Case#: P 17, Female, 5.5 mo nths old when started ERT (62.8 months old when last reported), German

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: P:0001639 , HP:0001252 , HP:0003701, HP:0006532

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Recurrent Pneumonia)

CaseHPOFreeText: Recurrent pneumonia was a complication during ERT

Best and last motor status was walking

CaseNotHPOs: N/A

CaseNotHPOFreeText: Did not required tube feeding nor ventilation

CasePreviousTesting: CRIM status was unknown

Antibody titer 1:800

Variant: NM_000152.5(GAA):c.1978C>T (p.Arg660Cys)

ClinVar: 558604

CAID: CA8815561

gnomAD: MAF=0.00005554 in East Asian

ParentalGenotype: Both the paternal and maternal allele carried the NM_000152.5(GAA):c.1978C>T (p.Arg660Cys) Variant

PreviouslyPublished: N/A

Case#: P 11, Male, 2.6 months old when started ERT (Died at 14.1 months old), German

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0011951

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Aspiration pneumonia )

CaseHPOFreeText: AR IV

Patient required ventilation and tube feeding

No motor activity reported

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CRIM status is negative

Antibody titer is 1:51.200

Variant: NM_000152.5(GAA):c.1548G>A (p.Trp516Ter)

ClinVar: 189025

CAID: CA274281

gnomAD: MAF=0.00001552 in European non-Finnish

ParentalGenotype: Both the paternal and maternal allele carry the variant c.1548G>A (p.Trp516Ter)

PreviouslyPublished: N/A

Case#: P 3, Male, 4.9 months when started ERT (122.1 months old at publication date), Ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: Table 1 includes parental genotype

CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0002028

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Chronic diarrhea )

CaseHPOFreeText: Chronic diarrhea was a complication during ERT

Patient best and last/current status was being able to sit

CaseNotHPOs: N/A

CaseNotHPOFreeText: Patient did not required tube feeding

Patient did not required ventilation

CasePreviousTesting: CRIM status is positive in patient

Antibody titer is 1:200

Variant 1: c.IVS17 + 102_IVS18 + 3

ClinVar: N/A

CAID: 657307

gnomAD: N/A

Variant 2: c.1465G>T (p.Asp489Tyr)

ClinVar: N/A

CAID: CA401366871

gnomAD: N/A

ParentalGenotype: The maternal allele of the patient carried the c.IVS17 + 102_IVS18 + 31 Variant

The paternal allele of the patient carried the c.1465G>T (p.Glu489Ter) Variant

PreviouslyPublished: N/A

Case#: P 7, Female, 2.3 months old when started ERT (90.6 months old at publication date), ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0031846, HP:0030242

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Femur fracture, Portal vein thrombosis)

CaseHPOFreeText: Femur fracture and Port thrombosis were complications during ERT

Best motor status was walking, last motor status was sitting

Patient required ventilation

CaseNotHPOs: N/A

CaseNotHPOFreeText: Did not required tube feeding

CasePreviousTesting: CRIM status is positive

Antibody titer is 1:800

Variant: NM_000152.5(GAA):c.1933G>A (p.Asp645Asn)

ClinVar: 188728

CAID: CA273892

gnomAD: Highest population MAF= 0.00006599 in Africans

ParentalGenotype: Both the paternal and maternal allele carried the variant c.1933G>A (p.Asp645Asn)

PreviouslyPublished: N/A

Case#: P 8, Female, 3.7 months old when started ERT (Died at 36.8 months), German

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0006532

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Recurrent pneumonia)

CaseHPOFreeText: Recurrent pneumonia and GER were complications during ERT

Patient required ventilation and tube feeding

The best and last motor status was sitting.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CRIM status is positive in patient

Antibody titer is 1:4,000

Variant: NM_000152.5(GAA):c.266G>A (p.Arg89His)

ClinVar: 283219

CAID: CA8814833

gnomAD: Highest population MAF= 0.001168 in Ashkenzai Jewish

Variant: c.104T>C (p.Phe35Ser)

ClinVar: N/A

CAID: CA401360259

gnomAD: N/A

ParentalGenotype: The maternal allele carried the c.266G>A variant

The paternal allele carried the c.104T>C variant

PreviouslyPublished: N/A

Case#: P 15, female. 4.7 months old when started ERT (Died at 8.1 months old)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0100806

