePreviousTesting Administration of pyridoxine relieved patient's seizures. CSF pipecolic acid: 6.9, 1.5(nv<0.15μM), plasma pipecolic acid: 5.3(nv<2.5μM), CSF AASA: 1(nv <0.1μM), plasma AASA: 2.4(nv<0.2μM), urine AASA: 12(nv<1 mmol/mol creatinine).

Variant 1. NM_001182.4(ALDH7A1):c.1279G>C (p.Glu427Gln), 2. NM_001182.4(ALDH7A1):c.328C>T (p.Arg110Ter), compound heterozygous

ClinVar 1. 17994, 2. 17995

gnomAD 1.MAF= 0.0006123(European(Non-Finnish)), no homozygotes, 2. MAF=0.0001385(Other), no homozygotes

CaseAddInfo nonconsanguineous parents

CasePMIDs 17721876, 17088338, 16159904

FamilyLabel Family H

FamilyHPresentingHPOs HP:0001557, HP:0001941, HP:0002098, HP:0003270, HP:0002013, HP:0001336, HP:0010851, HP:0000750

(Abnormal intrauterine movements, Acidosis, Respiratory distress, Abdominal distension, Vomiting, Myoclonic jerks, EEG with burst suppression, Speech delay)

HPOsFreeText born after 40wks gestation. (neonatal, pre-treatment:) apgar score at 1min:9, 5min:9, acidosis, respiratory distress, abdominal distension, vomiting, onset of myoclonic jerks at 12h, EEG burst suppression. (2d:) introduced to pyridoxine therapy, trial dose/route of 100mg i/v, complete cessation of seizures, ventilated, initial daily dose of 100mg. (infancy/childhood:) speech delay, IQ: 60-70, no seizures on withdrawal from therapy

FamilyNotHPOs n/a

CountryOrigin n/a

Ethnicity Turkish

Race n/a

FamilyHPreviousTesting Administration of pyridoxine relieved patient's seizures.

ProbandLabel H1

Variant NM_001182.4(ALDH7A1):c.518-1G>C, homozygous

ClinVar 17994

gnomAD MAF=0.0006123(European(non-Finnish)), no homozygotes

FamilyAddInfo 1st cousin parents

FamilyPMIDs n/a

CaseP1 Male, 4.5yr report, Austrian

CasePresentingHPOs HP:0010818, HP:0010851, HP:0001290, HP:0011343, HP:0007359, HP:0001942, HP:0002376, HP:0001290

(Generalized tonic seizures, EEG with burst suppression, Hypotonia, moderate GDD, focal seizures, Metabolic acidosis, Developmental regression, Hypotonia)

HPOsFreeText born 40wk gestation. (neonatal, pre-treatment) apgar scores at 1min:8, 5min:9, 10min: 10, generalized tonic fits at <1d old and burst suppression EEG. (3d:) introduced pyridoxine therapy, 100mg I/v trial dose/route, complete cessation of seizures, apnoea(3d), hypotonia, sleepiness, initial maintenance daily dose of 10 mg/kg. (infancy/childhood:) hypotonia, moderate IQ delay. (4d:) withdrew from pyridoxine trial then focal seizures recurrenced 3 weeks after(definite PDE). (PMID: 0894227) gestational toxicosis, birth weight 3,260g, myoclonic jerks of both arms with hours of birth.Paroxysms of polyspike-wave-activity on EEG, normal cranial imaging,CSF analysis

CaseNotHPOs n/a

CasePreviousTesting Administration of pyridoxine relieved patient's seizures. CSF pipecolic acid: 3.4(nv<0.15μM), urine AASA: 168 before treatment(nv<1 mmol/mol creatinine). Blood lactate: 4.0mM and CSF lactate: 4.2mM (nv <2.5mM). (PMID:17068770:)post treatment testing: Pipecolic acid in plasma 4.7(nv 0.7-2.6mmol/liter), AASA in plasma 2.6(nv<0.2mmol/liter), urine AASA 17(nv<1mmol/molcreatinine). (PMID: 0894227) CSF analysis, organic acids in urine, amino acids in serum, and VLCFAs were normal. Plasma PA at 1st week 49µmol/L(before treatment)(nv 1-3.2), at 1-6mo 14.3µmol/L, 6-12mo 10.1µmol/L, CSF PA at 0-1yr 3.38µmol/L.

