| Demographic Data |
| Relation to Proband |
proband |
| Age at Sampling |
18 YR |
| Sex |
Female |
| Age of Onset(If not a control) |
4 MO |
| Age at Diagnosis(If not a control) |
16 MO |
| Hispanic or Latino/Not Hispanic or Latino |
Not Hispanic/Latino |
| Racial Category |
Asian |
| Country |
USA |
| |
| Data Elements |
| Clinical Element Type: General NIGMS Catalog Remarks |
| (Baseline) |
| Mutation Information |
| Gene, variant, consequence, and exon number: |
HOMOZYGOUS MUTATION IN THE DONOR SPLICE SITE OF EXON 3 OF GATM: IVS3+1G>T (C.484+1G>T; W194X) RESULTING IN SKIPPING OF EXON 3 (R.289_484DEL196) |
| Zygosity: |
Homozygous |
| Age of Symptom Onset and Age at Diagnosis |
| Age of Symptom Onset: |
4 MONTHS |
| Age at Diagnosis: |
16 MONTHS; DIAGNOSED BY A GENETICIST |
| In Utero History Information |
| |
|
| Additional Information: |
BORN AT TERM; UNEVENTFUL PREGNANCY |
| Birth History Information |
| |
Failure to thrive
|
| Additional Information: |
AT 4 MONTHS, FAILURE TO THRIVE HAD RESOLVED AND CURRENTLY PHENOTYPE IS NORMAL |
| Dysmorphic Features |
| |
|
| Additional Information: |
AT 12 YEARS: SHORT STATURE, DELAYED GROWTH AND PUBERTY |
| Neurological Symptoms |
| |
Hypotonia
|
| Optical and Audiological Symptoms |
| |
Defective vision
|
| Additional Information: |
MYOPIA |
| Musculoskeletal Symptoms |
| |
|
| Developmental Milestones |
| |
Delayed speech and language development
|
| Additional Information: |
MILD TO MODERATE GLOBAL DEVELOPMENTAL DELAY; POOR WEIGHT GAIN AT 10 MONTHS; AT 3 YEARS DELAY IN COMPREHENSIVE AND EXPRESSIVE LANGUAGE SKILLS; AT 13 YEARS SPEECH PROCESSING DISORDER; AT 19 YEARS EXCELS ACADEMICALLY, NO PHYSICAL LIMITATIONS, NORMAL SPEECH |
| Gastrointestinal Symptoms |
| |
|
| Genitourinary Symptoms |
| |
|
| Respiratory and Cardiovascular Symptoms |
| |
|
| Cognitive and Behavioral Symptoms |
| |
|
| Additional Information |
| Testing Performed |
| Neurological Testing: |
AT 2 YEARS, MRI: NORMAL; AT 2 AND 11 YEARS, MRS: CREATINE TO NAA RATIO 50-60% OF NORMAL WITHIN THALAMUS AND BASAL GANGLIA WITH MILDLY DECREASED RATIO COMPARED TO AGE-MATCHED CONTROLS |
| Metabolic, Hematologic, and Endocrinologic Testing: |
INBORN ERROR OF METABOLISM; AT 10 MONTHS, URINE AMINO ACIDS NORMAL, EXTREMELY LOW LEVELS OF URINE AND PLASMA GUANIDINOACETATE (PLASMA 0.07 UMOL/L) AND PLASMA CREATINE (2.3 UMOL/L); AT 2 YEARS, GENERALIZED ORGANIC ACIDURIA (ORGANIC ACID CONCENTRATIONS RANGED 2-5X THE UPPER LIMITS OF NORMAL), LOW CREATINE, GATM LEVEL NOT DETECTABLE; NORMAL RENAL ULTRASOUNDS; AT 12 YEARS, BUN, CREATINE, AND ELECTROLYTES NORMAL EXCEPT FOR SLIGHTLY LOW CO2 OF 23; 1H-MRS AT 2 YEARS SHOWED COMPLETE ABSENCE OF CREATINE PEAK, AND SEQUENTIAL BRAIN MRS REVEALED RECOVERY OF CEREBRAL CREATINE LEVEL TO 80-90% OF NORMAL AFTER 23 MONTHS OF ORAL CREATINE SUPPLEMENTATION; AT 2 YEARS GATM ACTIVITY NOT DETECTABLE, ARGININE GLYCINE AMIDINOTRANSFERASE ACTIVITY NOT DETECTABLE |
| Uncategorized Testing: |
NORMAL KARYOTYPE: 46,XX; NORMAL KIDNEY FUNCTION TESTS |
| Treatments and Assistive Devices |
| |
Occupational therapy
|
| Additional Testing: |
SPEECH THERAPY AT 27 MONTHS TO 9 YEARS OF AGE |
| Medications |
| |
CREATINE 200-800 MG/KG/D, CURRENTLY ~515 MG/KG/D |
| Family History |
| |
THE DONORS PARENTS (NOT IN REPOSITORY) ARE HETEROZYGOUS FOR THE MUTATION IN GATM: IVS3+1G>T. |
| Remarks |
See Phenotypic Data tab. Same subject as GM27955. Researchers purchasing hiPSCs from the NIGMS Repository are responsible for any limited use label licenses (LULLs) applicable to the cell line purchased. The applicable LULL to this line is Sendai-CytoTune. |