Format

Send to

Choose Destination
See comment in PubMed Commons below

Phosphorylase Kinase Deficiency.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
2011 May 31.

Excerpt

CLINICAL CHARACTERISTICS:

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 retardation, 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). Symptoms and biochemical abnormalities of liver PhK deficiency are thought to improve with age.

DIAGNOSIS/TESTING:

The enzyme PhK comprises four copies each of four subunits (α, β, γ, and δ). Pathogenic variants in PHKA1, encoding subunit α, cause the rare X-linked disorder muscle PhK deficiency; pathogenic variants in PHKA2, also encoding subunit α, cause the most common form, liver PhK deficiency (X-linked liver glycogenosis); pathogenic variants in PHKB, encoding subunit β, cause autosomal recessive PhK deficiency in both liver and muscle; and pathogenic variants in PHKG2, encoding subunit γ, cause autosomal recessive liver PhK deficiency. Diagnosis is based on clinical findings, assay of PhK activity in erythrocytes, or liver or muscle tissues (depending upon presentation) and confirmatory findings on molecular genetic testing.

MANAGEMENT:

Treatment of manifestations: Liver PhK deficiency: hypoglycemia can be prevented with frequent daytime feedings that are high in complex carbohydrates and protein. When hypoglycemia or ketosis is present, Polycose® or fruit juice is given orally as tolerated or glucose by IV. Liver manifestations (e.g., cirrhosis, liver failure, portal hypertension) are managed symptomatically. Muscle PhK deficiency: Physical therapy based on physical status and function; optimization of blood glucose concentrations by a metabolic nutritionist based on activity. Prevention of primary manifestations: Liver PhK deficiency: Diet high in complex carbohydrates and protein to prevent hypoglycemia and ketosis if present. Muscle PhK deficiency: Little published information is available. Prevention of secondary complications: Liver PhK deficiency: IV glucose infusion preoperatively for elective procedures followed by intraoperative and post-operative IV glucose infusion to prevent hypoglycemia; malignant hyperthermia precautions when general anesthesia is required. Surveillance: Liver PhK deficiency: Regular evaluation by a metabolic physician and a metabolic nutritionist. Monitoring of blood glucose concentration and blood ketones routinely as well as during times of stress (e.g., illness, intense activity, rapid growth, puberty) and reduced food intake. In children younger than age 18 years, liver ultrasound examination should be performed every 12 to 24 months. With increasing age, CT or MRI using intravenous contrast should be considered to evaluate for complications of liver disease. Muscle PhK deficiency: Regular evaluation by a metabolic physician, a metabolic nutritionist, and physical therapist. Agents/circumstances to avoid: Liver PhK deficiency: Large amounts of simple sugars as they will increase liver storage of glycogen; prolonged fasting; high-impact contact sports if significant hepatomegaly is present; drugs known to cause hypoglycemia such as insulin and insulin secretogogues (the sulfonylureas); alcohol (which may predispose to hypoglycemia). Muscle PhK deficiency: Vigorous exercise; medications like succinylcholine and statins that can cause rhabdomyolysis. Evaluation of relatives at risk: Molecular genetic testing (if the family-specific pathogenic variants are known) and/or evaluation by a metabolic physician (if the family-specific pathogenic variants are not known) allow early diagnosis and treatment for sibs at increased risk for liver PhK deficiency. Pregnancy management: Dietary management to maintain euglycemia throughout pregnancy.

GENETIC COUNSELING:

PHKA2-related liver PhK deficiency and PHKA1-related muscle PhK deficiency are inherited in an X-linked manner. PHKB-related liver and muscle PhK deficiency and PHKG2-related liver PhK deficiency are inherited in an autosomal recessive manner. X-linked inheritance: If the mother is a carrier, the chance of transmitting it in each pregnancy is 50%. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers. Affected males pass the pathogenic variant to all of their daughters and none of their sons. Carrier testing for at-risk female relatives and prenatal testing for pregnancies at risk are possible if the pathogenic variant in the family has been identified. Autosomal recessive inheritance: At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at risk are possible if the pathogenic variants in the family have been identified.

Copyright © 1993-2017, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Support Center