Variant NM_001182.4(ALDH7A1):c.1279G>C (p.Glu427Gln), homozygous

ClinVar 17994

gnomAD MAF= 0.0006123(European(Non-Finnish)), no homozygotes

CaseAddInfo n/a

CasePMIDs 10894227 (Patient 2), 17068770 (Patient 11)

FamilyLabel Family C

FamilyCPresentingHPOs HP:0001941, HP:0002098, HP:0000737, HP:0011169, HP:0010818, HP:0001336, HP:0000750

(Acidosis, Respiratory distress, Irritability, Clonic seizures, Generalized tonic seizures, Myoclonic jerks, Speech delay)

HPOsFreeText (neonatal, pre-treatment:) acidosis, respiratory distress, irritability, clonic seizures, generalized tonic seizures, myoclonic jerks. no apnoea, hypotonia, sleepness, or hypotension during pyridoxine therapy. (infancy/childhood:) speech delay.

FamilyNotHPOs HP:0003270, HP:0002013, HP:0001290, HP:0010851, HP:0002521

(Abdominal distension, Vomiting, Hypotonia, EEG with burst suppression, Hypsarrhythmia)

NotHPOsFreeText (neonatal, pre-treatment:) abdominal distension, vomiting, hypotonia, EEG with burst suppression, hypsarrhythmia

CountryOrigin n/a

Ethnicity Turkish

Race n/a

FamilyCPreviousTesting n/a

ProbandLabel C1

Variant NM_001182.4(ALDH7A1):c.1597delG (p.Ala533Profs), homozygous

ClinVar 17999

gnomAD not in gnomAD

FamilyAddInfo 1st cousin parents

FamilyPMIDs n/a

FamilyLabel Family R

FamilyRPresentingHPOs HP:0000750

(Speech delay)

HPOsFreeText born at 40wks gestational age. (infancy/childhood:) motor problems, speech delay/difficulties

FamilyNotHPOs HP:0025116

(Fetal distress)

CountryOrigin n/a

Ethnicity Asian

Race n/a

FamilyRPreviousTesting n/a

ProbandLabel R1

Variant NM_001182.4(ALDH7A1):c.1224T>G (p.Tyr408Ter), homozygous

ClinVar 18000

gnomAD MAF=0.00006535(South Asian), no homozygotes

FamilyAddInfo first cousin parents

FamilyPMIDs n/a

CaseG1 Female, 17mo report, Turkish

CasePresentingHPOs HP:0003270, HP:0002013, HP:0000737, HP:0011169, HP:0010818, HP:0001336, HP:0011182

(Abdominal distension, Vomiting, Irritability, Clonic seizures, Generalized tonic seizures, Myoclonic jerks, Epileptiform EEG discharges)

HPOsFreeText born at 40wks gestation. (neonatal, pre-treatment:) abdominal distension, vomiting, irritability, 3wks onset of clonic and generalized tonic fits as well as myoclonic jerks, epileptiform discharges with normal background activity, resistance to ACD's. Pyridoxine trial introduced at 9wks, trial dose/route of 10mg/kg/d p.o., complete cessation of seizures, but experienced hypotonia/sleepiness, no apnoea or hypotension, initial maintenance daily dose=10mg/kg. Withdrew form trial at 7mo, seizures recurred after 17 days.

