Case#: Patient (case report), male, 1 month old, ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: No history of consanguinity in parents. The patient has a 15 months old sibling that is healthy.

Family medical history was notable for tuberous sclerosis in the patient’s father’s first cousin.

CasePresentingHPOs: HP:0200128, HP:0001639, HP:0002240

(Biventricular hypertrophy, Hypertrophic cardiomyopathy, Hepatomegaly,

CaseHPOFreeText: Echogenic mass within the left ventricle.

Short-axis images revealed the possibility of an additional mass within the left ventricle adjacent to the papillary muscles

Right axis deviation

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

Normal results were noted for levels of plasma amino acids, lactate and pyruvate, total and free carnitine, and acylcarnitine compounds. Urine organic acid quantitation was normal.

PR interval was normal

CasePreviousTesting: The serum creatine kinase was elevated (478 U/L; normal 60–305 U/L).

GAA activity in whole blood from a blood spot was 1.8 pmol/punch/hour (control 10–49 pmol/punch/hour)

The GAA gene was sequenced.

Variant 1: NM_000152.5(GAA):c.525del (p.Glu176fs)

ClinVar: 4033

CAID: CA220406

gnomAD: N/A

Variant 2: NM_000152.5(GAA):c.1927G>A (p.Gly643Arg)

ClinVar: 4023

CAID: CA116596

gnomAD: Highest population MAF=0.00003667 (Euroean (non-Finnish))

ParentalGenotype:N/A

PreviouslyPublished:N/A

Case#: Patient 7, Gender N/A, Onset 3-4 months. Death around 1-2 years, Southeast Asian

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: P:0001639. HP:0005165, HP:0001270, HP:0002240

(Dyspnea, Shortened PR interval, Motor delay, Hepatomegaly

CaseHPOFreeText: BVH, Severe MR, SDD, CK 550u/l, EF

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: Creatine Kinase enzyme 550u/l, Ejection fraction 30%, GAA enzyme activity in leukocytes was 0.05% of normal control value.

PCR of all exons was performed and subsequently subjected to capillary Sanger sequencing in both directions

Variant 1: NM_000152.5(GAA):c.1411_1414del (p.Glu471fs)

ClinVar: 188874

CAID: CA274067

gnomAD: Highest population MAF = 0.0002513 in East Asian

Variant 2: NM_000152.5(GAA):c.1933G>C (p.Asp645His)

ClinVar: 189013

CAID: CA274256

gnomAD: Highest population MAF = 0.00005534 (East Asian)

ParentalGenotype: Father was the carrier of variant 1 NM_000152.5(GAA):c.1411_1414del (p.Glu471fs)

mother was carrier of variant 2 NM_000152.5(GAA):c.1933G>C (p.Asp645His)

PreviouslyPublished: N/A

Case#: Patient 1, gender N/A, Age of onset was 7-8 months (died at 3 years of age), Southeast Asian

DiseaseAssertion: Pompe Disease

FamilyInfo:

CasePresentingHPOs: HP:0001252, HP:0001270, HP:0001638, HP:0005165 (Muscular Hypotonia, Motor delay, Cardiomyopathy, Shortened PR interval)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: GAA activity in leukocytes was 0% of the normal control value.

PCR of all exons was performed and subsequently subjected to capillary Sanger sequencing in both directions

Variant1: NM_000152.5(GAA):c.876C>G (p.Tyr292Ter)

ClinVar: 637958

CAID: CA401363871

gnomAD: N/A

Variant2: NM_000152.5:c.1003G>A (p.Gly335Arg)

ClinVar: 972790

CAID: CA501005

gnomAD: Highest population MAF = 0.00003266 (South Asian).

ParentalGenotype: Patient inherited variant 1 (NM_000152.5(GAA):c.876C>G (p.Tyr292Ter) from father.

Variant 2 (c.1003G>A (p.Gly335Arg)) was inherited from mother PreviouslyPublished:N/A

Case#: Patient 4, Gender N/A, onset at 3-4 months. Died at 9 months, Southeast Asian

DiseaseAssertion:Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002094 HP:0001639. HP:0005165, HP:0001270 (Hypertrophic Cardiomyopathy, Dyspnea, Shortened PR interval, Motor delay )

CaseHPOFreeText: BVH, Died from dehydration (diarrhea)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: GAA activity in leukocytes was 0% of normal control value.

