Glycogen Storage Disease

Glycogen Storage Disease (GSD) and Homoeopathy © Dr. Rajneesh Kumar Sharma Homoeo Cure & Research Centre P. Ltd. NH 74, Moradabad Road, Kashipur (Uttaranchal) 244713 India Ph- 05947- 275535, 260327, 274338, 277418 Fax- 274338, 275535; Cells- 98 976 18594, 98 976 21896 [email protected], [email protected] The glycogen storage disease is the abnormal storage of glycogen in the body tissues. Glucose being major source of energy; it is stored in the form of glycogen and later released in the form of glucose with the help of enzymes, the process known as gluconeogenesis. Glycogen is a complex material composed of glucose molecules linked together in long chains with many branches off the chains. Glycogen is found mainly in liver and muscle cells, while the kidneys and intestines are minor storage sites. In Glycogen Storage Disease (GSD) there is inherited absence or deficiency of any of the enzymes responsible for glycogenesis or glycogenolysis, needed by the body during exercise or between meals. These enzyme defects lead to abnormal tissue concentrations of glycogen or to structurally abnormal forms of glycogen. The enzyme may be important in all cells of the body, or cells found specifically in liver or muscle tissue. Thus, the many forms of GSD can be described as affecting primarily the liver, the muscles, or both. In all types of GSD, also called as glycogenosis, the body is not able to produce sufficient glucose in the blood stream or to utilize glucose as a source of energy. Diagnosis of the type of GSD is made on the basis of symptoms, physical examination and biochemical tests. A muscle or liver biopsy confirms the actual enzyme defect. There are about eleven known types of GSD, which are classified by a number, by the name of the defective enzyme, or by the name of the author who first described the condition. Almost all forms of GSD occur when a child inherits the affected gene.

Glycogen Storage Disease Type I (GSD Type I) Synonyms: o o o o

von Gierkes disease Hepatorenal Glycogenosis Glucose-6-Phosphatase Deficiency Glycogen Storage Disease Type I Glycogenosis

In this type the enzyme glucose-6-phosphatase is defective in the liver, kidney, and small intestine, where it normally functions. However, the metabolic problem is centered in the liver. Patients with Type I GSD are unable to release glucose from glycogen. They cannot maintain their blood glucose levels and within a few hours after eating develop hypoglycemia (low blood sugar). The low levels of glucose in the blood of these patients often result in chronic hunger, fatigue, and irritability that is especially noticeable in infants. Symptoms of hypoglycemia only begin to appear when the interval between feedings increases and the infant sleeps through the night or when an illness prevents normal feeding routine. If the blood sugar falls to a low enough point, some patients may have seizures. Since Type I patients are able to store glucose as glycogen but not release it normally, with time the stored glycogen builds up in the liver. Hormones, lactic acid, triglycerides, and other products are increased in the blood as the body attempts to raise blood sugar. Along with the glycogen Fats are stored in the liver, which leads to enlargement of the liver. The liver does its many other functions normally, and there is not usually any evidence of liver failure. Due to glycogen accumulation the kidneys are also enlarged. The continued presence of hypoglycemia eventually leads the body to experience severe biochemical abnormalities and delayed growth and development. Untreated patients may have muscle wasting and increased body fat. GENERALS - DEVELOPMENT, arrested agar.;1 cupr.;1 bac.;1 cupr.;1 bar-c.;2 des-ac.;1 bar-c.;2 des-ac.;1 borx.;1 kali-c.;1 borx.;1 kreos.;1 bufo;1 lac-d.;1 calc.;2 med.;1 calc-p.;3 nat-m.;1 caust.;1 nat-m.;1 chin.;1 nep.;1

nep.;1 ph-ac.;1 phos.;2 pin-s.;1 sil.;2 sulfa.;1 sulfa.;1 sulph.;1 thyr.;1 vip.;1 vip.;1

When blood studies are done, it is discovered that there is usually a low blood sugar, elevated blood lactic acid, elevated cholesterol and other fats, and elevated uric acid concentration. High blood pressure has also been seen in a number of patients and when this occurs, appropriate treatment must be given. GENERALS - URIC ACID diathesis, lithemia berb.;1 lyc.;2 chinin-s.;1 lysd.;1 coc-c.;1 lysd.;1 coc-c.;1 nat-s.;1 fab.;1 sep.;1

skook.;1 thlas.;1 urt-u.;1

Patients with Type Ib Glycogen Storage Disease can develop frequent bacterial and fungal infections, due to abnormal functioning of the white blood cells. They may also develop chronic pancreatitis, chronic inflammatory bowel disease, and Crohn's disease. ABDOMEN - INFLAMMATION - Pancreas atro.;2 iod.;2 bar-m.;1 iris;2 con.;2 kali-i.;2

merc.;2 spong.;3

ABDOMEN - INFLAMMATION - Gastroenteritis aeth.;1 ant-t.;1 aloe;1 antip.;1 ant-t.;1 apis;1

apom.;1 ars.;1

The diagnosis of Type I GSD always includes blood studies, x-rays including some of the kidneys, measurements, and ultrasound of the liver. Gene-based mutation analysis can be used to diagnose the majority of Type I patients, while liver biopsy analysis may be needed in some cases. The treatments of Type I Glycogen Storage Disease are aimed at correcting the biochemical abnormalities and promoting growth and development. Current treatments consist of providing a continuous source of glucose by giving the patient glucose drinks frequently during the day and, in most cases, continuously overnight. Glucose drinks may replace these glucose feedings with uncooked cornstarch doses, mixed in water, Kool-Aid etc.

