Hepatic glycogen phosphorylase kinase deficiency, a challenging diagnosis

Coralie De Bruyne, Joseph Dewulf, Mina Komuta, Etienne Sokal Published in the journal : May 2015 Category : Pediatrics

Glycogen storage diseases (GSD) are inherited metabolic diseases characterized by glycogen accumulation in the liver and/or muscles. Among liver GSDs, glycogen phosphorylase-phosphorylase kinase deficiency is responsible for GSD Type IX or VI. GSD Type IX results from a glycogen phosphorylase kinase deficiency and is primarily caused by a damage to one of the four different genes coding for the enzyme subunits. The most commonly affected gene is PHKA2, located on X chromosome. These GSDs are usually suspected in the event of hepatomegaly, elevated liver transaminases, and increased postprandial lactate levels, with a trend towards hypoglycemia, though fasting is often well tolerated. The diagnosis is generally made based on enzyme activity measurement in red blood cells and confirmed by genetic analysis. In boys, however, some variants are not characterized by a decreased erythrocyte activity. As a result, and if clinical manifestations are suggestive, the genes involved in GSD IX and VI must be analyzed in order to exclude this diagnosis, with the PHKA2 gene being analyzed first, followed by the PYGL gene (GSD VI).

This report presents our assumptions and diagnostic reflections regarding a clinical case with hepatomegaly, as well as elevated transaminases and postprandial lactate levels. The genetic study allowed us to detect a mutation in the PHKA2 gene that is responsible for the X-linked GSD Type IX, though this condition had previously been excluded.

What is already known about the topic?

The diagnosis of glycogen storage disease Type IX can generally be made based on enzyme activity measurement in red blood cells.

What does this article bring up for us?

• Normal erythrocyte phosphorylase kinase activity does not exclude the diagnosis of GSD Type IX.

• Among boys, some variants are not associated with decreased erythrocyte enzyme activity. Thus, if clinical manifestations are suggestive, the genes involved in glycogen storage diseases IX and VI should be analyzed in order to exclude this diagnosis.

• In this article, we have also reviewed the differential diagnosis of liver glycogen storage diseases

Practical recommendations

• Think of a glycogen storage disease type IX when a patient presents a hepatomegaly, elevated liver transaminases and postprandial high lactate. A tendency to hypoglycemia may be observed through a glycemic profile, but fasting is generally well tolerated.

• Even if the phosphorylase kinase activity is normal in erythrocytes, it is useful to conduct a genetic analysis of PHKA2 and PYGL genes, among boys, to formally exclude a type IX glycogen storage disease.

Key Words

Glycogen storage diseases, phosphorylase kinase, PHKA2, hepatomegaly, hypoglycemia, lactic acid, ketones

Read more

Diagnosis of primary bilateral macronodular adrenal hyperplasia and evaluation of aberrant receptors. A case report.

Corinne Jonas, Christophe Hommel, Julian Donckier Published in the journal : May 2015 Category : Endocrinology

Primary bilateral macronodular adrenal hyperplasia is a rare condition that may be responsible for Cushing's syndrome. We report herein the case of a patient presenting with bilateral adrenal incidentalomas causing subclinical hypercorticism. Aberrant receptors were searched for, suggesting the presence of vasopressin and serotonin receptors. As there is currently no specific treatment available to block these receptors, it has been proposed to follow-up the patient who did not present any hypercorticism-related complication.

Read more

Sclerotherapy of telangiectasias and deep venous thrombosis revealing a genetic clotting disorder

Cécile Courtin, Bernard Bouffioux, Françoise Dobbelaere, Marie-Noëlle Vogeleer, Anaïs Saint-Rémy, Aurélie Coutellier, Jacques Mairesse Published in the journal : September 2015 Category : Dermatologie et Hématologie

Deep venous thromboses following sclerotherapy are very rare, yet occur more frequently in thrombophilic patients. We have here described two cases in which post-sclerotherapy deep venous thrombosis revealed a mutation in the prothrombin gene (Factor II). We have further explained the principles of sclerotherapy with lauromacrogol (polidocanol). We have finally summarized the causes of thrombophilia and provided practical recommendations regarding sclerotherapy in thrombophilic patients.

