Abstract
Abstract Glycogen storage disease type IXa (GSD IXa) presents in childhood with hepatomegaly, poor growth, and ketotic hypoglycemia. Clinical course is usually mild, often not requiring treatment with attenuation of symptoms with increasing age. The phenotypic spectrum has recently expanded to include more severe involvement with hepatic fibrosis or cirrhosis warranting dietary therapy. We report a 2-year-old boy with a severe phenotype of GSD IXa presenting with a massive hepatomegaly, significant transaminitis, recurrent ketotic hypoglycemia, and short stature. Aggressive dietary management with regular feeds, frequent uncooked cornstarch doses, and protein supplementation resulted in clinical improvements including enhanced growth velocity, energy levels, overall well-being, and reduction in hepatomegaly with restitutions in biochemical parameters. We concur with a recent report which proposed that GSD IXa is not always a mild condition but instead part of an expanding phenotypic spectrum warranting intensive dietary management to optimize metabolic control and quality of life.
Highlights
Glycogen storage disease type IXa (GSD IXa), known as X-linked liver glycogenosis (XLG), is one of the most common forms of GSD, accounting for approximately 75% of liver phosphorylase-b kinase (PhK) deficiency
Mutations in phosphorylase kinase beta subunit (PHKB) result in PhK deficiency both in liver and muscle; the symptoms from muscle involvement can be mild or absent, making it clinically indistinguishable from the liver PhK deficiencies caused by mutations in phosphorylase kinase liver alpha-subunit 2 (PHKA2) and PHKG2.2 Patients with mutations in g-subunits (PHKG2) are at risk of a more severe phenotype that can present with cirrhosis in childhood.[4,7,8]
We present a 2-year 6-month-old boy with novel a-subunit (PHKA2) gene mutation presenting with severe GSD IXa phenotype in the form of massive hepatomegaly with fibrosis at the time of diagnosis, in addition to growth retardation, recurrent hypoglycemia, ketosis, and significant transaminitis
Summary
Glycogen storage disease type IXa (GSD IXa), known as X-linked liver glycogenosis (XLG), is one of the most common forms of GSD, accounting for approximately 75% of liver phosphorylase-b kinase (PhK) deficiency. PHKA2-related PhK deficiency, known as XLG, is the most common cause of liver PhK deficiency, accounting for about 75% of all GSD IX.[2] Patients with XLG can be divided into 2 biochemical subtypes depending on the enzyme activity in various tissues: XLG type 1 (XLG1 or GSD-IXa1), with reduced activities of PhK in blood cells and liver, and XLG type 2 (XLG2 or GSD-IXa2), with normal PhK activity in blood cells and variable activity in liver.[5] X-linked liver glycogenosis is characterized by hypoglycemia, hepatomegaly, chronic liver disease, growth retardation and delayed motor development, hypercholesterolemia, hypertriglyceridemia, and hyperketosis following fasting These symptoms ameliorate during puberty.[6] Mutations in PHKB result in PhK deficiency both in liver and muscle; the symptoms from muscle involvement can be mild or absent, making it clinically indistinguishable from the liver PhK deficiencies caused by mutations in PHKA2 and PHKG2.2 Patients with mutations in g-subunits (PHKG2) are at risk of a more severe phenotype that can present with cirrhosis in childhood.[4,7,8]. Alanine transaminase (U/L) Aspartate transaminase (U/L) Alkaline phosphatase (U/L) g-glutamyl transferase (U/L) Glucose (mmol/L) Cholesterol (mmol/L) Triglyceride (mmol/L) Lactate (mmol/L) Uric acid (mmol/L)
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