Glycogen Storage Disease Type II (GSD Type II) Synonyms: Pompe Disease Acid Maltase Deficiency - AMD It is an inborn error of metabolism that belongs to lysosomal storage disorders. Every cell in our body contains vesicles called lysosomes those digest the waste products of the cell. Type II GSD is caused by a lack of function of the enzyme acid alpha-1,4glucosidase [or acid maltase], which is present in lysosomes. Without the proper function of this enzyme, the glycogen that comes into the lysosomes is not broken down, but continuously accumulates and disrupts the normal functions of the cell. In muscle tissue, these enlarged lysosomes eventually cause the cells to become dysfunctional and die. When muscle cells are injured, their contents spill into the blood. GSD Type II is a muscle disease that progressively affects skeletal muscle, primarily limb girdle muscles, and muscles involved in respiration. There are three forms of Type II glycogen storage disease. The most common is the infantile form.

Infantile-onset form or Type IIa: in this type infants usually present during early infancy with weakness and flabbiness, are unable to hold up their heads and cannot do other motor tasks common for their age. HEAD - HOLD - up head, unable to hold abrot.;1 cupr.;1 abrot.;1 gels.;3 aeth.;2 glon.;1 ant-t.;1 hipp.;1 atro.;1 lil-t.;1 bapt.;1 lyc.;1 bar-m.;1 mag-c.;1 calc-p.;2 mang.;2 carb-v.;1 mez.;1 cham.;1 nux-m.;1 con.;1 nux-v.;1 croc.;1 olnd.;1

op.;2 petr.;1 phel.;1 puls.;2 rhus-t.;1 sabad.;1 sil.;2 tab.;1 verat.;2 zinc.;1

The muscles do not appear wasted. Limb girdle muscles and the muscles involved in respiration are affected. The heart muscle thickens and progressively fails in its pumping function. The patients usually die before 12 months of age due to heart failure and respiratory weakness. CHEST - HYPERTROPHY - Heart; of acon.;3 cimic.;1 aethyl-n.;1 crat.;1 aethyl-n.;1 crat.;1 aml-ns.;2 crat.;1 arn.;2 dig.;2 ars.;2 ferr.;2 aspar.;1 glon.;2 aur.;3 graph.;2 aur-i.;3 hep.;2 aur-i.;3 iber.;2 aur-m.;2 iod.;2 brom.;2 iod.;2 brom.;2 kali-bi.;1 cact.;3 kali-c.;3 cact.;3 kalm.;3 chlol.;1 lach.;2 chlol.;1 lith-c.;3 RESPIRATION - ARRESTED acet-ac.;1 alum.;1 anac.;1 ang.;1 apis;1 arn.;1 ars.;1

bar-c.;1 bell.;1 borx.;1 bry.;3 cact.;2 calc.;2 calc-p.;2

lyc.;2 lycps-v.;2 naja;2 nat-m.;2 nux-v.;1 phos.;2 phyt.;1 plb.;1 prun-v.;1 puls.;2 rhus-t.;2 spig.;2 spong.;3 spong.;3 staph.;1

camph.;2 cann-s.;1 caps.;1 carb-an.;1 carb-v.;1 carbn-s.;1 castm.;1

caust.;2 chin.;1 cic.;2 cina;2 cocc.;1 con.;1 crot-c.;1 cupr.;3 dios.;1 euphr.;1 guaj.;1 hydr-ac.;1 ign.;2 iod.;1 kali-c.;1 kali-i.;1 kalm.;1 lach.;2

lat-m.;2 led.;2 lyc.;2 lyss.;1 merc.;1 merc-c.;1 mosch.;2 naja;1 nat-m.;1 nat-s.;1 nit-ac.;1 nux-m.;2 nux-v.;1 oena.;1 op.;3 phos.;2 plat.;1 plb.;1

puls.;2 ruta;2 samb.;3 sars.;1 sep.;1 sil.;2 stann.;1 stram.;1 sulph.;2 tab.;1 tanac.;1 ter.;1 thea;1 ther.;1 verat.;2 verb.;1

Childhood-onset form or Type IIb: With this form, the disease has a later onset, in infancy or early childhood, and progresses more slowly than the infantile form. Organ involvement varies among the individual patients but muscle weakness is generally seen. The life expectancy is better than for the infantile form. GENERALS - ATROPHY ars.;1 ars.;1 bar-c.;1 bar-c.;1 calc-sil.;1 cetr.;1 chin.;1

cupr.;1 hep.;1 iod.;2 kali-c.;1 kali-p.;1 nat-m.;2 nux-v.;1

GENERALS - PARALYSIS - atrophy, with cupr.2 kali-p.1 graph.1 plb.2

phos.;1 plb.;1 plb-i.;1 plb-xyz.;1 sabal;1 sec.;1 stann.;1 sec.1 sep.1

Adult-onset form, Type IIc: Patients with this form of Type II GSD do not usually show signs of organ enlargement, but are marked by muscular weakness mimicking other chronic muscle diseases. Problems with walking are seen, due to weakness of the hip muscles. Some patients have presented with pulmonary (lung) insufficiency due to muscle weakness, and night time breathing is affected. The involvement of the muscle weakness progresses slowly over the years. Heart involvement does not appear to be a significant feature. GENERALS - FATTY DEGENERATION - organs ars.;2 cupr.;2 aur.1 kali-c.;1 calc-ar.1 lac-d.1