PCR of all exons was performed and subsequently subjected to capillary Sanger sequencing in both directions

Variant 1: c.1225dup (p.Asp409GlyfsX95)

ClinVar: N/A

CAID: CA923726362

gnomAD: N/A

Variant 2: c.2024_2026delACA (p.Asn675del)

ClinVar: 189006

CAID: CA274244

gnomAD: Highest population MAF = 0.0001106 (East asians)

ParentalGenotype: Father was carrier for Variant1 c.1226insG (p.Asp409GlyfsX95)

Mother was carrier of Variant 2 c.2024_2026delACA (p.Asn675del)

PreviouslyPublished: N/A

Case#: Patient 5, Gender N/A, Onset at 5-6 months. Death at 1.5 years of age, Southeast Asian

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002094 HP:0001639. HP:0005165, HP:0001270, HP:0001252, HP:0001714, HP:0002090

(Hypertrophic Cardiomyopathy, Dyspnea, Shortened PR interval, Motor delay, Muscular hypotonia, Ventricular hypertrophy, Pneumonia )

CaseHPOFreeText: Death from heart failure and pneumonia

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: GAA activity in leukocytes was 0% of normal control value.

PCR of all exons was performed and subsequently subjected to capillary Sanger sequencing in both directions

Variant 1: NM_000152.5(GAA):c.1538A>G (p.Asp513Gly)

ClinVar: 638014

CAID: CA401367134

gnomAD: N/A

ParentalGenotype: Both parents carried the .1538A>G (p.Asp513Gly) variant in the GAA gene. There was no parental consanguinity

PreviouslyPublished: N/A

Case#: Patient 8, Gender N/A, Onset at 1-2 months. Death at 13 months. Southeast Asian

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002240, HP:0001252, HP:0002789, HP:0001698 (Hepatomegaly, Muscular hypotonia, Tachypnea, Pericardial effusion)

CaseHPOFreeText: Hepatomegaly is mild, Pericardial effusion is mild, BHV, SDD

CaseNotHPOs: N/A

CaseNotHPOFreeText: Normal PR Interval

CasePreviousTesting: GAA activity in leukocytes was 1.46% of normal control value.

PCR of all exons was performed and subsequently subjected to capillary Sanger sequencing in both directions

Variant: NM_000152.5(GAA):c.877G>A (p.Gly293Arg)

ClinVar: 4036

CAID: CA116622

gnomAD: Highest population MAF = 0.00005704 (Latino)

ParentalGenotype: Both parents were carriers of the variant c.877G>A (p.Gly293Arg)

PreviouslyPublished: N/A

Case#: Patient 6, Gender N/A, Onset at 5-6 months. Death around 2 years old, Southeast Asian

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: P:0001639. HP:0005165, HP:0001270, HP:0011968

(Dyspnea, Shortened PR interval, Motor delay, Feeding difficulties,

CaseHPOFreeText: FTT, BVH, Severe MR)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: GAA activity in leukocytes was 0.43% of normal control value.

PCR of all exons was performed and subsequently subjected to capillary Sanger sequencing in both directions

Variant: NM_000152.5(GAA):c.781G>A (p.Ala261Thr)

ClinVar: 456438

CAID: CA8815016

gnomAD: Highest population MAF = 0.00009799 (South Asian)

ParentalGenotype: Father and Mother were carriers of the variant c.781G>A (p.Ala261Thr)

PreviouslyPublished: N/A

Case#: Patient 1, Gender N/A, age N/A, ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001638, HP:0003756

(Cardiomyopathy, Skeletal myopathy)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Sequence analysis of the GAA gene was performed in a CLIA and CAP certified laboratory.

Cross Reactive Immune reaction was indeterminate in peripheral blood mononuclear cells (PBMCs)

Cross Reactive Immune reaction was negative in Dried blood spots.

Variant 1: c.437delT (p.Met146ArgfsX7)

ClinVar: N/A

CAID: N/A

gnomAD: N/A

Variant 2: NM_000152.5(GAA):c.2237G>A (p.Trp746Ter)

ClinVar: 280063

CAID: CA8815664

gnomAD: Two variants with same consequence (protein) were identified.

