Case#: Patient 2, Turkish, 4 years old (report)

DiseaseAssertion: Accumulation of guanidinoacetate in brain and a deficiency of creatine in blood. GAMT deficiency in the liver.

FamilyInfo:

CasePresentingHPOs: HP:0011344, HP:0001252, HP:0001251 (Severe developmental delay, muscular hypotonia, ataxia)

CaseHPOFreeText: Intractable seizures, Bio- chemical and spectroscopy findings were similar to those of patient 1

CaseNotHPOs:

CaseNotHPOFreeText:

Biochemical analyte testing:

Brain Magnetic Resonance Spectroscopy (MRS):

GAMT activity assay: Total RNA from liver, fibroblasts, or leukocytes. The residual GAMT activity varied between levels below the limit of detection and 1.9 units/g liver. When 1:1 mixtures of liver extracts from the two patients and control livers were incubated, the GAMT activity exceeded the calculated activity by 40%-60%. This excludes the possibility that the deficiency of GAMT in the patients' livers is due to an inhibitor. It, rather, points to the presence of an activator of GAMT in the patients' livers. The activities of two unrelated enzymes (cytosolic lactate dehydrogenase and lysosomal ,B-hexosaminidase) and the protein content, which served as reference parameters, were within the same range of controls (table 1). Taken together, these results confirm the suspected deficiency of GAMT activity in the liver of the two patients.

Zygosity: Homozygous

Variant 1:

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CAID:

gnomAD:

Variant 2:

ClinVarID:

CAID:

gnomAD:

ParentalGenotypes:

PreviouslyPublished:

Case#: Patient 1, German, male, 22 months old (report)

DiseaseAssertion: Accumulation of guanidinoacetate in brain and a deficiency of creatine in blood. GAMT deficiency in the liver.

FamilyInfo:

CasePresentingHPOs: HP:0008947, HP:0007153, (Infantile muscular hypotonia, Progressive extrapyramidal movement disorder,

CaseHPOFreeText: emiballistic voluntary movements, at the age of 22 mo his developmental age was that of a 8-wk-old infant,

CaseNotHPOs:

CaseNotHPOFreeText:

Biochemical analyte testing:

Brain Magnetic Resonance Spectroscopy (MRS): Bilateral abnormal signal intensities in the globus pallidus. A severe deficiency of creatine and creatine phosphate and simultaneous accumulation of guanidinoactetate were detected by in vivo proton and phosphorous magnetic resonance spectroscopy of the brain.

GAMT activity assay: Total RNA from liver, fibroblasts, or leukocytes. The residual GAMT activity varied between levels below the limit of detection and 1.9 units/g liver. When 1:1 mixtures of liver extracts from the two patients and control livers were incubated, the GAMT activity exceeded the calculated activity by 40%-60%. This excludes the possibility that the deficiency of GAMT in the patients' livers is due to an inhibitor. It, rather, points to the presence of an activator of GAMT in the patients' livers. The activities of two unrelated enzymes (cytosolic lactate dehydrogenase and lysosomal ,B-hexosaminidase) and the protein content, which served as reference parameters, were within the same range of controls (table 1). Taken together, these results confirm the suspected deficiency of GAMT activity in the liver of the two patients.

Zygosity: Homozygous

Variant 1:

ClinVarID:

CAID:

gnomAD:

Variant 2:

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CAID:

gnomAD:

ParentalGenotypes:

PreviouslyPublished:

PMID: 8651275

Gene: GAMT

Disease: GAMT deficiency

Inheritance: Autosomal Recessive