CaseNotHPOs HP:0001557, HP:0025116, HP:0001941, HP:0002098, HP:0001290, HP:0010851, HP:0002521, HP:0000486, HP:0000750

(Abnormal intrauterine movements, Fetal distress, Acidosis, Respiratory distress, Hypotonia, EEG with burst suppression, Hypsarrhythmia, Squint, Speech delay)

NotHPOsFreeText (neonatal, pre-treatment:) acidosis, respiratory distress, hypotonia, burst suppression on EEG, hypsarrythmia. (infancy/childhood:) recurrence of seizures with febrile illness, squint, motor problems, speech delay/difficulties, MRI changes

CasePreviousTesting Administration of pyridoxine relieved patient's seizures. CSF pipecolic acid: 0.6(nv<0.15μM), plasma pipecolic acid: 5.5, 4.9(nv<2.5μM), plasma AASA: 4.1(nv<0.2μM), urine AASA: 53(nv<1 mmol/mol creatinine).

Variant NM_001182.4(ALDH7A1):c.596C>T (p.Ala199Val), homozygous

ClinVar 17998

gnomAD not in gnomAD

CaseAddInfo 1st cousin parents

CasePMIDs n/a

Case4 sex unknown, Netherlands, Dutch

CasePresentingHPOs HP:0001250, HP:0002194

(Seizures, Delayed motor skills)

HPOsFreeText Seizures ceased upon administration of pyridoxine. (PMID:16159904:) 1st seizure at 8do, first administered pyridoxine(and age at trial) 2mo, initial dose:100mg, maintenance dose:100mg/day, mildly affected motor skills. (PMID:17088338:) Definite="recurrent (two or more) seizures of any type that cease within seven days of the administration of oral pyridoxine (usual dose, 30 mg/ kg/day; minimum dose, 15 mg/kg/day; maximum dose, 1000 mg/kg/day) or within 30 minutes of intravenous pyridoxine (usual dose, 100 mg; minimum dose, 50 mg), that recur when pyridoxine supplementation is withdrawn, and that cease again when pyridoxine is given as above"

CaseNotHPOs n/a

NotHPOsFreeText intrauterine seizures

CasePreviousTesting PDS confirmed metabolically: α‐AASA urine 4.0(nv <1mmol/mol cr), α‐AASA plasma 1.1(nv <0.2μmol/l), pipecolic acid urine 0.02(nv 0.55-24.1mmol/mol cr <6mo, 0.01–1.54mmol/mol cr >6 mo) pipecolic plasma 7.0(nv 3.75-10.8μmol/l <1wk, 0.7-2.46μmol/l >1wk)

Variant NM_001182.4(ALDH7A1):c.834G>A (p.Val278=)

ClinVar 18002

gnomAD not in gnomAD(C and not G at that position?)

CaseAddInfo Metabolic testing of sibling(Patient 6, heterozygous for the p.Val278= variant): α‐AASA urine 0.2(nv <1mmol/mol cr), α‐AASA plasma <0.2(nv <0.2μmol/l), pipecolic acid urine 0.02(nv 0.55-24.1mmol/mol cr <6mo, 0.01–1.54mmol/mol cr >6 mo) pipecolic plasma 2.2(nv 3.75-10.8μmol/l <1wk, 0.7-2.46μmol/l >1wk), but was not metabolically confirmed for PDS, development was also normal

CasePMIDs 17088338 , 16159904

Case2 unknown sex, Netherlands, Dutch

CasePresentingHPOs HP:0001250, HP:0001263

(Seizures, Developmental delay)

HPOsFreeText Seizures ceased upon administration of pyridoxine. (PMID:16159904:) 1st seizure at 4do, first administered pyridoxine 6mo, age at trial 1.7yr, initial dose:100mg, maintenance dose:100mg/day, delayed development(PMID:17088338:) Definite="recurrent (two or more) seizures of any type that cease within seven days of the administration of oral pyridoxine (usual dose, 30 mg/ kg/day; minimum dose, 15 mg/kg/day; maximum dose, 1000 mg/kg/day) or within 30 minutes of intravenous pyridoxine (usual dose, 100 mg; minimum dose, 50 mg), that recur when pyridoxine supplementation is withdrawn, and that cease again when pyridoxine is given as above"