phos. vanad.;1

Diagnosis of Type II GSD is done by determining the activity of the enzyme alpha glucosidase. This deficiency can be shown with a muscle biopsy or cultured cells from a skin biopsy. Biopsied tissues show a great increase of glycogen of normal structure, and microscopic studies show increased glycogen enclosed within the lysosomes. Treatments for adults and children with Pompe disease is aimed at relieving stress on the muscles. A protein-rich diet is used, along with an intensive daily exercise program. Older patients, in particular, must have intension to prevent pulmonary infections. CHEST - INFLAMMATION - Lungs acon.;3 camph.;1 acon.;3 cann-s.;2 aesc.;1 cann-s.;2 agar.;2 canth.;1 all-c.;2 caps.;1 all-c.;2 carb-ac.;1 am-c.;1 carb-ac.;1 am-m.;1 carb-an.;2 ant-ar.;1 carb-v.;3 ant-c.;2 carbn-s.;2 ant-i.;1 chel.;3 ant-i.;1 chel.;3 ant-t.;3 chin.;2 ant-t.;3 chin-b.;1 apis;2 chin-b. arg-n.;2 chlor.;2 arn.;2 con.;2 ars.;3 cop.;1 ars.;3 corn.;1 ars-i.;2 corn-f.;1 ars-i.;2 crot-h.;1 ars-s-f.;1 cupr.;2 arum-t.;1 cupr.;2 aur-m.;1 dig.;2 bad.;2 dulc.;1 bar-c.;1 elaps;2 bar-i.;12 elaps;2 bell.;2 eup-per.;1 bell.;2 ferr.;2 benz-ac.;2 ferr-ar.;2 brom.;2 ferr-i.;2 bry.;3 ferr-i.;2 bry.;3 ferr-p.;3 cact.;2 ferr-p.;3 cact.;2 gels.;2 calc.;2 hep.;3 calc-s.;1 hep.;3 calc-s.;1 hippoz.;2 calc-sil.;1 hyos.;2

hyos.;2 iod.;2 ip.;2 kali-ar.;1 kali-bi.;2 kali-br.;2 kali-c.;2 kali-chl.;2 kali-i.;2 kali-m.;1 kali-n.;2 kali-n.;2 kali-p.;2 kali-p.;2 kali-s.;2 kreos.;2 lach.;2 lach.;2 lachn.;2 laur.;2 lob.;3 lyc.;3 lyc.;3 lycps-v.;1 meli-xyz.;1 merc.;3 mill.;2 myrt-c.;1 nat-ar.;12 nat-m.;2 nat-s.;2 nit-ac.;2 nux-v.;1 ol-j.;1 op.;1 ph-ac.;2 phos.;3 phos.;3 podo.;1

podo.;1 psor.;2 puls.;3 pyrog.;1 ran-b.;1 rhus-t.;3 rhus-t.;3 rumx.;1 sabad.;2 sang.;2 sec.;12

seneg.;3 seneg.;3 sep.;3 sil.;2 spig.;1 spong.;1 squil.;2 squil.;2 stram.;2 sul-ac.;1 sul-i.;12

sulph.;3 sulph.;3 sumb.;1 ter.;2 tub.;1 tub.;1 verat.;2 verat.;2 verat-v.;3 verat-v.;3

Glycogen Storage Disease Type III (GSD Type III) Synonyms: Limit Dextrinosis Debrancher Deficiency Cori Disease Forbes Disease In this glycogen storage disease, the enzyme deficiency causes the body to form glycogen molecules that have an abnormal structure. This abnormal structure also prevents the glycogen from being broken down into free glucose. There have been observed a variety of subtypes of this disorder, and there appears to be considerable variation in the tissues affected by the defect viz.such as white blood cells, muscle, liver, and so forth. In GSD Type IIIa, the disease involves both liver and muscle tissues. In Type IIIb only the liver is involved. ABDOMEN - LIVER and region of liver; complaints of abies-c.;1 aur-i.;1 abrot.;1 aur-m.;1 acon.;3 bapt.;2 aesc.;2 bar-c.;1 agar.;2 bell.;3 all-c.;1 benz-ac.;1 aloe;2 berb.;3 alum.;2 bry.;3 am-m.;2 bufo;3 ant-t.;1 cadm-s.;1 apoc.;2 calc.;3 arg-n.;2 calc-f.;2 arn.;2 calc-p.;3 ars.;2 calc-sil.;1 ars-i.;1 camph.;1 asaf.;1 carb-v.;2 aur.;2 carbn-s.;3 aur-ar.;1 card-m.;3

cham.;2 chel.;3 chin.;2 chrystl.;1 cimx.;2 cinnb.;1 clem.;1 cocc.;2 colch.;2 coll.;2 coloc.;2 combr-r.;1 con.;2 corn.;3 croc.;2 crot-c.;2 crot-h.;2 cupr.;2

