Autosomal Liver and Muscle Phosphorylase Kinase Deficiency - Causes, Symptoms, and Treatment

Introduction:

Genetic diseases are determined by a combination of genes of a particular trait. These genes are a package of the chromosome received from either father or the mother. Recessive disorders occur when an individual inherits altered genes from each parent. Individuals receive normal and abnormal genes from the carrier parent. The chances of the baby receiving normal genes from both parents are about 25 %. The chances are the same for males and females. An X-linked recessive genetic disorder is caused by an altered gene on the X-chromosome. The glycogen storage disease is caused by a mutation of the PHKA 2 gene, which is located on the short arm of the X-chromosome.

What Is Autosomal Liver and Muscle Phosphorylase Kinase Deficiency?

Autosomal liver and muscle phosphorylase kinase deficiency are also known as glycogen storage deficiency. These are large groups of disorders in which the body fails to metabolize glycogen into glucose. The underlying cause varies for each glycogen storage disease. A reported case of phosphorylase kinase deficiency of the liver with consistent autosomal recessive inheritance was more linked with X-linked inheritance. Normally glycogen is metabolized into a simple sugar known as glucose. Phosphorylase kinase is the enzyme that boosts the transformation. When this fails, excess glycogen storage gets stored in the body, mainly in the liver and muscles, and when the body requires more energy, it is then converted into glucose.

Autosomal phosphorylase kinase deficiency is mainly of two types: one that affects the liver, and the other involves muscle. This deficiency occurs due to a lack of phosphorylase b kinase, which has a major regulatory role in the breakdown of glycogen. Liver phosphorylase kinase deficiency occurs in early childhood and reveals hepatomegaly, fasting ketosis, hypoglycemia, and growth restriction. At the same time, muscle phosphorylase kinase deficiency is a rare condition that is associated with myalgia, muscle cramps, and progressive muscle weakness.

Who Gets Affected by Phosphorylase Kinase Deficiency?

Phosphorylase kinase deficiency disease affects males and females in equal numbers. The X-linked forms affect males more than females though females have all the symptoms. It affects 1 in 100000 individuals. Due to some individuals going undiagnosed or misdiagnosed, the exact frequency of the disease in the general population is difficult to determine. Phosphorylase kinase deficiency is rare, and its prevalence is unknown.

What Causes Phosphorylase Kinase Deficiency?

Genes provide and guide instructions for creating proteins that play a key role in bodily functions. When a mutation is present in the gene, the resulting protein product may be inefficient, faulty, or absent. Depending on the protein function, it may affect many organs of the system of body. These mutations can be inherited either in an autosomal recessive manner or an X-linked manner. Glycogen storage disease is caused by mutations in the PHKA1, PHKA2, PHKB, or PHKG2 genes.

What Are the Signs and Symptoms of Autosomal Liver and Muscle Phosphorylase Kinase Deficiency?

The signs and symptoms of deficiency of enzyme phosphorylase kinase present with specific symptoms, and severity and prognosis depend upon the areas of the body that are affected. The symptoms are:

• Enlarged liver (hepatomegaly).

• Hyperkeratosis (high level of ketones in the body).

• Diminished muscle tone.

• Muscle weakness.

• Delayed puberty.

• Low glucose levels.

• High levels of blood ketones during fasting.

• Delay in growth.

• Kids get affected by delayed motor development.

• Hypoglycemia can develop after fasting overnight.

• Shakiness.

• Irritability.

• Unexplained fatigue.

• Headache.

• Pale skin.

• Rapid heartbeat.

Some people have few or no issues with hypoglycemia, while others have severe and recurrent hypoglycemia. Some reports have been recorded, which may result in scar formation in the liver (fibrosis) and also lead to irreversible scar formation of the liver (cirrhosis).

How Is the Diagnosis Made for Phosphorylase Kinase Deficiency?

Diagnosis of phosphorylase kinase deficiency is based upon the identification of its symptoms, a detailed medical history, and clinical evaluation, and many specialized tests like routine laboratory tests such as:

• Elevated Liver Transaminase: Usually, high levels of enzymes are called transaminases.

• Elevations of Cholesterol and Triglyceride Levels: Often, increases in high triglyceride levels can lead to heart disease and stroke.

• Enzyme Essays Tests: Tests are done to identify the presence of the specific enzyme in the organism or tissue.

• Genetic Tests: Tests that identify changes in genes, proteins, and chromosomes.

• Elevated Creatine Kinase Levels: Creatinine levels are seen to increase in many muscle disorders.

• Molecular Genetic Testing: Can detect mutation of specific genes like GSD-IX. Prenatal diagnosis in risk pregnancies can detect prior identification of affected individuals, and evaluation of family members at risk can be done through carrier testing.

What Is the Treatment Provided for Phosphorylase Kinase Deficiency?

The treatment of glycogen storage disease is directed towards certain symptoms that are different in each individual. Comprehensive care is required for this condition. Genetic counseling may result in great benefits.

• Ingestion of sugars is limited, and there are no dietary restrictions.

• A high-protein diet with complex carbohydrates is recommended.

• Prolonged fasting should be avoided, and frequent short meals can be supplemented with uncooked starch and prescribed to avoid hypoglycemia.

• Polycose is used to treat individuals with hypoglycemia or ketosis.

• Individuals who cannot tolerate oral therapy polyose are recommended nutrient supply through the IV line.

• Physical therapy is recommended in cases of muscles affected.

• It is recommended to avoid vigorous exercise and drugs that damage the muscles.

• Allopurinol (Zyloprim), a xanthine oxidase inhibitor, can reduce the uric acid level in the blood and prevents gout and kidney stones in adult life.

• No effective treatment is available for this deficiency, but creatine supplements can be beneficial.

• Blood glucose and ketone levels are monitored periodically.

• Follow-up of periodic checking of liver enzymes and liver involvement is done.

• Regular examination of abdominal ultrasound and magnetic imaging ultrasound (MRI) every 6 to 12 months is done.

Conclusion:

Autosomal liver and muscle phosphorylase kinase deficiency's earliest symptoms begin shortly after birth. Mainly causes hypoglycemia and hepatomegaly. The prognosis is generally considered good with X-linked and certain autosomal forms of the disease. In severe cases, fibrosis and cirrhosis are reported along with X-linked forms. Another severe complication associated with this deficiency is malignant hyperthermia. Individuals who require general anesthesia are more prone to this complication. Malignant hypothermia is a rare, abnormal, potentially life-threatening response to anesthesia drugs and muscle relaxants.