U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Glycogen storage disease IXd(GSD9D)

MedGen UID:
335112
Concept ID:
C1845151
Disease or Syndrome
Synonyms: GSD IXd; GSD9D; Muscle Phosphorylase Kinase Deficiency; PHKA1-Related Phosphorylase Kinase Deficiency
SNOMED CT: Glycogen storage disease due to muscle phosphorylase kinase deficiency (819953000); Glycogen storage disease type 9D (819953000); Glycogen storage disease type IXd (819953000); Glycogenosis type 9D (819953000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): PHKA1 (Xq13.1)
 
Monarch Initiative: MONDO:0010362
OMIM®: 300559
Orphanet: ORPHA715

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 IXd (GSD9D) is an X-linked recessive, relatively mild metabolic disorder characterized by variable exercise-induced muscle weakness or stiffness. Most patients have adult onset of symptoms, and some remain asymptomatic even in late adulthood. The phenotype is usually only apparent with intense exercise (summary by Preisler et al., 2012). For a discussion of genetic heterogeneity of GSD IX, see GSD9A (306000).  http://www.omim.org/entry/300559
From MedlinePlus Genetics
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.

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.

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.  https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-ix

Clinical features

From HPO
Exercise intolerance
MedGen UID:
603270
Concept ID:
C0424551
Finding
A functional motor deficit where individuals whose responses to the challenges of exercise fail to achieve levels considered normal for their age and gender.
Exercise-induced myalgia
MedGen UID:
340638
Concept ID:
C1850830
Sign or Symptom
The occurrence of an unusually high amount of muscle pain following exercise.
Exercise-induced myoglobinuria
MedGen UID:
337172
Concept ID:
C1845155
Finding
Presence of myoglobin in the urine following exercise.
Pelvic girdle muscle weakness
MedGen UID:
96534
Concept ID:
C0427064
Finding
Weakness of the muscles of the pelvic girdle (also known as the hip girdle), that is, lack of strength of the muscles around the pelvis.
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Quadriceps muscle weakness
MedGen UID:
154367
Concept ID:
C0577655
Sign or Symptom
Weakness of the quadriceps muscle (that is, of the muscle fasciculus of quadriceps femoris).
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Muscle fiber necrosis
MedGen UID:
376893
Concept ID:
C1850848
Pathologic Function
Abnormal cell death involving muscle fibers usually associated with break in, or absence of, muscle surface fiber membrane and resulting in irreversible damage to muscle fibers.
Exercise-induced muscle stiffness
MedGen UID:
343388
Concept ID:
C1855579
Finding
A type of muscle stiffness that occurs following physical exertion.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Increased muscle glycogen content
MedGen UID:
409660
Concept ID:
C1968729
Finding
An increased amount of glycogen in muscle tissue.
Glycogen accumulation in muscle fiber lysosomes
MedGen UID:
868175
Concept ID:
C4022567
Finding
An increased amount of glycogen in muscle tissue found specifically in lysosomes.
Reduced muscle phosphorylase kinase activity
MedGen UID:
1053156
Concept ID:
CN376711
Finding
Activity of the enzyme muscle phosphorylase kinase (PhK) in muscle tissue below the lower limit of normal.

Recent clinical studies

Diagnosis

Picillo E, Onore ME, Passamano L, Nigro V, Politano L
Acta Myol 2024;43(1):21-26. Epub 2024 Feb 21 doi: 10.36185/2532-1900-411. PMID: 38586167Free PMC Article
Fernandes SA, Cooper GE, Gibson RA, Kishnani PS
Mol Genet Metab 2020 Nov;131(3):299-305. Epub 2020 Oct 10 doi: 10.1016/j.ymgme.2020.10.004. PMID: 33317799Free PMC Article
Li H, Xue Y, Yu J, Guo S, Liu C
Neuromuscul Disord 2020 Jul;30(7):562-565. Epub 2020 Jun 12 doi: 10.1016/j.nmd.2020.06.006. PMID: 32660786

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...