Glycogen storage disease type II diagnostic study of choice

Jump to: navigation, search

Glycogen storage disease type II Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Glycogen storage disease type II from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Glycogen storage disease type II diagnostic study of choice On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Glycogen storage disease type II diagnostic study of choice

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Glycogen storage disease type II diagnostic study of choice

CDC on Glycogen storage disease type II diagnostic study of choice

Glycogen storage disease type II diagnostic study of choice in the news

Blogs on Glycogen storage disease type II diagnostic study of choice

Directions to Hospitals Treating Glycogen storage disease type II

Risk calculators and risk factors for Glycogen storage disease type II diagnostic study of choice

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Overview

Acid α-glucosidase (GAA) activity in fibroblast of a dried blood sample is the gold standard test for the diagnosis of glycogen storage disease type 2. Decreased activity of GAA in fibroblasts a dried blood sample is confirmatory of glycogen storage disease type 2.

Diagnostic Study of Choice

Gold standard

  • Acid α-glucosidase (GAA) activity in fibroblast of a dried blood sample is the gold standard test for the diagnosis of glycogen storage disease type 2.[1][2]
  • The following result of acid α-glucosidase (GAA) activity in fibroblast of a dried blood sample is confirmatory of glycogen storage disease type 2:

Diagnostic algorithms


Algorithms for diagnostic approach of glycogen storage disease type 2[3]
Diagnostic algorithm for Infantile onset glyogen storage disease type II
COMMON PRESENTING SYMPTOMS
CARDIOVASCULAR
Cardiomegaly;
Congestive heart failure;
Arrhythmias such as
supraventricular
tachycardia;
Cardiac arrest during
surgery.
 
PULMONARY
Frequent infections;
Respiratory distress/
insufficiency.
 
NEUROLOGICAL
Hypotonia;
Developmental delay;
Gross motor delay;
Loss of early motor milestones.
 
GASTROINTESTINAL
Failure to thrive;
Feeding difficulties.


PERTINENT PATIENT FINDNGS
CARDIOVASCULAR
Murmur, gallop, pulsatile
precordium, excessive
sweating (cardiac related);
Cardiomegaly;
Cardiomyopathy;
(hypertrophic +/- LVOTO)
progressing to dilated
cardiomyopathy.
 
PULMONARY
Progressive respiratory
involvement, nasal flaring;
Use of accessory
muscles, IC and SC
retractions, decreased
breath sounds in LLL;
Coarse breath sounds.
 
NEUROLOGICAL
Delayed motor
milestones
Hypotonia, head lag,
floppy baby with ability to
"slip through", frog leg
position, hypertrophy of
gastrocnemius muscle.
 
GASTROINTESTINAL
Macroglossia, open
mouth, low facial tone,
decreased gag reflex,
failure to thrive, poor suck
and swallow, difficulty
feeding with pooling of
oral secretions;
hepatomegaly.


INITIAL CLINICAL FINDINGS AND INVESTIGATIONS
 
 
 
 
 
 
 
 
 
 
 
If GAA present, follow-
up with confirmatory
testing, if strong clinical
suspicion.
 
 
 
CLINICAL STUDIES
Chest X-ray- Cardiomegaly;
EKG - huge R wave, short PR interval and broad
QRS complex;
Echocardiography - cardiomyopathy
Electrophysiology (EMG/NCS) - myopathy.
 
LABORATORY (BLOOD OR URINE)
Elevated CK, AST, ALT, LDH (in blood)
Glc4 (in urine);
GAA activity in dried blood spots.
lymphocytes, or leukocytes with blocking
antibodies to neutral maltase;
Mutation testing in familial mutation
known
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If GAA absent, obtain
confirmatory studies for
definitive diagnosis.
 
 


CONFIRMATOY STUDIES
DNA
GAA mutation testing
 
ENZYMOLOGY
GAA activity testing in fibroblasts or muscle
(the gold standard). Caution with muscle
biopsy is needed sue to anesthesia risk.
 
