GM28756

GM28756 LCL from B-Lymphocyte

Description:

CEREBRAL CREATINE DEFICIENCY SYNDROME 2; CCDS2
GUANIDINOACETATE METHYLTRANSFERASE; GAMT

Affected:

Yes

Sex:

Female

Age:

18 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
PIGI Consented Sample

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Subject Type

parent(s) and child(ren)

Ethnicity

Not Hispanic/Latino

Ethnicity

U.K.

Country of Origin

USA

Family Member

Family History

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected. Substantial developmental delay, moderate intellectual disability, and mild epilepsy. Patient 2 of Viau 2013 (PMID: 24071436). Patient 25 of Stockler-Ipsiroglu (PMID: 24268530). Assessed for developmental disabilities at 3 years of age. Seizures began at 5 years of age. Treatment began at 5 years and 6 months of age for 30 months; improvement on developmental delay, speech delay and behavior, remaining mild epilepsy. Brother GM28757 is currently asymptomatic after early diagnosis and treatment. Mother is GM28759. Father is GM28758. Fibroblast line is GM28379 and iPSC line is GM28936.

Characterizations

Gene

GAMT

Chromosomal Location

19p13.3

Allelic Variant 1

p.V78E; CEREBRAL CREATINE DEFICIENCY SYNDROME 2; CCDS2

Identified Mutation

c.233T>A

Gene

GAMT

Chromosomal Location

19p13.3

Allelic Variant 2

R105GfsX26; CEREBRAL CREATINE DEFICIENCY SYNDROME 2; CCDS2

Identified Mutation

c.299_c.311 dup13

Phenotypic Data

Demographic Data

Relation to Proband

proband

Age at Sampling

18 YR

Sex

Female

Age of Onset(If not a control)

1 YR

Age at Diagnosis(If not a control)

5 YR

Hispanic or Latino/Not Hispanic or Latino

Not Hispanic/Latino

Racial Category

White

Country

USA

Data Elements

Clinical Element Type: General NIGMS Catalog Remarks

(Baseline)

Mutation Information

Gene, variant, consequence, and exon number:

GAMT, C.299_C.311DUP13 (P.R105G1AX2B), EXON 2

Zygosity:

Compound Heterozygous

Other variants:

GAMT, C.233T>A (P. V78E), EXON 2

Age of Symptom Onset and Age at Diagnosis

Age of Symptom Onset:

1 YEAR

Age at Diagnosis:

5 YEARS

In Utero History Information

Birth History Information

Dysmorphic Features

Neurological Symptoms

Seizures

Additional Information:

SEIZURES BEGAN AGE 5 WITH ABSENCE EPILEPSY AND GENERALIZED TONIC-CLONIC EPISODES BEGINNING AT AGE 10.

Optical and Audiological Symptoms

Musculoskeletal Symptoms

Developmental Milestones

Delayed speech and language development
Global developmental delay

Additional Information:

ACADEMIC DELAYS

Gastrointestinal Symptoms

Genitourinary Symptoms

Respiratory and Cardiovascular Symptoms

Cognitive and Behavioral Symptoms

Behavioral problems
Learning disability

Intellectual Disability:

Moderate

Additional Information:

CLINICALLY PROBLEMS WITH INHIBITION, EMOTIONAL CONTROL, PLANNING/ORGANIZATION, SELF-MONITORING, ATYPICALITY, WITHDRAWAL, AND FUNCTIONAL COMMUNICATIONS. DEFICITS IN ADAPTIVE FUNCTIONING AND DAILY FUNCTIONING SKILLS; POSITIVE EMOTIONAL AND BEHAVIORAL ADJUSTMENT.

Additional Information

Uncategorized Symptoms:

EUTHYMIC MOOD AND ALERT; SIGNIFICANT COGNITIVE SLOWING; LIMITED RECEPTIVE AND EXPRESSIVE LANGUAGE SKILLS WITH LIMITED VOCABULARY DEVELOPMENT; ARTICULATE AND INTELLIGIBLE SPEECH.

Testing Performed

Cognitive and Behavioral Testing:

WECHSLER INTELLIGENCE SCALE FOR CHILDREN; BEHAVIOR ASSESSMENT SYSTEM FOR CHILDREN; BEHAVIOR RATING INVENTORY OF EXECUTIVE FUNCTION (BRIEF). VERBAL COMPREHENSION (45) EXTREMELY LOW; VISUAL SPATIAL (45) EXTREMELY LOW; FLUID REASONING (61) EXTREMELY LOW; WORKING MEMORY (59) EXTREMELY LOW; PROCESSING SPEED (56) EXTREMELY LOW.

Treatments and Assistive Devices

Speech therapy
Communication or learning devices

Surgeries

LITHOTRIPSY, VAGAL NERVE STIMULATION, TOTAL SHOULDER ARTHROPASTY.

Medications

LAMICTAL, ONFI.

Family History

YOUNGER BROTHER IS CURRENTLY ASYMPTOMATIC DUE TO EARLY DIAGNOSIS AND TREATMENT.

Remarks

Publications

Stockler-Ipsiroglu S, van Karnebeek C, Longo N, Korenke GC, Mercimek-Mahmutoglu S, Marquart I, Barshop B, Grolik C, Schlune A, Angle B, Araújo HC, Coskun T, Diogo L, Geraghty M, Haliloglu G, Konstantopoulou V, Leuzzi V, Levtova A, Mackenzie J, Maranda B, Mhanni AA, Mitchell G, Morris A, Newlove T, Renaud D, Scaglia F, Valayannopoulos V, van Spronsen FJ, Verbruggen KT, Yuskiv N, Nyhan W, Schulze A, Guanidinoacetate methyltransferase (GAMT) deficiency: outcomes in 48 individuals and recommendations for diagnosis, treatment and monitoring Molecular genetics and metabolism111:16-25 2013

PubMed ID: 24268530

Viau KS, Ernst SL, Pasquali M, Botto LD, Hedlund G, Longo N, Evidence-based treatment of guanidinoacetate methyltransferase (GAMT) deficiency Molecular genetics and metabolism110:255-62 2013

PubMed ID: 24071436