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Sepsis )

CaseHPOFreeText: Sepsis, Asystolia, Port infection and AR IV were complications during ERT

Required tube feeding

No motor activity reached

CaseNotHPOs: N/A

CaseNotHPOFreeText: Did not required ventilation

CasePreviousTesting: CRIM status was negative

Antibody titer was unknown

Variant: NM_000152.5(GAA):c.1687C>T (p.Gln563Ter)

ClinVar: 370357

CAID: CA16041895

gnomAD: N/A

ParentalGenotype: Both the paternal and maternal allele carried the variant c.1687C>T (p.Gln563Ter)

PreviouslyPublished: N/A

Case#: P 10, Male, 7.0 months old when started ERT (Died at 21.1 months old)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0006532

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Recurrent pneumonia )

CaseHPOFreeText: Patient required tube feeding

Recurrent pneumonia was a complication during ERT

Patient did not achieved motor function

CaseNotHPOs: N/A

CaseNotHPOFreeText: Patient was not ventilated

CasePreviousTesting: CRIM status was unknown

Antibody titer was not available

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

ClinVar: 4034

CAID: CA340130

gnomAD: Highest population MAF = 0.001891 (African)

ParentalGenotype: Both the paternal and maternal allele carried the c.2560C>T (p.Arg854Ter) Variant

PreviouslyPublished: N/A

Case#: P 16, Female, 3.4 months old when started ERT (Died at 27.0 months), German

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: P:0001639 , HP:0001252 , HP:0003701, HP:0002090

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Pneumonia)

CaseHPOFreeText: Pneumonia, deterioration and AR III were complications during ERT)

Ventilation and tube feeding were necessary

Best motor status was sitting

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CRIM status was positive

Antibody titer 1:5,600

Variant: NM_000152.5(GAA):c.1548G>A (p.Trp516Ter)

ClinVar:<br /> 189025

CAID: CA274281

gnomAD: MAF=0.00001552 in European non-Finnish

Variant: c.IVS14 + 20A>G (old nomenclature)

ClinVar: N/A

CAID: N/A

gnomAD: N/A

ParentalGenotype: The maternal allele carried the c.IVS14 + 20A>G variant

The paternal allele carried the c.1548G>A Variant

PreviouslyPublished: N/A

Case#: P 6, Male, 2.8 months when started ERT (Died at 18.2 months old), ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0002090

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Pneumonia)

CaseHPOFreeText: Pneumonia with deterioration was a complication during ERT. Also patient suffered progressive hypertrophic cardiomyopathy.

AR IV

Required ventilation

Best motor status was being able to sit

CaseNotHPOs: N/A

CaseNotHPOFreeText: Patient did not required tube feeding

CasePreviousTesting: CRIM status was unknown

Antibody titer was 1:84,000

Variant: NM_000152.5(GAA):c.915G>A (p.Gly305=)

ClinVar: 188478

CAID: CA198779

gnomAD: N/A

ParentalGenotype: Bothe the maternal an paternal allele of the GAA gene carried the variant c.915G>A (p.Gly305=)

PreviouslyPublished: N/A

Case#: P 2, Female, 4.7 months old when started ERT (113.7 months old at publication date), ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: Table 1 includes parental genotype

CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0002090

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Pneumonia)

CaseHPOFreeText: Aspiration pneumonia was a complication during ERT.

Patient requires tube feeding.

Patient's best and current motor status is being able to sit.

CaseNotHPOs: N/A

CaseNotHPOFreeText: Patient has not required ventilation

CasePreviousTesting: CRIM status is positive in patient

Antibody titer is 1:1.200

Variant 1: NM_000152.5(GAA):c.1799G>A (p.Arg600His)

ClinVar: 370130

CAID: CA8815482

gnomAD: Highest population MAF= 0.00003267 in South Asians

Variant 2: c.1859G>A

ClinVar: N/A

CAID: N/A

gnomAD: N/A

ParentalGenotype: Mother is the carrier of the c.1799G>A (p.Arg600His) Variant

Father is the carrier of the c.1859G>A variant

PreviouslyPublished: N/A

Case#: P 14, Male, 1.5 months old when started ERT (Died at 41.8 months old), German

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0002090

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Pneumonia)

