GM28071

GM28071 LCL from B-Lymphocyte

Description:

CEREBRAL CREATINE DEFICIENCY SYNDROME 2; CCDS2
GUANIDINOACETATE METHYLTRANSFERASE; GAMT

Affected:

Yes

Sex:

Female

Age:

12 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

concordant sib pair

Ethnicity

Not Hispanic/Latino

Ethnicity

German

Country of Origin

USA

Family Member

Family History

Relation to Proband

sibling

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected. See Phenotypic Data Tab. Patient #4 in Stockler-Ipsiroglu, et al. 2014 (PMID:24268530). Failure to thrive and developmental delay before treatment at 9 months. After 21 months treatment, still had developmental and speech delays. Affected sibling is GM28070 (LCL) and GM28096 (fibroblast).

Characterizations

Gene

GAMT

Chromosomal Location

19p13.3

Allelic Variant 1

601240.0001; CEREBRAL CREATINE DEFICIENCY SYNDROME 2; CCDS2

Identified Mutation

c.327G>A (p.K109K, splice site mutation)

Gene

GAMT

Chromosomal Location

19p13.3

Allelic Variant 2

601240.0007; CEREBRAL CREATINE DEFICIENCY SYNDROME 2; CCDS2

Identified Mutation

c.522G>A (P.W174X)

Phenotypic Data

Demographic Data

Relation to Proband

sibling

Age at Sampling

12 YR

Sex

Female

Age of Onset(If not a control)

6 MO

Age at Diagnosis(If not a control)

13 MO

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.327G>A, SPLICING, EXON 2

Zygosity:

Heterozygous

Other variants:

GAMT, C.522G>A (P.W174X), NONSENSE, EXON 5, HETEROZYGOUS, INFERRED FROM THE BROTHER

Age of Symptom Onset and Age at Diagnosis

Age of Symptom Onset:

4 MONTHS

Age at Diagnosis:

13 MONTHS

In Utero History Information

Birth History Information

Failure to thrive

Additional Information:

WEIGHT AT 0.11% GROWTH PERCENTILE AT 12 MONTHS

Dysmorphic Features

Neurological Symptoms

Optical and Audiological Symptoms

Musculoskeletal Symptoms

Developmental Milestones

Delayed speech and language development
Global developmental delay
Abnormal weight for age

Additional Information:

STARTED SITTING INDEPENDENTLY AT 8 MONTHS DID NOT HAVE RECOGNIZABLE WORDS AT 12 MONTHS

Gastrointestinal Symptoms

Genitourinary Symptoms

Respiratory and Cardiovascular Symptoms

Cognitive and Behavioral Symptoms

Additional Information

Testing Performed

Metabolic, Hematologic, and Endocrinologic Testing:

PLASMA CREATINE AT 1 YEAR: 2.6 MICROMOLE/L (LOW) PLASMA GUANIDINOACETATE AT 1 YEAR: 19.6 MICROMOLE/L (HIGH)

Treatments and Assistive Devices

Physical therapy

Surgeries

G-TUBE PLACEMENT

Medications

CREATINE, ORNITHINE-HIGH DOSE, DIET LOW PROTEIN RESTRICTION, ARGININE-RESTRICTED DIET, SODIUM BENZOATE

Family History

OLDER BROTHER IS ALSO AFFECTED

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