CaseNotHPOs n/a

NotHPOsFreeText intrauterine seizures

CasePreviousTesting PDS confirmed metabolically: α‐AASA urine 4.7(nv <1mmol/mol cr), α‐AASA plasma 0.9(nv <0.2μmol/l), pipecolic acid urine 0.27(nv 0.55-24.1mmol/mol cr <6mo, 0.01–1.54mmol/mol cr >6 mo) pipecolic plasma 5.8(nv 3.75-10.8μmol/l <1wk, 0.7-2.46μmol/l >1wk)

Variant 1. NM_001202404.1:c.1321T>A (p.Cys441Ser), 2. NM_001182.4(ALDH7A1):c.834G>A (p.Val278=)

ClinVar 1. n/a, 2. 18002

CAID 1. CA360721136

gnomAD 1. not in gnomAD, 2. not in gnomAD(C and not G at that position?)

CaseAddInfo Parents heterozygous for either allele=variants in trans in the patient. Two unaffected siblings, one with neither variant and the other with one copy of the p.Cys441Ser variant

CasePMIDs 17088338 , 16159904

FamilyLabel Family 1

Family1PresentingHPOs HP:0001250

(Seizures)

HPOsFreeText Seizures ceased upon administration of pyridoxine. (PMID:16159904:)1st seizure at 2days old

FamilyNotHPOs n/a

NotHPOsFreeText intrauterine seizures

CountryOrigin Netherlands

Ethnicity Dutch

Race n/a

Family1PreviousTesting α‐AASA and pipecolic acid tested for in affect patients' plasma and urine.

ProbandLabel Case 1

Variant NM_001182.4(ALDH7A1):c.1279G>C (p.Glu427Gln) homozygous

ClinVar 17994

gnomAD MAF= 0.0006123(European(Non-Finnish)), no homozygotes

FamilyAddInfo n/a

FamilyPMIDs 17088338 , 16159904

FamilyLabel Family 2

Family2PresentingHPOs n/a

HPOsFreeText n/a

FamilyNotHPOs n/a

CountryOrigin Netherlands

Ethnicity Dutch

Race n/a

Family2PreviousTesting α‐AASA and pipecolic acid tested for in affect patients' plasma and urine.

ProbandLabel Case 12

Variant NM_001182.4(ALDH7A1):c.1279G>C (p.Glu427Gln) homozygous

ClinVar 17994

gnomAD MAF= 0.0006123(European(Non-Finnish)), no homozygotes

FamilyAddInfo n/a

FamilyPMIDs 17088338 , 16159904

FamilyLabel Family 3

Family3PresentingHPOs HP:0001250

(Seizures)

HPOsFreeText n/a

FamilyNotHPOs n/a

NotHPOsFreeText intrauterine seizures

CountryOrigin Netherlands

Ethnicity Dutch

Race n/a

Family3PreviousTesting α‐AASA and pipecolic acid tested for in affect patients' plasma and urine.

ProbandLabel 3

Variant NM_001182.4(ALDH7A1):c.1279G>C (p.Glu427Gln) homozygous

ClinVar 17994

gnomAD MAF= 0.0006123(European(Non-Finnish)), no homozygotes

FamilyAddInfo n/a

FamilyPMIDs 17088338 , 16159904

Case9 sex unknown, Netherlands, Dutch

CasePresentingHPOs HP:0001250, HP:0001263, HP:0000750

(Seizures, Psychomotor delay, Speech delay)

