Case#: Index patient, 6 years old (age at report), caucasian, male

DiseaseAssertion: Creatine transporter deficiency

FamilyInfo: Mother and maternal grandmother have history of learning disabilities, severely retarded uncle, unnaffected aunt

CasePresentingHPOs: HP:0001290 , HP:0006863, HP:0000750, HP:0001256 (Hypotonia, severe expressive language delay, severe speech delay, mild mental retardation)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

Biochemical analyte testing: Increased creatine levels in urine and plasma

Brain Magnetic Resonance Spectroscopy (MRS): Brain proton MRS revealed an almost complete absence of the creatine signal.

Creatine uptake assay: Creatine uptake was measured in total cell lysates, creatine concentration of 25 μM uptake level was negligible, and creatine concentration of1 25 μM uptake level was negligible.

Variant: No varient ID directly identified. Hemizygous nonsense mutation, A 1539C→T transition in SLC6A8 (GenBank accession number NM_005629) resulted in the substitution of an arginine codon by a termination codon (R514→X).

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

Zygosity: Hemizygous

MaternalGenotype: grandmother aunt, and mother heterozygous for mutation

AdditionalParentalTesting: N/A

AlsoPublished: PMID: 11261517

Case#: V3, Pakistan, female, 23 years old (report),

DiseaseAssertion: GAMT deficiency

FamilyInfo: Patient V3 is a sister of V1. Consanguineous family.

CasePresentingHPOs: HP:0010864, HP:0001250, HP:0001257, HP:0003487, HP:0001251, HP:0001761 (severe intellectual disability, seizure, spasticity, Babinski sign, ataxia, pes cavus)

CaseHPOFreeText: Neonatal onset of seizures, Spasticity in upper and lower limbs, Peripheral neuropathy probably present, sitting delayed, standing delayed, walking delayed, never developed speech

CaseNotHPOs: HP:0001347 (hyperreflexia)

CaseNotHPOFreeText: Bed ridden, recurrent bone fractures

Biochemical analyte testing:

Brain Magnetic Resonance Spectroscopy (MRS): N/A

GAMT activity assay: N/A

Zygosity: Homozygous / compound heterozygous.

Variant 1: c.134G > A (p.Trp45)

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

Variant 2: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

ParentalGenotypes: Both parents confirmed to be heterozygous for c.134G > A

AlsoPublished: N/A

Case#: V1, Pakistan, male, 25 years old (report),

DiseaseAssertion: GAMT deficiency

FamilyInfo: Patient V1 is a brother of V3. Consanguineous family.

CasePresentingHPOs: HP:0010864, HP:0001250, HP:0001347, HP:0001257, HP:0003487, HP:0001251, HP:0001761 (severe intellectual disability, seizure, hyperreflexia, spasticity, Babinski sign, ataxia, pes cavus)

CaseHPOFreeText: Neonatal onset of seizures, Spasticity in upper and lower limbs, Peripheral neuropathy probably present, sitting delayed, standing delayed, walking delayed, never developed speech, bed ridden since age 17, recurrent bone fractures

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

Biochemical analyte testing: GAA: 13.7 μmol/L, creatine: 2 μmol/L

Brain Magnetic Resonance Spectroscopy (MRS): N/A

GAMT activity assay: N/A

Zygosity: Homozygous

Variant 1: c.134G > A (p.Trp45)

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

Variant 2: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

ParentalGenotypes: Both parents confirmed to be heterozygous for c.134G > A

AlsoPublished: N/A