CaseHPOFreeText: Pneumonia and deterioration were complications during ERT

Required ventilation

CaseNotHPOs: N/A

CaseNotHPOFreeText: Did not required tube feeding

CasePreviousTesting: CRIM Status and Antibody titer are unknown

Variant: NM_000152.5(GAA):c.1978C>T (p.Arg660Cys)

ClinVar:<br /> 558604

CAID: CA8815561

gnomAD: MAF=0.00005554 in East Asian

ParentalGenotype: Both the paternal and maternal allele carry the variant c.1978C>T (p.Arg660Cys)

PreviouslyPublished: N/A

Case#: P 5, Male, 0.9 months old when started ERT (76.9 months old at publication date), Ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0006532

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Recurrent pneumonia)

CaseHPOFreeText: Recurrent pneumonia was a complication during ERT.

AR III

Patient requires tube feeding and is ventilated

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CRIM status is unknown

Antibody titer is 1:12,000

Variant: NM_000152.5(GAA):c.2662G>T (p.Glu888Ter)

ClinVar: 578595

CAID: CA8815829

gnomAD: Highest population MAF= 0.0002719 (East asian)

ParentalGenotype: Both the paternal and maternal allele carry the c.2662G>T (p.Glu888Ter) Variant

PreviouslyPublished: N/A

Case#: P 18, Male, 1.4 months old when started ERT (Died at 36.4 months old)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0006532

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Recurrent Pneumonia)

CaseHPOFreeText: Recurrent pneumonia was a complication during ERT

Best motor status was walking

CaseNotHPOs: N/A

CaseNotHPOFreeText: Did not required ventilation nor tube feeding

CasePreviousTesting: CRIM status was positive

Antibody titer was unknown

Variant: NM_000152.5(GAA):c.896T>C (p.Leu299Pro)

ClinVar: 180144

CAID: CA273686

gnomAD: N/A

ParentalGenotype: Both the paternal and maternal allele carried the variant NM_000152.5(GAA):c.896T>C (p.Leu299Pro)

PreviouslyPublished: N/A

Case#: Patient 4, Female, 10 days old at diagnosis, African American

DiseaseAssertion: Pompe disease

FamilyInfo:N/A

CasePresentingHPOs: HP:0009062, HP:0001638

(Infantile axial hypotonia, Cardiomyopathy)

CaseHPOFreeText: Before ERT patient withdraws extremities to stimulation, contractures of large joint of upper and lower extremities, weak grasp. Also patient was invasively ventilated. Baseline – G-tube feeds and continues

Currently patient is off ventilator 10-12 hours a day. Sits with support; and has minimal capacity for weight bearing on lower extremities. G tube feed.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: No GAA measurement

Variant 1: M_000152.5(GAA):c.525del (p.Glu176fs)

ClinVar: 4033

CAID: CA220406

gnomAD: N/A

Variant 2: NM_000152.5(GAA):c.2560C>T (p.Arg854Ter)

ClinVar: 4034

CAID: CA340130

gnomAD: Highest population MAF= 0.001891 (African)

ParentalGenotype:N/A

PreviouslyPublished:N/A

Case#: Patient 6, Female, 5.5 months old at diagnosis, Asian

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001252, HP:0001638

(Muscular hypotonia, Cardiomyopathy)

CaseHPOFreeText:

Previous to ERT, patient was invasively ventilated, and had . Also Aspiration and penetration with feeding and started on NG tube feeds at baseline

Current patient has marked axial and peripheral hypotonia, G-tube feeds and requires BiPAP at night. Patient has near-complete lower extremity immobility

CaseNotHPOs: N/A

CaseNotHPOFreeText: Antigravity movement in arms

CasePreviousTesting: N/A

Variant: NM_000152.5(GAA):c.525_526del (p.Asn177fs) Please double check

ClinVar: 189057

CAID: CA274328

gnomAD: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Patient 2, Male, 2.5 months old at diagnosis, African Canadian

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001638, HP:0032988

(Cardiomyopathy, Persistent head lag)

CaseHPOFreeText: antigravity movements arms>legs

Previous to ERT NG tube feeding was necessary due to aspiration, after ERT patient uses a GJ tube.

Patient requires oxygen and BiPAP at night.

CaseNotHPOs: N/A

CaseNotHPOFreeText: Patient can bear its weight independently.