HPOsFreeText Seizures ceased upon administration of pyridoxine. (PMID:16159904:) 1st seizure at 3do, first administered pyridoxine(and age at trial) 8mo, initial dose:50mg, maintenance dose:50mg/day, psychomotor delay, poor language skills. (PMID:17088338:) Definite="recurrent (two or more) seizures of any type that cease within seven days of the administration of oral pyridoxine (usual dose, 30 mg/ kg/day; minimum dose, 15 mg/kg/day; maximum dose, 1000 mg/kg/day) or within 30 minutes of intravenous pyridoxine (usual dose, 100 mg; minimum dose, 50 mg), that recur when pyridoxine supplementation is withdrawn, and that cease again when pyridoxine is given as above"

CaseNotHPOs n/a

NotHPOsFreeText intrauterine seizures

CasePreviousTesting PDS confirmed metabolically: α‐AASA urine 9.6(nv <1mmol/mol cr), α‐AASA plasma 0.8(nv <0.2μmol/l), pipecolic acid urine 2.0(nv 0.55-24.1mmol/mol cr <6mo, 0.01–1.54mmol/mol cr >6 mo) pipecolic plasma 22(nv 3.75-10.8μmol/l <1wk, 0.7-2.46μmol/l >1wk)

Variant NM_001182.4(ALDH7A1):c.1279G>C (p.Glu427Gln) homozygous

ClinVar 17994

gnomAD MAF= 0.0006123(European(Non-Finnish)), no homozygotes

CaseAddInfo n/a

CasePMIDs 17088338 , 16159904

FamilyLabel Family 15

Family15PresentingHPOs HP:0001250

(Seizures)

HPOsFreeText seizure onset in neonatal period from minutes after birth until 3 weeks of age.

FamilyNotHPOs n/a

CountryOrigin Germany

Ethnicity n/a

Race Caucasian

Family15PreviousTesting Post treatment metabolic testing of plasma PA and AASA as well as urine AASA. Normal urine PA after pyridoxine treatment.

ProbandLabel Case 15

Case15previoustesting Pipecolic acid in plasma 7.0(nv 0.7-2.6µmol/liter), AASA in plasma 1.9(nv<0.2µmol/liter), urine AASA 16(nv<1mmol/molcreatinine).

Case15HPOsfreetext Probable PDE: either pyridoxine-responsive seizures and an affected sibling or neonatal seizures responsive to a single dose of pyridoxine with later recurrence of seizures again responsive to pyridoxine.

Case16

Case16previoustesting Pipecolic acid in plasma 9.1(nv 0.4-4.9µmol/liter), AASA in plasma 2.6(nv<0.2µmol/liter), urine AASA 10(nv<1mmol/molcreatinine).

Case16HPOsfreetext Definite PDE: formal pyridoxine withdrawal had resulted in reoccurrence of seizures that again responded to pyridoxine.

Variant NM_001182.4(ALDH7A1):c.1566-1G>T, homozygous

ClinVar 374140

gnomAD MAF= 0.00003529(European(non-Finnish)), no homozygotes

FamilyAddInfo n/a

FamilyPMIDs n/a

FamilyLabel Family 3

Family3PresentingHPOs HP:0001250

(Seizures)

HPOsFreeText seizure onset in neonatal period from minutes after birth until 3 weeks of age. Probable PDE: either pyridoxine-responsive seizures and an affected sibling or neonatal seizures responsive to a single dose of pyridoxine with later recurrence of seizures again responsive to pyridoxine.

FamilyNotHPOs n/a

CountryOrigin Turkey

Ethnicity n/a

Race Caucasian

Family3PreviousTesting Normal urine PA after pyridoxine treatment.

ProbandLabel Case 4

Case4PreviousTesting post-treatment: Pipecolic acid in plasma 31(nv 1-3.2µmol/liter). pre-treatment: CSF PA levels 4.6µmol/liter(nv 0.009–0.12), 2.3µmol/liter(nv<0.1)

Variant NM_001182.4:c.1373G>A (p.Ser458Asn), homozygous

ClinVar n/a

CAID CA360721594

gnomAD not in gnomAD

FamilyAddInfo consanguineous, Case 3 is the sibling of Case 4 with no metabolic testing, homozygous for the same variant, with probable PDE.

