Case#: Family 2: Patient B, a 10 y/o girl of Indian origin

DiseaseAssertion: Guanidinoacetate methyltransferase deficiency. Pathogenic homozygous missense variant in exon 5 of GAMT gene.

FamilyInfo: Born to nonconsanguineous parents. Uneventful birth history. Parents were confirmed to be carriers.

CasePresentingHPOs: HP:0002078, HP:0001249, HP:0040082, HP:0001263, HP:0001344, HP:0002474, HP:0002360, HP:0000752, HP:0000252

CaseHPOFreeText: Global developmental delay first was noted at 8–10 months of age when they had not achieved neck holding and social smile. They had no speech, poor expressive language, and cognition. They also had hyperactivity, sleep disturbances, frequent bursts of laughter, and happy predisposition. Reverse phenotyping with MRS brain confirmed an absent creatine peak in both siblings. The blood creatinine in patient B was 0.18 mg/dl (0.015 mmol/L), which is low.

CaseNotHPOs: HP:0032794, HP:0008542, HP:0000572, HP:0001999, HP:0031422

CaseNotHPOFreeText: No hearing or vision loss. On examination of both siblings, there was no dysmorphism. The cranial nerve assessment, tone, and deep tendon reflexes were normal. There were no abnormal cerebellar signs except for truncal ataxia. The MRI brain, EEG, and CMA were normal. The blood tandem mass spectrometry and urine GC-MS were normal. The methylation-specific PCR study for Angelman syndrome was normal.