dig.;1 dros.;1 dulc.;1 ferr.;1 ferr-ar.;1 ferr-p.;1 fl-ac.;2 gels.;1 graph.;2 grin.;1 haru-ma.;1 hep.;2 hydr.;2 hypoes-t.;1 iod.;3 iris;2 kali-bi.;2 kali-c.;3 kali-i.;1 kali-s.;1 lac-d.;1 lach.;3 laur.;2

lept.;3 lyc.;3 mag-c.;1 mag-m.;3 mang.;1 merc.;3 merc-c.;1 microg-p.;1 mur-ac.;1 nat-ar.;1 nat-c.;1 nat-m.;2 nat-p.;12 nat-s.;3 nit-ac.;3 nux-m.;3 nux-v.;3 oci-su.;1 petr.;1 ph-ac.;2 phos.;3 plat.;1 plb.;2

podo.;3 prun.;2 psor.;2 puls.;1 ran-b.;1 ran-s.;1 rhus-t.;1 ruta;1 sabad.;1 sang.;2 sel.;1 sep.;3 sil.;1 spig.;1 sul-ac.;1 sul-i.;1 sulph.;3 tab.;1 ther.;1 verat.;1 zinc.;2

Children with GSD III are often first diagnosed because they have been noticed to have a swollen abdomen due to a very large liver. Some children have problems with low blood sugars on fasting but this is not as common as in GSD I. Growth may be delayed during childhood but most reach a normal adult height. Muscle weakness is commonly present in childhood and can, at times, be severe. Often the liver returns to a normal size at puberty, although the enzyme defect persists. ABDOMEN - ENLARGED - Liver aconin.;1 agar.;1 anis.;1 ant-t.;1 ars.;2 ars-i.;1 aur.;1 aur-ar.;1 aur-i.;1 aur-m.;2 aur-s.;1 bar-m.;1 boerh-d.;1 bry.;2 bufo;1 calc.;2 calc-ar.;2

calc-sil.;1 carb-v.;2 carc.;1;fb card-m.;1 chel.;2 chin.;3 chinin-ar.;1 chion.;2 cocc.;2 con.;2 con.;2 dig.;2 dig.;2 eup-per.;1 ferr.;2 ferr-ar.;1 ferr-i.;1

ferr-i.;1 ferr-p.;1 fl-ac.;2 hep.;2 hippoz.;2 hippoz.;2 hydr.;1 iod.;2 kali-c.;2 kali-s.;1 lach.;1 lact.;1 laur.;2 luf-b.;1 lyc.;3 mag-m.;3 merc.;2

merc-i-r.;1 mur-ac.;1 nat-m.;2 nat-s.;3 nat-s.;3 nit-ac.;2 nux-m.;2 nux-v.;3 phos.;2 pin-s.;1

plb.;1 podo.;2 pop-c.;1 ptel.;1 sec.;1 sec.;1 sel.;1 sep.;1 sil.;1 sul-i.;1

sulph.;2 tab.;1 thuj.;1 thuj.;1 tub.;2 urt-u.;1 vip.;1 zinc.;2 zinc-p.;1

Chemical analysis of the blood usually shows low blood sugar, elevated glycogen content in red blood cells, and elevated levels of fat. Uric acid and lactic acid levels are usually normal. Biopsy of the liver shows inflammatory changes, with great elevations of abnormal-structured glycogen content, and a deficiency of the debrancher enzyme. Biopsy of muscle shows an accumulation of abnormal-structured glycogen in Type IIIa. Treatment for Type III glycogen storage disease consists of frequent feedings and a high protein diet. Continuous nasogastric feedings and the starch regimes similar to those used for Type I GSD are useful. Persons with debrancher deficiency have lived well into late adulthood. Muscle disorders seem to be an increasing problem with age in those persons with Type IIIa. The heart can be mildly enlarged, but the function is usually normal.

Glycogen Storage Disease Type IV (GSD Type IV) Synonyms: Amylopectinosis Brancher Deficiency Andersen Disease In this type, there is not an increased amount of glycogen in the tissues, as in other forms of GSD. Instead, the glycogen that does accumulate has very long outer branches, because there is a genetic deficiency of the branching enzyme. This structural abnormality of the glycogen is thought to trigger the body's immune system, causing the body to actually attack the glycogen and the tissues in which it is stored. The result is tremendous scarring (cirrhosis) of the liver as well as other organs, such as muscle. The typical symptomatology of this disease is the result of the scarring process. ABDOMEN - CIRRHOSIS of liver boerh-d.;1 cas-s.;1 calc-ar.;1 chin.;1 card-m.;2 cupr.;2 card-m.;2 cupr.;2 card-m.1 cupr.;2;