FamilyPMIDs n/a

for nucleotide coordinates add 84 or for codons add 28 to get the correct position on NM_001182.4 or just use the given coordinates on this old transcript NM_001201377.1

Case14 age/gender unknown, Caucasian, Bosnia

CasePresentingHPOs HP:0001250

(Seizures)

HPOsFreeText seizure onset in neonatal period from minutes after birth until 3 weeks of age. Definite PDE: formal pyridoxine withdrawal had resulted in reoccurrence of seizures that again responded to pyridoxine.

CaseNotHPOs n/a

CasePreviousTesting post treatment testing: Pipecolic acid in plasma 2.8(nv 0.7-2.6µmol/liter), AASA in plasma 0.5(nv<0.2µmol/liter), urine AASA 1.6(nv<1mmol/molcreatinine). Normal urine PA after pyridoxine treatment.

Variant 1. NM_001182.4:c.605G>T (p.Gly202Val ), 2. NM_001182.4:c.1184T>G (p.Val395Gly), compound heterozygous

ClinVar n/a

CAID 1. CA360731073, 2. CA360723766

gnomAD neither in gnomAD

CaseAddInfo n/a

CasePMIDs n/a

Case13 age/gender unknown, Caucasian, Germany

CasePresentingHPOs HP:0001250

(Seizures)

HPOsFreeText seizure onset in neonatal period from minutes after birth until 3 weeks of age. Possible PDE: no trial of pyridoxine withdrawal performed and no antecedent affected.

CaseNotHPOs n/a

CasePreviousTesting pre-treatment testing: Pipecolic acid in plasma 53(nv 1-3.2µmol/liter), PA in urine 410µmol/mmol creati-nine(nv 0.55–24.1), AASA in plasma 14(nv<0.2µmol/liter), urine AASA 342(nv<1mmol/molcreatinine).

Variant NM_001182.4(ALDH7A1):c.1279G>C (p.Glu427Gln), homozygous

ClinVar 17994

gnomAD not in gnomAD

CaseAddInfo n/a

CasePMIDs n/a

Case1 age/gender unknown, Caucasian, German

CasePresentingHPOs HP:0001250

(Seizures)

HPOsFreeText seizure onset in neonatal period from minutes after birth until 3 weeks of age. Possible PDE: no trial of pyridoxine withdrawal performed and no antecedent affected

CaseNotHPOs n/a

CasePreviousTesting post treatment testing: Pipecolic acid in plasma 16(nv 0.4-4.9µmol/liter), AASA in plasma 3.9(nv<0.2µmol/liter), urine AASA 62(nv<1mmol/molcreatinine). Normal urine PA after pyridoxine treatment.

Variant 1. NM_001182.4(ALDH7A1):c.902A>T (p.Asn301Ile), 2. NM_001182.4(ALDH7A1):c.1279G>C (p.Glu427Gln), compound heterozygous

ClinVar 1. 18001, 2. 17994

gnomAD neither in gnomAD

CaseAddInfo n/a

CasePMIDs n/a

Case12 age/gender unknown, Caucasian, Italy

CasePresentingHPOs HP:0001250

(Seizures)

HPOsFreeText seizure onset in neonatal period from minutes after birth until 3 weeks of age. Definite PDE: formal pyridoxine withdrawal had resulted in reoccurrence of seizures that again responded to pyridoxine.

CaseNotHPOs n/a

CasePreviousTesting post treatment testing: Pipecolic acid in plasma 5.4(nv 0.7-2.6µmol/liter), AASA in plasma 9.6(nv<0.2µmol/liter), urine AASA 24(nv<1mmol/molcreatinine). Normal urine PA after pyridoxine treatment.