CasePreviousTesting: No GAA measurement

Variant: NM_000152.3:c.546+2T>C

ClinVar: N/A Double check

CAID: CA401361919

gnomAD: N/A

ParentalGenotype:N/A

PreviouslyPublished:N/A

Case#: Patient 7, Female, diagnosed at 3 months old (died at 15 months old), African American

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001638 (Cardiomyopathy)

CaseHPOFreeText: Previous to ERT patient did not required oxygen support. Patient needed Invasive ventilation at week 38 ERT until death 2 months later.

Previous to ERT and during it patient was unable to independently hold head or sit unsupported.

Previous to ERT NG tube feeds at age 3 months due to aspiration. During ERT patient used a GJ tube

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

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

ClinVar: 4034

CAID: CA340130

gnomAD: Highest population MAF= 0.001891 (African)

ParentalGenotype:N/A

PreviouslyPublished: N/A

Case#: Patient 5, Female, 3.0 months old at diagnosis, African American

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0032988, HP:0001638

(Persistent head lag, Cardiomyopathy)

CaseHPOFreeText:

Previous to ERT patient was invasively ventilated, patient was unable to sit or roll over. NJ feeds started at age 3 months

Currently patient requires Oxygen and BiPAP at night. Stands with support and uses G tube for feeding.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: No GAA measurement

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

ClinVar: 4034

CAID: CA340130

gnomAD: Highest population MAF= 0.001891 (African)

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Patient 3, Female, 2 months old at diagnosis, Caucasian

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001252, HP:0001638

(Muscular hypotonia, Cardiomyopathy)

CaseHPOFreeText: floppy baby, no head or neck control

NG tube feeds started at age 1.4 months, currently the patient orally feeds.

Before ERT patient needed oxygen, currently the patient does not need respiratory support.

CaseNotHPOs:

CaseNotHPOFreeText:

Patient ambulates independently

No infusion associated reactions to ERT

CasePreviousTesting: No GAA measurement

Variant: NM_000152.5(GAA):c.236_246del (p.Pro79fs)

ClinVar: 371302

CAID: CA16041880

gnomAD: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Patient 1, female, 2.5 months of age at diagnosis, Hispanic

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001638, HP:0032988, HP:0001252, HP:0001270, HP:0002015, HP:0012378

(Cardiomyopathy, Persistent head lag, Muscular hypotonia, Motor delay, Dysphagia, Fatigue)

CaseHPOFreeText: NG tube feeding was left after Enzyme Replacement Therapy (ERT).

Cardiac status at base line was 160 LVMI g/m^2, after ERT IT WAS 81 LVMI g/m^2

Patient needed oxygen at baseline, no respiratory support at ERT.

one episode of Infusion Associated Reactions (IARs) to ERT.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting:

Variant 1: NM_000152.5(GAA):c.2608C>T (p.Arg870Ter)

ClinVar: 189009

CAID: CA274250

gnomAD: Highest population MAF= 0.00004888 (European non-Finnish)

ParentalGenotype:N/A

PreviouslyPublished:N/A

Case#: V.4, female, age of diagnosis 7 months, Moroccan

DiseaseAssertion: Pompe disease

FamilyInfo: Pedigree (figure 2). V.4 parents are cousins (IV.2 and IV.3). V.4 had a cousin (V.3) that died at 8 months of age and was diagnosed with HCM. V.3 parents (IV.1 and IV.4) are cousins. IV.2, IV.3, IV.1 and IV.4 were all heterozygous for the GAA mutation c.236_246del (p.Pro79ArgfsX13). V.4 was homozygous for the mutation.

CasePresentingHPOs: HP:0005157, HP:0001290

(Concentric hypertrophy, generalized hypotonia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: hypotonia without facial dysmorphia or other associated abnormalities.

The heart was structurally normal and no valvular anomalies were observed.

CasePreviousTesting: whole exome sequencing (WES), Sanger sequencing. No metabolic screening was performed.

Molecular analysis of SMN gene excluded Spinal muscular atrophy, one of the major causes of neonatal hypotonia in Morocco.

Variant: NM_000152.5 c.236_246del (p.Pro79ArgfsX13)

ClinVar: 371302

CAID: CA16041880

gnomAD: N/A

ParentalGenotype: Both parents are heterozygous for .236_246del (p.Pro79ArgfsX13)

PreviouslyPublished: N/A