diosm.;1 dulc.;1 hep.;2 hep.;2 hydr.;2

hydr.;2 mur-ac.;2 mur-ac.;2

phos.;2 phos.;2 plb.;1

sulph.;2 sulph.;2 urea;1

A baby with the typical Type IV GSD appears to be normal at birth. The first indication of a problem is a failure to thrive. The rate of growth and mental progress of the baby stops at a certain point and does not continue normally. The liver and spleen enlarge, there is little weight gain, and muscles develop poor tone. The course of the disease is one of progressive cirrhosis and associated problems. Death typically occurs by five years of age. ABDOMEN - ENLARGED - Spleen aconin.;1 dros.;1 agn.;1 ferr.;2 anthraci.;2 ferr-ar.;1 aran.;2 ferr-ar.;1 ars.;2 ferr-i.;1 ars-i.;2 ferr-i.;1 ars-s-f.;1 ferr-m.;2 aur-m.;2 ferr-m.;2 aur-m.;2 ferr-p.;1 calc.;2 grin.;1 calc-i.;1 hippoz.;2 caps.;2 hydr.;1 carb-v.;1 ign.;2 cean.;3 iod.;3 chin.;3 kali-m.;12 chinin-ar.;1 lach.;2 chinin-s.;2 laur.;1 chinin-s.;2 mag-m.;1 cit-v.;2 mag-m.;1 cocc.;2 merc-i-r.;1 con.;2 merc-i-r.;1 GENERALS - OBESITY - children, in ant-c.1 calc.;3 bad.2 calc.;3 bar-c.;1 caps.;2 calc.;3 ferr.;2 calc.;3 kali-bi.;2 GENERALS - DEVELOPMENT, arrested agar.;1 calc-p.;3 bac.;1 caust.;1 bar-c.;2 chin.;1 bar-c.;2 cupr.;1 borx.;1 cupr.;1 borx.;1 des-ac.;1 bufo;1 des-ac.;1 calc.;2 kali-c.;1

nat-m.;2 nat-m.;2 nit-ac.;2 nux-m.;1 nux-v.;2 op.;2 ph-ac.;2 phos.;2 phos.;2 plb.;1 plb-i.;1 ran-s.;2 ruta;1 sul-ac.;2 sul-i.;1 sulph.;2 tab.;1 urt-u.;2 xanrhi.;1

kali-bi. sacch.;1 seneg.;1

kreos.;1 lac-d.;1 med.;1 nat-m.;1 nat-m.;1 nep.;1 nep.;1 ph-ac.;1

phos.;2 pin-s.;1 sil.;2

sulfa.;1 sulfa.;1 sulph.;1

GENERALS - RELAXATION - muscles; of acet-ac.;1 crot-c.;2 aeth.;1 cupr.;1 agar.;2 cur.;1 alum.;1 cycl.;1 ambr.;1 dig.;1 amyg. dios.;2 ang.;1 dros.;1 anh.;1;mg1 euph.;1 ant-t.;1 ferr.;2 arg-met.;1 ferr-ar.;1 arn.;1 ferr-i.;1 ars.;2 fl-ac.;1 asaf.;1 gels.;3 atro.;1 glor-si.;1 bar-m.;1 glor-su.;1 bar-s.;1 graph.;2 bell. guare.;1 borx.;1 hell.;2 bry.;1 helo.;1 calc.;3 hep.;1 calc-sil.;1 hydr.;1 camph.;1 hydr-ac.;1 canth.;1 hydrog.;1 caps.;3 hyos.;2 carb-ac.;1 iod.;2 carb-an.;1 ip.;2 carbn-o.;1 jug-r.;1 carbn-s.;1 kali-ar.;1 caust.;1 kali-c.;3 caust.;12 kali-m.;1 cham.;2 kali-n.;1 chin.;1 kali-p.;1 chinin-ar.;1 kali-s.;1 chlor.;1 lach.;1 cic.;1 laur.;1 clem.;2 lyc.;2 coca;1 mag-c.;2 cocc.;3 mang.;1 colch.;1 merc.;1 con.;2 morph.;1 croc.;2 mur-ac.;1

thyr.;1 vip.;1 vip.;1 murx.;1 nat-c.;1 nat-p.;1 nat-p.;1 nit-ac.;1 nux-m.;1 nux-v.;1 olnd.;1 op.;1 oxyt.;1 ph-ac.;1 phos.;3 phys.;1 plat.;1 plb.;1 puls.;1 rheum;1 sabad.;1 sec.;2 seneg.;2 sep.;2 sil.;1 sol-ni.;1 spig.;1 spong.;2 stram.;1 sul-ac.;1 sul-h.;1 sulph.;2 tab.;1 tab.;1 ter.;1 thuj.;1 tril-p.;1 verat.;2 verat.;2 verat.;2 verat.;2 verat-v.;1 viol-o.;1 zinc.;1

There have been a few older patients seen with severe muscle problems, who are found to have abnormal glycogen of the type associated with this type of glycogen storage disease.

Treatment for Type IV glycogen storage disease has been aimed at the failing liver, which has been symptomatic. Several patients have had liver transplants; however after transplantation, muscle and heart disease may still be a problem.