Highest population MAF = 0.00004011 (African)

Highest population MAF = 0.000008834 (European non-Finnish)

ParentalGenotype: N/A

Previously published: N/A

Case#: Patient 3, Gender unknown, age unknown, ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001638, HP:0003756

(Cardiomyopathy, Skeletal myopathy)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Sequence analysis of the GAA gene was performed in a CLIA and CAP certified laboratory. Cross Reactive Immune reaction was indeterminate in peripheral blood mononuclear cells (PBMCs)

Cross Reactive Immune reaction was negative in Dried blood spots.

Variant: NM_000152.5(GAA):c.2560C>T (p.Arg854Ter)Cite this record

ClinVar: 4034

CAID: CA340130

gnomAD: Highest population MAF= 0.001891 (African)

ParentalGenotype: N/A

PreviouslyPublished:N/A

Case#: Patient 4, Gender unknown, age unknown, ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001638, HP:0003756

(Cardiomyopathy, Skeletal myopathy)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Sequence analysis of the GAA gene was performed in a CLIA and CAP certified laboratory. Cross Reactive Immune reaction was indeterminate in peripheral blood mononuclear cells (PBMCs)

Cross Reactive Immune reaction was not available in Dried blood spots.

Variant: NM_000152.5(GAA):c.2560C>T (p.Arg854Ter)

ClinVar: 4034

CAID:CA340130

gnomAD: Highest population MAF= 0.001891 (African)

ParentalGenotype: N/A

Case#: Patient 6, gender unknown, age unknown, ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001638, HP:0003756

(Cardiomyopathy, Skeletal myopathy)

CaseHPOFreeText:N/A

CaseNotHPOs: N.A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Sequence analysis of the GAA gene was performed in a CLIA and CAP certified laboratory.

Cross Reactive Immune reaction was negative in peripheral blood mononuclear cells (PBMCs)

Cross Reactive Immune reaction was not available in Dried blood spots.

Variant: NM_000152.5(GAA):c.2297A>C (p.Tyr766Ser)

ClinVar: 420102

CAID: CA8815680

gnomAD: Highest population MAF= 0.00005441 (East asian)

ParentalGenotype: N/A

PreviouslyPublished:N/A

Case#: LOPD patient #1, Male, 69, ethnicity unknown.

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002094, HP:0006554, HP:0012378, HP:0001324 (Dyspnea, Acute respiratory failure, Fatigue, Lower Girdle Muscle Weakness and Upper Girdle Muscle Weakness)

CaseHPOFreeText: Dyspnea was present during exercise, not at rest. Lower Girdle Muscle Weakness and Upper Girdle Muscle Weakness share the same HPO.

CaseNotHPOs:

CaseNotHPOFreeText: Patient has normal creatine phosphokinase levels, No Dyspnea at rest, No Ortopnea, No Airways infections, no myalgia

CasePreviousTesting: GAA gene sequencing to asses genotype.

GAA activity was reduced (0.36 microMol/L/h) in reference to standard (10.1 ± 6.6 microMol/L/h) This was measured by dried blood spot .

GAA muscle activity was 3.6 pmol/min/mg, no reference range was provided

Variant: Variant 1: NM_000152.5:c.-32-13T>G

ClinVar: 4027

CAID: CA116606

gnomAD: MAF= 0.005541 (Ashkenazi Jewish)

Variant 2: NM_000152.5(GAA):c.1564C>G (p.Pro522Ala)

ClinVar:371277

CAID:CA16041893

gnomAD: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Case 2, Boy, Death at 7 months old, Hispanic

DiseaseAssertion: Pompe disease

FamilyInfo: Parents were carriers of the variant in Patient 2 (Figure 2.C)

CasePresentingHPOs: HP:0002205, HP:0001945, HP:0000980, HP:0001290, HP:0000158, HP:0002791, HP:0002240, HP:0200128

(Recurrent respiratory infections, Fever, Pallor, Generalized hypotonia, Macroglossia, Hypoventilation, Hepatomegaly, Biventricular hypertrophy )

CaseHPOFreeText: Systolic and diastolic dysfunction.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Ejection fraction was 40%

Serum Creatine Kinase levels were 650 IU/L

GAA enzyme activity on dried blood spots was 0.6 pmol/L, below normal levels (normal range: 10.0- 49 pmol/L).