Variant NM_001182.4:c.1003C>T (p.Arg335Ter), homozygous

ClinVar n/a

CAID CA126889823

gnomAD MAF= 0.0001307(South Asian), no homozygotes

CaseAddInfo n/a

CasePMIDs n/a

Case10 age/gender unknown, Caucasian, Germany

CasePresentingHPOs HP:0001250

(Seizures)

HPOsFreeText seizure onset in neonatal period from minutes after birth until 3 weeks of age. Probable PDE: either pyridoxine-responsive seizures and an affected sibling or neonatal seizures responsive to a single dose of pyridoxine with later recurrence of seizures again responsive to pyridoxine.

CaseNotHPOs n/a

CasePreviousTesting post treatment testing: Pipecolic acid in plasma 7.5(nv 0.4-4.9µmol/liter), AASA in plasma 5.5(nv<0.2µmol/liter), urine AASA 26(nv<1mmol/molcreatinine). Normal urine PA after pyridoxine treatment.

Variant NM_001182.4(ALDH7A1):c.1279G>C (p.Glu427Gln), homozygous

ClinVar 17994

gnomAD not in gnomAD

CaseAddInfo n/a

CasePMIDs n/a

Case9 age/gender unknown, Caucasian, Germany

CasePresentingHPOs HP:0001250

(Seizures)

HPOsFreeText seizure onset in neonatal period from minutes after birth until 3 weeks of age. Definite PDE: formal pyridoxine withdrawal had resulted in reoccurrence of seizures that again responded to pyridoxine.

CaseNotHPOs n/a

CasePreviousTesting post treatment testing: Pipecolic acid in plasma 5.5(nv 0.7-2.6µmol/liter), AASA in plasma 5.8(nv<0.2µmol/liter). Normal urine PA after pyridoxine treatment.

Variant 1. NM_001182.4:c.696-2A>G (p.=), 2. NM_001182.4(ALDH7A1):c.1279G>C (p.Glu427Gln), compound heterozygous

ClinVar 1. n/a 2. 17994

CAID 1. CA360730346

gnomAD neither in gnomAD

CaseAddInfo n/a

CasePMIDs n/a

Case6 age/gender unknown, Caucasian, Germany

CasePresentingHPOs HP:0001250

(Seizures)

HPOsFreeText seizure onset in neonatal period from minutes after birth until 3 weeks of age. Definite PDE: formal pyridoxine withdrawal had resulted in reoccurrence of seizures that again responded to pyridoxine.

CaseNotHPOs n/a

CasePreviousTesting post treatment testing: Pipecolic acid in plasma 23(nv 0.8-5.5µmol/liter), AASA in plasma 4.6(nv<0.2µmol/liter). Normal urine PA after pyridoxine treatment.

Variant 1. NM_001182.4(ALDH7A1):c.328C>T (p.Arg110Ter), 2. NM_001182.4(ALDH7A1):c.1279G>C (p.Glu427Gln), compound heterozygous

ClinVar 1. 17995 2. 17994

gnomAD 1. MAF=0.0001385(Other), no homozygotes 2. not in gnomAD

CaseAddInfo n/a

CasePMIDs n/a

Case5 age/gender unknown, Caucasian, Italy

CasePresentingHPOs HP:0001250

(Seizures)

HPOsFreeText seizure onset in neonatal period from minutes after birth until 3 weeks of age. Definite PDE: formal pyridoxine withdrawal had resulted in reoccurrence of seizures that again responded to pyridoxine.

CaseNotHPOs n/a

CasePreviousTesting post treatment testing: Pipecolic acid in plasma 7.8(nv 0.4-4.9µmol/liter), AASA in plasma 5.8(nv<0.2µmol/liter), urine AASA 28(nv<1mmol/molcreatinine). Normal urine PA after pyridoxine treatment.

Variant NM_001182.4(ALDH7A1):c.1279G>C (p.Glu427Gln), homozygous

ClinVar 17994

gnomAD not in gnomAD

CaseAddInfo n/a

CasePMIDs n/a