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Glycogen storage disease IXc(GSD9C)

MedGen UID:
442778
Concept ID:
C2751643
Disease or Syndrome
Synonyms: GSD IXc; GSD9C; PHKG2-Related Phosphorylase Kinase Deficiency
 
Gene (location): PHKG2 (16p11.2)
 
Monarch Initiative: MONDO:0013091
OMIM®: 613027

Disease characteristics

Excerpted from the GeneReview: Phosphorylase Kinase Deficiency
Phosphorylase kinase (PhK) deficiency causing glycogen storage disease type IX (GSD IX) results from deficiency of the enzyme phosphorylase b kinase, which has a major regulatory role in the breakdown of glycogen. The two types of PhK deficiency are liver PhK deficiency (characterized by early childhood onset of hepatomegaly and growth restriction, and often, but not always, fasting ketosis and hypoglycemia) and muscle PhK deficiency, which is considerably rarer (characterized by any of the following: exercise intolerance, myalgia, muscle cramps, myoglobinuria, and progressive muscle weakness). While symptoms and biochemical abnormalities of liver PhK deficiency were thought to improve with age, it is becoming evident that affected individuals need to be monitored for long-term complications such as liver fibrosis and cirrhosis. [from GeneReviews]
Authors:
Mrudu Herbert  |  Jennifer L Goldstein  |  Catherine Rehder, et. al.   view full author information

Additional descriptions

From OMIM
Glycogen storage disease IXc (GSD9C) is characterized by onset in childhood of hepatomegaly, hypotonia, growth retardation in childhood, and liver dysfunction. These symptoms improve with age in most cases; however, some patients may develop hepatic fibrosis or cirrhosis (Burwinkel et al., 1998). For a general description and a discussion of genetic heterogeneity of GSD IX, see GSD9A (306000).  http://www.omim.org/entry/613027
From MedlinePlus Genetics
Glycogen storage disease type IX (also known as GSD IX) is a condition caused by the inability to break down a complex sugar called glycogen. The different forms of the condition can affect glycogen breakdown in liver cells or muscle cells or sometimes both. A lack of glycogen breakdown interferes with the normal function of the affected tissue.

When GSD IX affects the liver, the signs and symptoms typically begin in early childhood. The initial features are usually an enlarged liver (hepatomegaly) and slow growth. Affected children are often shorter than normal. During prolonged periods without food (fasting), affected individuals may have low blood sugar (hypoglycemia) or elevated levels of ketones in the blood (ketosis). Ketones are molecules produced during the breakdown of fats, which occurs when stored sugars are unavailable. Affected children may have delayed development of motor skills, such as sitting, standing, or walking, and some have mild muscle weakness. Puberty is delayed in some adolescents with GSD IX. In the form of the condition that affects the liver, the signs and symptoms usually improve with age. Typically, individuals catch up developmentally, and adults reach normal height. However, some affected individuals have a buildup of scar tissue (fibrosis) in the liver, which can rarely progress to irreversible liver disease (cirrhosis).

GSD IX can affect muscle tissue, although this form of the condition is very rare and not well understood. The features of this form of the condition can appear anytime from childhood to adulthood. Affected individuals may experience fatigue, muscle pain, and cramps, especially during exercise (exercise intolerance). Most affected individuals have muscle weakness that worsens over time. GSD IX can cause myoglobinuria, which occurs when muscle tissue breaks down abnormally and releases a protein called myoglobin that is excreted in the urine. Myoglobinuria can cause the urine to be red or brown.

In a small number of people with GSD IX, the liver and muscles are both affected. These individuals develop a combination of the features described above, although the muscle problems are usually mild.  https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-ix

Clinical features

From HPO
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Postnatal growth retardation
MedGen UID:
395343
Concept ID:
C1859778
Finding
Slow or limited growth after birth.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Cirrhosis of liver
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
Bile duct proliferation
MedGen UID:
120603
Concept ID:
C0267818
Disease or Syndrome
Proliferative changes of the bile ducts.
Increased hepatic glycogen content
MedGen UID:
344698
Concept ID:
C1856285
Finding
An increase in the amount of glycogen stored in hepatocytes compared to normal.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Ketosis
MedGen UID:
7206
Concept ID:
C0022638
Disease or Syndrome
Presence of elevated levels of ketone bodies in the body.
Fasting hypoglycemia
MedGen UID:
75765
Concept ID:
C0271708
Disease or Syndrome
HYPOGLYCEMIA expressed in the postabsorptive state, after prolonged FASTING, or an overnight fast.
Hypertriglyceridemia
MedGen UID:
167238
Concept ID:
C0813230
Finding
An abnormal increase in the level of triglycerides in the blood.
Increased circulating lactate concentration
MedGen UID:
332209
Concept ID:
C1836440
Finding
Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).
Elevated circulating hepatic transaminase concentration
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Reduced hepatic phosphorylase kinase activity
MedGen UID:
1054423
Concept ID:
CN377142
Finding
Activity of phosphorylase kinase in liver tissue below the lower limit of normal. Phosphorylase kinase (PhK) has a major regulatory role in the breakdown of glycogen. The enzyme PhK comprises four copies each of four subunits, encoded by PHKA1, PHKA2, PHKB, and PHKG.

Recent clinical studies

Etiology

Degrassi I, Deheragoda M, Creegen D, Mundy H, Mustafa A, Vara R, Hadzic N
Dig Liver Dis 2021 Jan;53(1):86-93. Epub 2020 Jun 4 doi: 10.1016/j.dld.2020.04.017. PMID: 32505569

Diagnosis

Shao Y, Li T, Jiang M, Xu J, Huang Y, Li X, Zheng R, Liu L
BMC Pediatr 2022 May 12;22(1):267. doi: 10.1186/s12887-021-03055-7. PMID: 35549678Free PMC Article
Degrassi I, Deheragoda M, Creegen D, Mundy H, Mustafa A, Vara R, Hadzic N
Dig Liver Dis 2021 Jan;53(1):86-93. Epub 2020 Jun 4 doi: 10.1016/j.dld.2020.04.017. PMID: 32505569

Clinical prediction guides

Degrassi I, Deheragoda M, Creegen D, Mundy H, Mustafa A, Vara R, Hadzic N
Dig Liver Dis 2021 Jan;53(1):86-93. Epub 2020 Jun 4 doi: 10.1016/j.dld.2020.04.017. PMID: 32505569

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