Read more

Prophylaxis after non-professional exposure to human immunodeficiency virus (HIV): state of the art

Jean-Cyr Yombi Published in the journal : September 2015 Category : Internal Medicine

Infection with the human immunodeficiency virus (HIV) remains a public health concern worldwide. Young adults are the most commonly affected by the pandemic, 40% of new cases involving persons aged between 15 to 24 years. This age group is the most -sexually active. There are four opportunities for HIV prevention. Post-exposure prophylaxis (PEP) by administering anti-retroviral treatment is a prevention tool in a post-coital setting for exposed patients. The probability of HIV transmission depends on the type of exposure, infectivity level of the source, and susceptibility of the person exposed. The risk for a person to acquire HIV following an exposure incident can be calculated by multiplying the risk that the source person is HIV positive by the risk associated with a particular exposure. Prophylaxis is recommended when the risk of transmission is greater than 1/1000, and prophylaxis should be considered when the risk is between 1/1000 and 1/10 000. When this risk is less than 1/10 000, prophylaxis is not recommended. The most recent guidelines recommend administering two nucleoside reverse transcriptase inhibitors (NRTI) associated with either an integrase inhibitor (INI) or a boosted protease inhibitor (PI / r). The treatment should be initiated as soon as possible after exposure, preferably within 24 h, but can be considered up to 72 h. The duration the treatment is 28 days; HIV status should be performed on Day 0 and at 8 weeks with a 4th generation blood test. Lastly, during follow-up, counseling on HIV prevention should be provided.

Read more

Why not dance our way to health?

Olivier S. Descamps, Caroline Daumerie, Sylvie Bourgeois, Sarah Fuller, José Lozano Published in the journal : September 2016 Category : Internal Medicine

Dance is an enjoyable and simple activity, which can be practiced in solo, duo, or group. Numerous studies have already suggested the benefits of dancing for cardiovascular, neurological, and mental health....

Read more

Liraglutide 3 mg ( SAXENDA® ): a new drug for obesity

J.P. Thissen Published in the journal : September 2015 Category : Endocrinologie et Nutrition

Liraglutide, an analog of glucagon-like peptide (GLP)-1, prescribed to date in Type 2 diabetes mellitus at 0.6-1.8mg /day (Victoza®) is now available for the treatment of excess weight at a dose of 3mg/day (Saxenda®). Besides the insulinostimulating properties responsible for its anti-hyperglycemic activity, the drug exerts an anorectic action at the hypothalamus level, thereby promoting weight loss. Liraglutide 3mg is indicated for the treatment of obesity (BMI> 30Kg/m2) or overweight (BMI>27Kkg/m2) in patients with at least one comorbid condition. The agent's exact place in the treatment of obesity, particularly in the long-term, remains to be further specified.

Read more

“Translating clinical trials into daily practice” by an international expert, Professor Giancarlo Agnelli

C. Lambert Published in the journal : September 2015 Category : Hematology/Oncology

Due to the development and approval of new oral anticoagulants (NOACs), the treatment of venous thromboembolic disease (VTE) has changed dramatically over the last years. Our therapeutic habits are evolving, thus raising new issues, especially regarding the use of NOACs in daily practice. The first part of this paper reviews major clinical trials that have led to the approval of NOACs for VTE treatment. In the second part, the international expert Giancarlo Agnelli shares his experiences and recommendations regarding the use of NOACs in VTE.

Read more

Hydrocephalus in children under the age of five: from diagnosis stage to short/middle/long term evolution: a retrospective review of 142 children

Océane Perdaens, Guus Koerts, Marie-Cécile Nassogne Published in the journal : June 2016 Category : Mémoires de Recherche Clinique

Hydrocephalus, a common condition in the pediatric population due to its various etiologies, proves to be an issue in many cases, due to its various etiologies, thereby threatening the children's life-expectancy and neurodevelopmental outcome...

Read more

Retrospective epidemiological study on the management of induced pain in the emergency department

Adrien Maseri, Charles Grégoire, Franck Verschuren Published in the journal : June 2016 Category : Mémoires de Recherche Clinique

Induced pain is defined as short-lasting pain caused by the practitioner in predictable circumstances, potentially prevented by appropriate analgesia or sedation...

Read more

Total proctocolectomy with ileal pouch-anal anastomosis in the management of familial adenomatous polyposis and ulcerative colitis : relevance of endoanal mucosectomy and long-term functional outcomes

Raphaël Lattenist, Daniel Léonard, Radu Bachmann, Christophe Remue, Nora Abbes Orabi, Anne Jouret-Mourin, Olivier Dewit, Pierre Hoang, Hubert Piessevaux, Eleonora Farinella, Alex Kartheuser Published in the journal : June 2016 Category : Mémoires de Recherche Clinique

Total proctocolectomy followed by ileal pouch-anal anastomosis (IPAA) is currently the gold standard in the treatment of familial adenomatous polyposis (FAP) and ulcerative colitis (UC)...

Read more