Variant: c.1987delC

ClinVar: N/A

CAID: N/A

gnomAD: N/A

ParentalGenotype: Both parents are carriers of the variant c.1987delC

PreviouslyPublished: N/A

Case#: Case 1, Boy, Death at 6-7 months old, Hispanic

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002240, HP:0001640, 0000961, HP:0002090, HP:0001270, HP:0031664, HP:0200128, HP:0001252

(Hepatomegaly, Cardiomegaly, Cyanosis, Pneumonia, Motor delay, Systolic heart murmur, Biventricular hypertrophy, Muscular Hypotonia)

CaseHPOFreeText: Heart failure, Systolic murmur grade II-III, Enlarged, EKG showed an inverted T wave from V4-V6 as well as AVF, suggesting left systolic overload.

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: Ejection fraction of 52%

Serum creatine kinase was 386 IU/L (mildly elevated)

GAA activity on dried blood spot was decreased (1.08 nmol/L; normal range: 1.5-10 nmol/L)

Whole exon and exon-intron boundaries direct sequencing revealed a homozygous single base deletion c.1987delC

Variant: c.1987delC

ClinVar: N/A

CAID: N/A

gnomAD: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: case 1, male, 3 months old at diagnosis, ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001638, HP:0001252 (cardiomyopathy, muscular hypotonia)

CaseHPOFreeText: (Associated with Pompe Disease): Interventricular septum hypertrophy, increased serum CK, increased serum tryptase

CaseHPOFreeText: (Infussion associated reactions) Urticarial rash, unresponsive to antihistamines and corticosteroids

CaseNotHPOs:

CaseNotHPOFreeText: Infusion associated reactions are not associated with an IgE mediated mechanism.

CasePreviousTesting:

GAA activity on fibroblast is 0.8 nmol/mg prot/h with a reference range of 64.4 ± 22.9 nmol/mg prot/h

GAA activity on lymphocytes is 2.2 nmol 4 Mu/mg prot/h with a reference range of 21.4 ± 6.2 nmol 4 Mu/mg prot/h

Variants:<br /> Variant 1: NM_000152.5(GAA):c.236_246del (p.Pro79fs)

ClinVar: 371302

CAID: 16041880

Variant 2: NM_000152.5(GAA):c.1655T>C (p.Leu552Pro)

ClinVar:279811

CAID: 8815429

gnomAD: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Case 2, male, 50 days old when diagnosed, ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001638, HP:0001252, HP:0000282 (cardiomyopathy, muscular hypotonia, facial edema)

CaseHPOFreeText:(Associated to Pompe disease) increased serum CK.

CaseHPOFreeText: (Infussion associated reactions) Generalized rash, cough and bronchospasm

CaseNotHPOs: N/A

CaseNotHPOFreeText: Infusion associated reactions are not associated with an IgE mediated mechanism.

CasePreviousTesting: See Table 1 for reports on GAA metabolic activity.

GAA activity in dried blood spots is 0 μmol/l/h with a reference range of 1.86–21.9 μmol/l/h

GAA activity on lymphocytes is 0.5 nmol 4 Mu/mg prot/h with a reference range of 21.4 ± 6.2 nmol 4 Mu/mg prot/h

Variant: c1124G>T (p.R375L)

ClinVar: N/A

CAID: N/A

gnomAD: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Patient 3, male, 21 year old, ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: No family history of muscle disease

CasePresentingHPOs: HP:0003236, HP:0100284

(Elevated serum creatine kinase, EMG: myotonic discharges

CaseHPOFreeText: Mild weakness (4/5) of iliopsoas muscles

Myotonic discharges in the lumbar paraspinal muscles

Elevated aspartate aminotransferase of 172 I/U ( Normal range 19–55 I/U)

Elevated alanine aminotransferase of 203 I/U (Normal range 19–72 I/U)

Serum CK was elevated at 1,373 U/L (normal range 70–185 U/L)

CaseNotHPOs:

CaseNotHPOFreeText: Normal alkaline phosphatase and γ-glutamyl transpeptidase levels.

