Info

16p11-12, Gene: PHKG2

Type XI (Fanconi-Bickel syndrome)

Glucose transporter 2

AR, 3q26.1-26.3, Gene: GLUT2

Type GSD 0

Glycogen synthase

AR, 12p12.2, Gene: GYS2

aAR: autosomal recessive.

aAR: autosomal recessive.

forms of the disease presenting with different ages of onset and clinical severity have been identified.1-12'13-1

Clinical Findings

The infantile form presents with progressive hypertrophic cardiomyopathy, generalized hypotonia with muscle wasting' hepatomegaly' and macroglossia' followed by a rapid, progressive course. Death usually occurs before the second year of life as a result of cardiorespiratory failure.

The juvenile form presents in early childhood, with progressive muscle weakness including the diaphragm, but no cardiac involvement. Affected patients usually die before puberty from respiratory failure.[12,13]

In the adult form, the presenting symptom may resemble the muscle weakness of limb-girdle muscular dystrophy or a respiratory insufficiency. Definitive diagnosis for GSD type II requires enzyme analysis of skin fibroblasts. In general, enzyme deficiency is more severe in the infantile form than the late-onset juvenile and adult forms.

Genetics

GSD II is autosomal recessive. The gene that encodes acid maltase (GAA) is located on chromosome 17q25.[14] Genetic and biochemical heterogeneity has been observed in GSD II without clear correlation to clinical phenotypes. More than 70 disease-causing mutations have been described,[14] and most are private family mutations. However, some common mutations exist in specific ethnic groups, including Dutch (del exon 18), Asians (C1935A), and African-Americans (C2560T), which could be used for carrier detection and diagnosis.[15]

Major clinical presentation

Enzymatic diagnosis (tissue)

Gene-based diagnosis

Hepatomegaly, hypoglycemia, elevated blood lactate, cholesterol, triglycerides and uric acid Same as Ia, with additional findings of neutropenia and neutrophil dysfunction

Cardiomegaly, hypotonia, muscle weakness, macroglossia;

onset birth to 6 months

Myopathy, variable cardiomyopathy;

onset childhood.

Myopathy, respiratory insufficiency; onset adulthood

Childhood hepatomegaly, growth retardation, muscle weakness, hypoglycemia, hyperlipidemia, elevated transaminases

Liver symptoms same as IIIa:

no muscle symptoms

Failure to thrive, hepatomegaly, splenomegaly, progressive cirrhosis, elevated transaminases Exercise intolerance, muscle cramps, increased fatigability Hepatomegaly, mild hypoglycemia, hyperlipidemia, and ketosis Exercise intolerance, muscle cramps, myoglobinuria, hemolytic anemia Hepatomegaly, mild hypoglycemia, hyperlipidemia, and ketosis

Yes (blood, muscle, liver, skin fibroblasts)

Yes (muscle, skin fibroblasts)

Yes (skin fibroblasts)

Yes (blood, liver, muscle)

Yes (liver)

Yes (liver, muscle, skin fibroblasts) Yes (muscle)

Yes (Liver)

Yes (muscle)

Yes (blood, liver)

Mutation screen

Mutation screen

Mutation screen and DNA sequencing Mutation screen and DNA sequencing Mutation screen and DNA sequencing DNA Sequencing

Mutation screen

Gene sequencing

Mutation screen

Gene sequencing

Mutation screen and DNA sequencing DNA sequencing

Hepatomegaly, enlarged kidneys, rickets, renal fanconi syndrome Hyperketotic hypoglycemia in infancy

Yes (liver)

DNA sequencing DNA sequencing

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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