GSD type III is due to mutation at AGL gene (Amylo-1, 6-glucosidase) and this result in dysfunction of liver and muscle. Four forms of GSD III have been observed till date. Liver function is accessed for prothrombin and transaminases levels and DNA is isolated from blood and analysis of AGL gene is performed clinically. Various imaging methods include ultrasonography of abdomen and electromyography. (Tegay D H and Jose R, 2009).
GSD type IV or Andersen disease is due to mutation at 3p12 and activity of GBE1 (glycogen-branching enzyme) is reduced. This results in failure and cirrhosis of liver. Various tests include CBC count and assessing albumin and bilirubin levels. CT and MRI scan help to notice hepatic cirrhosis. Prenatal testing and molecular diagnosis is performed. (Lerardi-Curto L, 2009)
GSD type V or McArdie disease is due to genetic mutation of PGYM gene at 11q13 that result in the deficiency of myophosphorylase. Laboratory tests include checking elevated serum creatine kinase levels and other tests include electromyography, muscle biopsy and 31P-NMR. (Copier E J, 2009)
The gene encoding muscle form of glycogen phosphorylase, PYGM is tested using molecular testing methods such as targeted mutational analysis, sequence analysis. (Arenas J et al, 2009)
GSD type VI in classic form is due to deficiency of liver phosphorylase; phosphorylase b kinase and mutations are observed in PHKA2, PHKB, and PHKG2 genes. Tests include assessing urine ketone levels and serum ketone bodies and liver volume quantitative tests by MRI or CT scan. Definitive methods include liver biopsy, enzyme analysis. (Lerardi-Curto L, 2010)
Genetic testing of PYGL gene that is associated with the disease is done for accurate results. (Dali A I and Weinstein D A, 2009)
GSD type VII also called tarui disease; is due to deficiency of phosphofructokinase enzyme that plays key role in regulating glycolysis. The disease is caused due to frameshift mutations in the gene that codes for PFK-M subunit at locus 12p13. Definite diagnosis include muscle biopsy and biochemical test involved is to assess the of serum creatine kinase, bilirubin levels and imaging tests like brain imaging scans and phosphorous 31-NMR are useful in diagnosis. (Lerardi-Curto L, 2009)
Screening tests usually performed are glucagon tolerance tests and other biochemical data obtained from serum is evaluated and best possibility to diagnose hepatic GSD is using peripheral blood cells. (Maire I et al., 1991)
Controls used in diagnostic methods are usually of age and sex matched and were also checked for their exercise levels with the patients. As soon as the tests finish comparison is made between patients and controls and these tests are usually based on type of GSD. (Mundy H R et al., 2005).
b) Family1
Based on the data provided it is clearer that Philip has disease with genotype rr and this provide information that their children are carriers of the disease. It’s clearly mentioned that III 2 and III 6 are grand children of Philip. This shows the only possibility of Philip being father to Joe Smith and other with carrier genotype.
Joe Smith is married to Ethel of normal genotype and their child is normal with 50% of them carriers i.e. Jack (III 2) and III 3 are carriers. Philip’s another child is also carrier and when he is married to another carrier there is a 1 in 4 chance of their children getting affected i.e. III 6.
Jack (Rr) is married to his cousin III 6 (rr) and their offspring has chance of 50% getting affected that resulted in death of IV1 (rr) and IV3 (rr)
Family 2
As per the case Jennie Jones has GSD with genotype rr as disease is autosomal recessive and Frederick also has the same phenotype. It shows that both of them have disease with genotype rr.
Though they both are not related to each other, they have recessive genes responsible for the disease and offspring has 100% risk of getting the disease.
Family 3
As per given, both Adam Clark and his wife do not have any signs of GSD not even their respective families do. When there is no sign of GSD in families definitely they don’t have any recessive gene in their genotype, as GSD is autosomal recessive inborn metabolic disease.
Even though they come from a population with GSD it’s not going to affect an individual’s genotype. From this I would definitely say they are at 0% risk
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