Liver ultrasound and biopsy at an outside facility were normal

CasePreviousTesting: GAA level was 1.4 pmol/punch/h (normal range 10–49 pmol/punch/h)

Variant 1: NM_000152.5(GAA):c.-32-13T>G

ClinVar: 4027

CAID: CA116606

gnomAD: Hughest population MAF= 0.005541 (Ashkenazi Jewish)

Variant 2: NM_000152.5(GAA):c.877G>A (p.Gly293Arg)

ClinVar: 4036

CAID: CA116622

gnomAD: Highest population MAF= 0.00005704 (Latinos)

ParentalGenotype:N/A

PreviouslyPublished:N/A

Case#: Patient 2, Male, 71 year old, ethnicity unknown

DiseaseAssertion: Pompe disease

diagnosed at age 52 with SMA type III following an EMG reporting neurogenic changes and a muscle biopsy from a hamstring muscle that demonstrated denervation atrophy

FamilyInfo: N/A

CasePresentingHPOs: HP:0003701, HP:0003445

(Proximal muscle weakness, EMG:neuropathic changes

CaseHPOFreeText: Normal strength in the upper extremities with moderate weakness of hip flexion at 3/5, hip abduction 3–4/5, hip adduction 3–4/5, and hamstrings 4/5.

EMG showed myotonic discharges in the anterior tibialis, medial gastrocnemius, iliopsoas, tensor fasciae latae, and biceps brachii muscles.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

Staining for PAS and acid phosphatase was normal.

Serum CK was 208 U/L (normal range 70–185)

CasePreviousTesting: GAA activity was 1.3pmol/punch/h (normal 10–49 pmol/punch/h) and he was found to have 2 heterozygous mutations

Variant 1: NM_000152.5(GAA):c.-32-13T>G

ClinVar: 4027

CAID: CA116606

gnomAD: Highest population MAF= 0.005541 (Ashkenazi Jewish)

Variant 2: NM_000152.5(GAA):c.1841C>A (p.Thr614Lys)

ClinVar: 167113

CAID: CA234050

gnomAD: Highest population MAF= 0.00004784 (European nin-Finnish)

ParentalGenotype:N/A

PreviouslyPublished:N/A

Case#: Patient 1, woman, 58 years old, ethnicity unknown

DiseaseAssertion:Pompe disease

Was also misdiagnosed with adult-onset spinal muscular atrophy (SMA)

FamilyInfo: No family history of muscle disease

CasePresentingHPOs: HP:0003701, HP:0100284

(Proximal muscle weakness, EMG myotonic discharges)

CaseHPOFreeText: Denervation atrophy from a muscle biopsy

Weakness of hip flexion 2–3/5, hip abduction 2/5, and hip adduction 2/5

Myotonic discharges were in the lumbar paraspinals, vastus medialis, and tensor fasciae latae muscles.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: GAA enzyme activity assay was 1 pmol/punch/h (normal range 10–49 pmol/punch/h)

Her creatine kinase (CK) level at presentation had been elevated as high as 429 U/L (normal range 45–145)

Found with two mutations in the GAA gene

Variant: NM_000152.5(GAA):c.-32-13T>G

ClinVar: 4027

CAID: CA116606

gnomAD: Highest population MAF= 0.005541 (Ashkenazi Jewish)

Variant: NM_000152.5(GAA):c.525del (p.Glu176fs) Double check this variant

ClinVar: 4033

CAID: CA220406

gnomAD: N/A

ParentalGenotype:N/A

Previously Published: N/A

Case#: 87, Gender N/A, 6 months old when diagnosed, Asian

DiseaseAssertion:Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText:N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: The patient did not present any symptoms, diagnosed was made based on the predicted impact of the variant by PolyPhen-2

CasePreviousTesting: The GAA gene was sequenced using NGS and resequenced for confirmation using Sanger.

Dried Blood spot test found an GAA activity of 4.6 pmol/h/disk with a reference value of 6.5 pmol/h/disk

enzyme activity in fibroblast was recorded to be 5.4 nmol/h/mg protein.