Glycogen Storage Disease Type V (GSD Type V) Synonyms: Myophosphorylase Deficiency Muscle Phosphorylase Deficiency McArdle Disease The phosphorylase enzyme plays a vital role in the breakdown of glycogen into glucose. In the absence of phosphorylase in muscles, glucose can not be released from the glycogen stored in skeletal muscles to create energy. People with Type V GSD experience problems performing and completing most exercises, especially anaerobic exercises. Because they lack the enzyme to metabolize glycogen, which is the main source of energy for anaerobic activity, their body struggles to find other sources of energy to complete a given activity or exercise. Under these circumstances, the body breaks down muscle when trying to attain energy. This causes many symptoms such as muscle pain, muscle cramping, muscle fatigue, and muscle tenderness. With the breakdown of muscle (rhabdomyolysis) and the release of the red protein myoglobin, myoglobinuria may develop, as evidenced by dark-red or red-brown urine. Serum creatine kinase levels will be greatly elevated. GENERALS - WEAKNESS - muscular acon.;1 cann-s.;1 agar.;1 canth.;1 alum.;1 carb-ac.;2 alumn.;1 carb-v.;2 alumn.;1 caust.;1 am-c.;1 cham.;1 am-m.;1 chin.;2 anac.;1 chlol.;2 ant-c.;1 chlol.1 arn.;1 cimic.;1 arn.;1 cocc.;1 ars.;1 cocc.;1 asaf.;1 colch.;1 aur.;1 con.;2 bar-c.;3 cortico.;1 bar-m.;1 cortico.;1 bar-m. croc.;2 bell.;1 dig.;2 berb.;1 dros.;1 bry.;1 dulc.;2 calc.;2 euphr.;1 calc. ferr.;2

ferr-m.;1 ferr-m. ferr-p.;1 gels.;3 gels. graph.;1 hyos.;1 iod.;1 kali-bi.;1 kali-c.;1 kali-n.;1 kali-p.;2 laur.;1 lyc.;2 macro.;1 macro.;1 macro.;1 mag-c.;1 mag-m.;1 mag-p.;1 mang.;1 meny.;1

merc.;1 mez.;1 mur-ac.;1 mur-ac.;1 nat-c.;2 nat-m.;3 nat-m.;3 nit-ac.;3 nux-v.;1 olnd.;1 op.;2 op. petr.;1 ph-ac.;1 ph-ac.;12 phos.;1 phys.;1 phys.;1

pic-ac.;3 pic-ac.;3 pic-ac.2 plat.;2 plb.;2 plb. plb.;21 puls.;1 rad-br.;1 rheum;1 rhod.;2 sabad.;1 sabad.;1 sabad.;1 sarcol-ac.;1 sarcol-ac.;1 sec.;1 sep.;2

GENERALS - PAIN - Muscles, of achy.;1 eryt-j.;1 achy.;1 ferr-p.;1 acon.;2 ferr-p.;1 agav-t.;1 form.;1 agav-t.;1 form.;1 alet.;1 gels.;2 am-caust.;1 gels.;2 am-caust.;1 harp.;1 ant-t.;2 harp.;1 arn.;2 hist.;1 arn.;21 hist.;1 ars.;1 ign.;1 aster.;1 ign.;1 aster.;1 lat-m.;1 bell.;1 lat-m.;1 bell-p.;1 led.;1 bell-p.;1 lyc.;1 brach.;1 lyc.;1 brach.;1 macro.;2 bry.;2 mag-s.;1 bry.;21 mag-s.;1 carbn-s.;1 mag-s.;1 caust.;2 mand.;1 caust.;2 mand.;1 cimic.;2 mand.;1 colch.;2 merc.;1 colch.;2 merc-c.;1 dulc.;2 merc-c.;1 dulc.;21 morph.;1 eryt-j.;1 nat-f.;1

sil.;2 sin-n.;1 sin-n. spig.;1 stann.;1 stram.;1 stront-c.;1 sul-ac.;1 sulph.;2 ter.;1 ter. thuj.;1 verat.;2 verat. verat-v.;1 zinc.;1

nat-f.;1 nat-f.;1 nat-m.;1 nat-m.;1 nat-m.;1 op.;1 op.;1 phyt.;2 phyt.;2 plb.;1 plb.;1 puls.;1 puls.;1 ran-b.;2 rauw.;1 rauw.;1 rham-cal.;1 rham-cath.;1 rhus-t.;2 rhus-t.;21 ruta;2 sal-ac.;1 sil.;1 sil.;11 staph.;1 staph.;11 stram.;1 stroph-s.;1 stroph-s.;1 stry.;2

stry.;2 sulfa.;1 sulfa.;1 tab.;1 tab.;1 tarax.;1 tarax.;1

thal.;1 thal.;1 thal.;11 thuj.;1 thuj.;1 valer.;1 verat.;2

verat.;2 verat.;2 verat-v.;2 zinc.;1 zinc.;1

GENERALS - DEGENERATION of tissues, tendency to arn.;1 GENERALS - PAIN - cramping - muscles, in acon.;1 cimic.;1 agar.;1 cimic.;1 alum.;1 cina;3 am-c.;1 clem.;1 am-m.;1 cocc.;2 ambr.;2 cocc. anac.;3 colch.;1 anac. coloc.;3 ang.;3 coloc. arg-met.;1 con.;2 arn.;2 conin.;1 ars.;2 conin.;1 asaf.;1 croc.;1 asar.;1 cupr.;3 asar.;1 cupr. aur.;1 cupr-act.;2 bar-c.;1 cupr-act. bell.;3 cyt-l.;1 bell.;32 cyt-l.;1 bism.;1 dig.;1 bov.;1 dios.;2 bry.;1 dios. bufo;1 dros.;1 calc.;3 dulc.;2 camph.;1 euph.;1 camph. euphr.;2 cann-s.;2 ferr.;1 caps.;1 gels.;1 carb-an.;1 gels. carb-v.;1 graph.;2 carbn-s.;1 graph. carbn-s.;1 haliae-lc.;1 castm. hell.;1 caust.;2 hep.;1 caust. hist.;1 cham.;2 hist.;1 chin.;1 hyos.;1 cic.;1 ign.