HISTOLOGY/
HISTOCHEMISTRY

Increased lysosomal glycogen
Vacuolated cells
Adapted from GENETICS IN MEDICINE[3]


ABBREVIATIONS: LVOTO - left ventricular outlet tract obstruction; IC - intercostal; SC - subcostal; LLL - left lower lung; EMG - Electromyography; NCS - Nerve conduction study; GAA - acid-alpha glucosidase; CK - creatine kinase; AST - aspartate aminotransferase; ALT - alanine aminotransferase


Diagnostic algorithm for Late onset (>1 year) glyogen storage disease type II
COMMON PRESENTING SYMPTOMS
PULMONARY
Frequent infections;
Respiratory insufficiency/distress;
Sleep apnea;
Somnolence
Morning headaches.
 
MUSCULOSKELETAL
Limb girdle weakness
Back pain;
Exercise tolerance;
Rigid spine syndrome.
 
GASTROINTESTINAL
Feeding and swallowing difficulties;
Poor weight gain.
 


PERTINENT PATIENT FINDNGS
RESPIRATORY
Respiratory insufficiency;
orthopnea, sleep apnea;
exertional dyspnea;
Weak cough.
 
MUSCULOSKELETAL
Progressive proximal limb-girdle
muscle weakness (lower
extremities. upper extremities;
gain abnormalities; exercise
intolerance; lordosis/scoliosis;
hypotonia; lower back pain;
Gower's sign.
 
GASTROINTESTINAL
Difficulty maintaining
normal weight;
Difficulty chewing or jaw
muscle fatigue;
Decreased gag reflex;
hepatomegaly.
 
CARDIOVASCULAR
Infrequent
cardiomegaly
(juveniles).


INITIAL CLINICAL FINDINGS AND INVESTIGATIONS
 
 
 
 
 
 
 
 
 
 
 
If GAA present, follow-
up with confirmatory
testing, if strong clinical
suspicion.
 
 
 
CLINICAL STUDIES
Lung function testing lying and sitting;
Muscle strength testing;
Electrophysiology (EMG/NCS) - myopathy;
Muscle biopsy - histology and
histochemistry.
 
LABORATORY (BLOOD OR URINE)
Elevated CK, AST, ALT, LDH (in blood)
Glc4 (in urine);
GAA activity in dried blood spots,
lymphocytes, or leukocytes with
blocking antibodies to neutral maltase;
Mutation testing in familial mutation
known
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If GAA absent, obtain
confirmatory studies for
definitive diagnosis.
 
 


CONFIRMATOY STUDIES
DNA
GAA mutation testing
 
ENZYMOLOGY
GAA activity testing in fibroblasts or muscle
(the gold standard);
ClinicaL coorelation with test result is required.
 
HISTOLOGY/
HISTOCHEMISTRY

(dependent on the site of biopsy)
Increased lysosomal glycogen;
Vacuolated cells
Adapted from GENETICS IN MEDICINE[3]

ABBREVIATIONS: EMG - Electromyogtaphy; NCS - Nerve conduction study; GAA - acid-alpha glucosidase; CK - creatine kinase; AST - aspartate aminotransferase; ALT - alanine aminotransferase

References

  1. Pompe Disease Diagnostic Working Group. Winchester B, Bali D, Bodamer OA, Caillaud C, Christensen E; et al. (2008). "Methods for a prompt and reliable laboratory diagnosis of Pompe disease: report from an international consensus meeting". Mol Genet Metab. 93 (3): 275–81. doi:10.1016/j.ymgme.2007.09.006. PMID 18078773.
  2. Kallwass H, Carr C, Gerrein J, Titlow M, Pomponio R, Bali D; et al. (2007). "Rapid diagnosis of late-onset Pompe disease by fluorometric assay of alpha-glucosidase activities in dried blood spots". Mol Genet Metab. 90 (4): 449–52. doi:10.1016/j.ymgme.2006.12.006. PMID 17270480.
  3. 3.0 3.1 3.2 ACMG Work Group on Management of Pompe Disease. Kishnani PS, Steiner RD, Bali D, Berger K, Byrne BJ; et al. (2006). "Pompe disease diagnosis and management guideline". Genet Med. 8 (5): 267–88. doi:10.109701.gim.0000218152.87434.f3 Check |doi= value (help). PMC 3110959. PMID 16702877.

Linked-in.jpg