Variants: Variant1: (Two mutated alleles with heterozygous mutations)

Variant1.1: NM_000152.5(GAA):c.752C>T (p.Ser251Leu)

ClinVar: 346310

CAID: CA8815007

gnomAD: Highest population MAF = 0.002234 (East Asian)

Variant1.2: NM_000152.5(GAA):c.761C>T (p.Ser254Leu)

ClinVar: 330447

CAID: CA8815009

gnomAD: Highest popu;ation MAF= 0.002235 (East Asians)

Variant2: NM_000152.5(GAA):c.2003A>G (p.Tyr668Cys)

ClinVar: 546808

CAID: N/A

gnomAD: N/A

ParentalGenotype:N/A

PreviouslyPublished:N/A

Case#: 84, Gender N/A, 6 months old when diagnosed, Asian

DiseaseAssertion: Pompe disease

FamilyInfo: Both parents were tested for variants in GAA

CasePresentingHPOs: N/A

CaseHPOFreeText:N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: The patient did not present any symptoms, diagnosed was made based on the predicted impact of the variant by PolyPhen-2

CasePreviousTesting: The GAA gene was sequenced using NGS and resequenced for confirmation using Sanger.

Dried Blood spot test found an GAA activity of 3.8 pmol/h/disk with a reference value of 6.5 pmol/h/disk

enzyme activity in fibroblast was recorded to be 3.0 nmol/h/mg protein.

Variants: Variant1: (Two mutated alleles with heterozygous mutations)

Variant1.1: NM_000152.5(GAA):c.752C>T (p.Ser251Leu)

ClinVar: 346310

CAID: CA8815007

gnomAD: Highest population MAF = 0.002234 (East Asian)

Variant1.2: NM_000152.5(GAA):c.761C>T (p.Ser254Leu)

ClinVar: 330447

CAID: CA8815009

gnomAD: Highest popu;ation MAF= 0.002235 (East Asians)

Variant2: C.1244C>T

ClinVar: N/A

CAID: N/A

gnomAD: N/A

ParentalGenotype: The c.752C>T+c.761C>T and c.1244C>T of subject ID 84 were derived from mother and father, respectively

PreviouslyPublished:N/A

Case#: 93, gender N/A, 6months old when diagnosed, Asian

DiseaseAssertion: Pompe disease

FamilyInfo: Both parents were carriers of mutations in the GAA gene. The patient inherited the mutations.

CasePresentingHPOs: N/A

CaseHPOFreeText: Symptoms were noted at the age of 2.7 months old

CaseNotHPOs: N/A

CaseNotHPOFreeText: The patient showed no symptoms but LOPD was diagnosed based on the predicted impact of the variants by PolyPhen-2

CasePreviousTesting: The GAA gene was sequenced using NGS and resequenced for confirmation using Sanger.

Dried Blood spot test found an GAA activity of 0.25 pmol/h/disk with a reference value of 6.5 pmol/h/disk

Variant1: NM_000152.5(GAA):c.317G>A (p.Arg106His)

ClinVar: 286481

CAID: CA8814849

gnomAD: MAF=0.0001094 in East Asian

Variant2: (COMBINATION OF MUTATIONS IN THIS ALLELE, DOUBT HERE)

Variant2.1: NM_000152.5(GAA):c.752C>T (p.Ser251Leu)

ClinVar: 346310

CAID: CA8815007

gnomAD: Highest population MAF = 0.002234 (East Asian)

Variant2.2: NM_000152.5(GAA):c.761C>T (p.Ser254Leu)

ClinVar: 330447

CAID: CA8815009

gnomAD: Highest population MAF= 0.002235 (East Asians)

ParentalGenotype: Father is heterozygous for c.317G>A (p.Arg106His).

Mother carries both mutations of c.[752C>T,761C>T].

PreviouslyPublished:N/A

Case#: Patient, female, 61 years old, ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0040213, HP:0010535, HP:0003326, HP:0002273, HP:0002877 (Hypopnea, Sleep Apnea, Myalgia, Tetraparesis, Nocturnal hypoventilation)

CaseHPOFreeText: Sleep Apnea-Hypopnea Syndrome (SAHS), predominantly proximal tetraparesis

CaseNotHPOs: N/A

CaseNotHPOFreeText: Serum measurements were normal, includind Creatine Phosphokinase levels (CPK)

CasePreviousTesting: GAA enzyme level 0.72 µkat/kg was significantly reduced in lymphocytes with a reference range of 4.8–13.3 µkat/kg protein. This test was done with maltase-glucoamylase inhibitor acarbose

All exons and flanking introns were bidirectionally sequenced after PCR amplification. "sequence-analysis of GAA transcripts"

Variant: c.1194+5G>A

ClinVar:

CAID:CA658795243

gnomAD:

ParentalGenotype:

PreviouslyPublished: N/A