ign.;2 iod.;1 ip.;1 iris kali-br. kali-br.;2 kali-c.;2 kali-n.;1 kreos.;1 lach.;1 lat-m.;1 lat-m.;1 lyc.;3 mag-c.;1 mag-m.;1 mag-p.;2 mag-p.;2 mang.;1 meny.;1 merc.;3 mez.;1 morph.;1 morph.;1 mosch.;1 mur-ac.;2 nat-c.;1 nat-f.;1 nat-f.;1 nat-m.;1 nit-ac.;2 nux-m.;1 nux-v. nux-v.;3 olnd.;1 op. op.;21 op.;2 petr.;2

ph-ac.;1 phos.;1 phyt.;12 phyt.;11 phyt.;1 plat.;3 plb.;2 plb. plb.;2 puls.;1 puls.;1 ran-b.;1 rheum;1 rhod.;1 rhus-t.;2

ruta;1 sabad.;1 samb.;1 sang.;1 sarcol-ac.;1 sarcol-ac.;1 sec.;2 sep.;3 sil.;3 spig.;2 spong.;2 squil.;1 stann.;2 staph.;1 stram.;1

stront-c.;1 sul-ac.;3 sulph.;3 tab.;2 tab.;2 tab.;2 thuj.;2 valer.;2 verat.;3 verb.;2 viol-o.;1 viol-t.;1 zinc.;1 zinc.

The physical exam of patients with Type V glycogen storage is normal. They complain of painful muscle cramps after exercise. These persons are commonly muscular; they do not have large livers, and are normal in height. Their liver phophorylase activity is normal, and they do not have hypoglycemia. A muscle biopsy will show increased concentrations of glycogen, and a deficiency of the phosphorylase enzyme. At present, there is no specific treatment for this type of GSD. It is very important for patients to exercise only moderately, for extensive exercise can cause considerable muscle breakdown resulting in a great deal of myoglobin in the urine. Large amounts of myoglobin may precipitate in the kidneys and cause temporary kidney failure. Some patients have developed significant muscle problems (myopathies) later in life.

Glycogen Storage Disease Type VI (GSD Type VI) Synonyms: Hers Disease Liver Phosphorylase Deficiency The phosphorylase enzyme plays a vital role in the breakdown of glycogen into glucose. With a deficiency of the liver phosphorylase enzyme, glycogen cannot be broken down to glucose, and the accumulating glycogen results in an enlarged liver. A total deficiency of this liver enzyme would not likely be compatible with life, thus patients with Type VI GSD actually have only partial deficiency of the enzyme. This form of glycogen storage disease appears to be similar to, but is usually considerably milder than glucose-6-phosphatase deficiency GSD (type I GSD). Extreme enlargement of the liver, growth retardation, and mild hypoglycemia are seen, but patients can certainly present with few symptoms and be able to lead normal lives. The diagnosis of this disease is based on liver biopsy material; assays must be done for glycogen content (which is increased) as well as for phosphorylase activity. Phosphorylase activity in the liver tissue is present but reduced.

Due to the mildness of the clinical findings, treatment is usually not required. Should hypoglycemia and growth failure be a major problem, these patients should receive the same nutritional management that has been effective in Type I GSD and Type III GSD.

Glycogen Storage Disease Type VII (GSD Type VII) Synonyms: Muscle Phosphofructokinase Deficiency Tarui Disease The phosphofructokinase enzyme is needed to facilitate the breakdown of glycogen into energy in muscle. Patients with this type of GSD have a deficient amount of this enzyme in their muscle tissue. With this deficiency, effective glycogen breakdown (glycolysis) during muscle stress cannot be accomplished, resulting in pain, weakness, and cramping in the exercising muscle. The clinical features of Type VII Glycogen Storage Disease are similar to those of Type V GSD. Patients experience early onset of fatigue and muscle pain with exercise. The body breaks down muscle when trying to attain energy, which causes many symptoms such as muscle pain, muscle cramping, muscle fatigue, and muscle tenderness. With the breakdown of muscle (rhabdomyolysis) and the release of the red protein myoglobin, myoglobinuria may develop, as evidenced by dark-red or redbrown urine. However, exercise intolerance is evident in childhood and symptoms are more severe than in Type V GSD. Diagnosis of Type VII Glycogen Storage Disease is done by muscle biopsy, with a deficiency of the muscle phosphofructokinase enzyme and a modest accumulation of glycogen found. Patients may also display a hemolytic anemia.

Glycogen Storage Disease Type IX (GSD Type IX) Synonyms: Phosphorylase Kinase Deficiency Patients with this type of glycogen storage disease have a deficiency of the phosphorylase kinase enzyme. The phosphorylase kinase enzyme is a regulatory enzyme in the breakdown of glycogen, thus the deficiency of this enzyme results in glycogen accumulation. The clinical picture of Type IX glycogen storage disease is similar to that seen in Type VI GSD, liver phosphorlyase deficiency. The most common symptoms are enlarged liver, growth retardation, mild delay in motor development, and elevated blood lipids. All of the symptoms usually improve as the child ages, and most adults are of normal height.

