| Demographic Data |
| Relation to Proband |
proband |
| Age at Sampling |
3 YR |
| Sex |
Male |
| Age of Onset(If not a control) |
21 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: |
GENOME SEQUENCING REVEALED A HETEROZYGOUS, PATHOGENIC VARIANT (C.3518 C>T) IN THE MTR GENE RESULTING IN A MISSENSE MUTATION (P.PRO1173LEU). FUNCTIONAL STUDIES OF METHIONINE SYNTHASE ACTIVITY IN FIBROBLAST CELL LINE FROM A PATIENT CARRYING THIS VARIANT SHOWED A 30-FOLD REDUCTION IN ENZYMATIC ACTIVITY RELATIVE TO CONTROLS. IT IS PREDICTED BY MULTIPLE IN SILICO TOOLS TO HAVE A DELETERIOUS EFFECT ON PROTEIN FUNCTION. |
| Zygosity: |
Compound Heterozygous |
| Other variants: |
GENOMIC SEQUENCING REVEALED A LIKELY PATHOGENIC, HETEROZYGOUS INTRAGENIC 3.5KB DELETION, CHR1:237054424-237057937X1 (DEL(1Q43)) IN THE MTR GENE. THIS DELETION ENCOMPASSES EXONS 29 AND 30 AND IS PREDICTED TO BE A LOSS OF FUNCTION VARIANT. |
| Age of Symptom Onset and Age at Diagnosis |
| Age of Symptom Onset: |
21 MONTHS |
| Age at Diagnosis: |
NEWBORN |
| In Utero History Information |
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| Birth History Information |
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| Dysmorphic Features |
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| Additional Information: |
RASH AND NON SPECIFIC SKIN ERUPTION |
| Neurological Symptoms |
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| Additional Information: |
PERIODIC LIMB MOVEMENT DISORDER; MULTIPLE MRI'S FOR MONITORING COBALAMIN G SHOWED BORDERLINE SMALL CALIBER OF OPTIC NERVES, CHIASM, AND TRACTS WHICH HAS BEEN UNCHANGED SINCE BASELINE MRI, OTHERWISE NORMAL MRI |
| Optical and Audiological Symptoms |
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| Additional Information: |
VISUAL DISCOMFORT |
| Musculoskeletal Symptoms |
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| Developmental Milestones |
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| Gastrointestinal Symptoms |
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Constipation
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| Genitourinary Symptoms |
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| Respiratory and Cardiovascular Symptoms |
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| Additional Information: |
UPPER AIRWAY RESISTANCE SYNDROME |
| Cognitive and Behavioral Symptoms |
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| Additional Information |
| Uncategorized Symptoms: |
HIGH LEVELS OF FAT IN BLOOD; HIGH LEVELS OF HOMOCYSTEINE; AMINO ACID TESTS SHOWED SLIGHT DEVIATIONS FROM MOST AMINO ACIDS WITHOUT CLINICAL CONSEQUENCE, KNOWN TO HAVE METHIONINE SYNTHASE DEFICIENCY |
| Testing Performed |
| Neurological Testing: |
EEG; SLEEP STUDY; MRI: MOSTLY NORMAL |
| Metabolic, Hematologic, and Endocrinologic Testing: |
HOMOCYSTEINE: 45.2 (H)
METHIONINE: 44
GLUTAMIC ACID 308 (H) |
| Treatments and Assistive Devices |
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Occupational therapy
Speech therapy
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| Medications |
| |
BETAINE; FOLIC ACID; METHIONINE; SINGULAIR; HYDROXOCOBALAMIN; LEUCOVORIN; LIDOCAINE-PRILOCAINE; INSULIN; FLUTICASONE PROPIONATE |
| Family History |
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OLDER BROTHER IS ALSO AFFECTED |
| Remarks |
Clinically affected. See "Phenotypic Data" tab; metabolic disease diagnosed by newborn screen; visual discomfort developed at 21 months of age; compound heterozygous mutation in the MTR gene: c.3518C>T (p.Pro1173Leu) and 3 3.5-Kb deletion spanning exons 29 and 30; also a heterozygous mutation in the LMBRD1 gene c.1056del (p.Asn353Ilefs); unaffected mother is GM28743 (lymph) and unaffected father is GM28742 (lymph). One affected brother. |