Glycogenosis type IX

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Classification according to ICD-10
E74.0 Glycogen storage disease (glycogenosis)
ICD-10 online (WHO version 2019)

The glycogen storage disease type IX (English glycogen storage disease type IX , GSD IX), or glycogen storage disease type 9 , as phosphorylase kinase deficiency referred to and belongs to the group of the glycogen storage diseases , and is a rare inherited metabolic disorder . The cause is an enzyme defect in the phosphorylase kinase (PhK), which disrupts the breakdown of glycogen ( glycogenolysis ) in the liver and / or muscles .

Since the phosphorylase kinase is required to activate glycogen phosphorylase , there is a clinical overlap with glycogenosis type VI (Hers disease) . According to earlier nomenclature, phosphorylase kinase deficiency in the liver was referred to as a subtype of Hers disease, or glycogenosis type XIII.

Subtypes

Depending on the affected subunit of the phosphorylase kinase enzyme and the affected tissue (muscle and / or liver), different subtypes of glycogenosis type IX are distinguished.

Subtype PhK subunit tissue gene Inheritance
IXa α liver PHKA2 X-linked
IXb β Liver and muscle PHKB autosomal recessive
IXc γ liver PHKG2 autosomal recessive
IXd α muscle PHKA1 X-linked

Clinic and course

The main symptoms are mild to severe ketotic hypoglycaemia or ketosis with normal blood sugar levels, hepatomegaly , growth retardation, hyperlipidemia and muscle hypotension . Usually symptoms become noticeable in early childhood. A broad spectrum is known with regard to the course. It is often comparatively mild compared to other types of glycogen storage diseases and the symptoms regress with age. However, if untreated, liver complications such as fibrosis , cirrhosis and adenomas can occur, particularly in patients with elevated liver transaminases .

The most common subtype IXa due to the X-linked inheritance is one of the main causes of ketotic hypoglycaemia in boys.

diagnosis

Traditionally, the detection of reduced enzyme activity of the phosphorylase kinase in the liver, muscles or blood is used for diagnosis in conjunction with the clinical findings. For the exact determination of the subtype, to avoid liver and muscle biopsies , and because the in vitro detection of reduced PhK activity is not always successful, the molecular genetic detection of mutations in the affected genes is a good choice for diagnosis. By Next Generation Sequencing (NGS), it is possible to study multiple genes simultaneously.

therapy

Previously, type IX glycogenosis was viewed as a mild disorder that hardly required treatment. In the meantime, however, complications such as cirrhosis of the liver are known which, if left untreated, can occur in all subtypes. Less severely affected patients also benefit from therapy , as this can normalize blood values ​​and liver findings, and growth, strength and endurance as well as the general quality of life are improved.

As with glycogenosis type VI (Hers disease), patients should avoid long periods of fasting and frequent smaller meals, but limit the amount of simple sugars and other rapidly absorbable carbohydrates per meal. Uncooked corn starch plays an important role in nutritional therapy , as it is digested particularly slowly and thus the blood sugar level can be supported for several hours. A very protein-rich diet is indicated, if necessary with protein supplementation , as gluconeogenesis can convert amino acids into glucose . A lack of protein can also be the cause of hypotension in subtypes IXa and IXc, which actually only affect liver enzymes.

The goal of nutritional therapy is to prevent hypoglycaemia and ketosis . High blood sugar levels after meals should also be avoided to minimize further glycogen storage. Regular measurement of the blood sugar level and the ketones in the blood is recommended to check the metabolism .

With strict metabolic control, the prognosis is good. More severe cases of type IXa with the onset of liver cirrhosis have also been described in which the condition of the liver and the general condition improved significantly under structured therapy with uncooked corn starch and proteins.

Web links

Individual evidence

  1. ↑ a b c d e f g Margaret A. Chen, David A. Weinstein: Glycogen storage diseases: Diagnosis, treatment and outcome . In: Translational Science of Rare Diseases . tape 1 , no. 1 , August 26, 2016, ISSN  2214-6490 , p. 45-72 , doi : 10.3233 / trd-160006 .
  2. ↑ Jennifer Goldstein, Stephanie Austin, Priya Kishnani, Deeksha Bali: Phosphorylase Kinase Deficiency . In: GeneReviews . University of Washington, Seattle, Seattle (WA) May 31, 2011, PMID 21634085 ( nih.gov [accessed May 1, 2017]).
  3. ↑ Irene J. Hoogeveen, Rixt M. van der Ende, Francjan J. van Spronsen, Foekje de Boer, M. Rebecca Heiner-Fokkema: Normoglycemic Ketonemia as Biochemical Presentation in Ketotic Glycogen Storage Disease . In: JIMD reports . tape 28 , January 1, 2016, ISSN  2192-8304 , p. 41–47 , doi : 10.1007 / 8904_2015_511 , PMID 26526422 , PMC 5059202 (free full text).
  4. ↑ Laurie M. Brown, Michelle M. Corrado, Rixt M. van der Ende, Terry GJ Derks, Margaret A. Chen: Evaluation of glycogen storage disease as a cause of ketotic hypoglycemia in children . In: Journal of Inherited Metabolic Disease . tape 38 , no. 3 , May 1, 2015, ISSN  0141-8955 , p. 489-493 , doi : 10.1007 / s10545-014-9744-1 .
  5. ↑ J Hendrickx, P Lee, JP Keating et al .: Complete genomic structure and mutational spectrum of PHKA2 in patients with x-linked liver glycogenosis type I and II. In: American Journal of Human Genetics . 1999, p. 1541-1549 , doi : 10.1086 / 302399 .
  6. ↑ Laurie A. Tsilianidis, Laurie M. Fiske, Sara Siegel, Chris Lumpkin, Kate Hoyt: Aggressive Therapy Improves Cirrhosis in Glycogen Storage Disease Type IX . In: Molecular Genetics and Metabolism . tape 109 , no. 2 , June 1, 2013, ISSN  1096-7192 , p. 179-182 , doi : 10.1016 / j.ymgme.2013.03.009 , PMID 23578772 , PMC 3672367 (free full text).