Phosphorylase kinase is a complex enzyme. Several subtypes of phophorylase kinase deficiency have been identified, based on which tissues the enzyme deficiency occurs, and the type of inheritance. The inheritance of Type IX glycogen storage disease can be autosomal recessive, or X-linked recessive. The most common form of Type IX GSD is the X-linked form, which accounts for nearly 75% of all cases. Definitive diagnosis of Type IX GSD requires a liver biopsy.

Glycogen Storage Disease Type 0 (GSD Type 0) Synonyms: Hepatic Glycogen Synthase Deficiency Type 0 glycogen storage disease (GSD 0) is caused by a deficiency in glycogen synthase, an enzyme critical for adequate glycogen synthesis. As a result, there is a marked decrease in glycogen stores resulting in fasting hypoglycemia and postprandial hyperglycemia. Dietary carbohydrates are preferentially converted to lactate. In patients with Type 0 Glycogen Storage Disease, fasting ketotic hypoglycemia develops upon cessation of night time feedings. Early in infancy, children are usually asymptomatic, but weaning from overnight feeds is difficult. During gastrointestinal illness or periods of poor enteral intake, children may become lethargic and usually the hypoglycemia is an incidental finding. Growth throughout childhood may be mildly delayed, but most children remain developmentally normal. Fatigue with exertion is common, and the aforementioned lactic acid accumulation with carbohydrate intake may contribute to muscle cramps. The physical exam is usually normal with no hepatomegaly. Glucosuria and ketonuria are common in the morning after breakfast, and may lead to confusion regarding early diabetes. Diagnosis of Type 0 Glycogen Storage Disease should be considered in any child with ketotic hypoglycemia who has a history of needing frequent meals or snacks. Monitoring will reveal a unique metabolic disturbance characterized by alternating fasting hypoglycemia and hyperketonemia followed by hyperglycemia and hyperlacticacidemia with feeding. A liver biopsy shows hepatocytes that contain only small amounts of glycogen with moderate steatosis. Mutation analysis likely will replace liver biopsies in the near future as the gold standard for confirmation of the diagnosis. The goal of treatment for Type 0 GSD is to prevent hypoglycemia by avoiding fasting. Frequent meals and snacks can be given every 3-4 hours during the day. Uncooked cornstarch (2 grams/kg) will prevent hypoglycemia overnight. As carbohydrates are preferentially shunted to lactic acid, a diet with increased amounts of protein is recommended. GENERALS - FASTING - agg. acon.;1 alum.;1 aloe;1 alum.;1 aloe;1 am-c.;1

am-c.;1 am-m.;2 am-m.;2

ambr.;2 ambr.;2 anac.;1 anac.;1 ars.;1 ars.;1 bar-c.;2 bar-c.;2 bar-i.;1 bov.;1 brass-n-o.;1 bry.;2 cact.;1 calc.;3 calc.;3 calc-i.;1 cann-i.;1 cann-s.;1 canth.;1 carb-ac.;2 carb-ac.;2 carb-an.;2 carb-an.;2 carb-v.;1 carb-v.;1 castm.;1 caust.;1 caust.;1 chel.;2 chel.;2 chin.;1 chin.;1 cina;1 cina;1 coc-c.;2 coc-c.;2 croc.;3 croc.;3 dios.;1 dios.;1 ferr.;1

ferr.;1 ferr-p.;1 ferr-p.;1 gran.;1 graph.;2 graph.;2 hell.;1 hell.;1 hep.;2 hep.;2 ign.;2 ign.;2 iod.;3 iod.;3 kali-c.;2 kali-c.;2 kreos.;1 kreos.;1 lach.;3 lach.;3 laur.;1 laur.;1 lyc.;1 lyc.;1 mag-c.;1 mag-c.;1 mag-m.;1 mag-m.;1 merc.;1 merc.;1 mez.;2 mez.;2 nat-c.;1 nat-c.;1 nat-p.;12 nit-ac.;1 nit-ac.;1 nux-v.;2 nux-v.;2 petr.;1 petr.;1

GENERALS - DIABETES MELLITUS brid-fr.;1 op.;2 morind-l.;1 orthos-s.;1 morind-m.;1 phlor.;1 nauc-l.;1 uran-m.;1

phos.;2 phos.;2 plat.;3 plat.;3 plb.;3 plb.;3 psor.;2 puls.;1 puls.;1 ran-b.;3 ran-b.;3 ran-s.;1 rhod.;1 rhus-t.;1 rumx.;2 rumx.;2 sabad.;2 sabad.;2 sep.;3 sep.;3 spig.;2 spig.;2 staph.;3 staph.;3 stront-c.;1 sulph.;2 sulph.;2 tab.;3 tab.;3 tarax.;2 tarax.;2 teucr.;1 teucr.;1 valer.;2 valer.;2 verat.;1 verat.;1 verb.;2 verb.;2

uran-n.;2 vinc-r.;1

Type 0 Glycogen Storage Disease is inherited in an autosomal recessive manner, and is due to mutations in the GYS2 gene which is located on chromosome 12p12.2.

While only 15 cases have been described as there is evidence that this disease is under diagnosed; prevalence estimates, however, have not been made. Type 0 GSD affects both genders and cases.