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Glycogen Storage Disease Type Ia (GSD Ia)

Name of disease:

Glycogen Storage Disease Type Ia (GSD Ia)

ICD-10 diagnosis code:

E74.01

Causes:

GSD Ia is caused by mutations in the G6PC gene encoding the phosphatase of the microsomal glucose-6-phosphatase system.

Mode of inheritance:

  • Glycogen storage disease (GSD) type Ia is an inherited autosomal recessive metabolic disease which means both copies of the gene in each cell have mutations.
  • The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but they typically do not show signs and symptoms of the condition.

Prevalence:

Less than 1:50,000

Diagnosis:

For the diagnosis of the various forms of glycogen storage disease type I molecular genetic analyses are reliable and convenient alternatives to the enzyme assays in liver biopsy specimens.

Age of onset:

6 months old

Common signs and symptoms:

  • In young infants, initial symptoms due to hypoglycaemia are often non-specific (such as feeding difficulties or apnoea) but may include features associated with epinephrine release (e.g. autonomic system (neurogenic) symptoms such as tremors, paleness and sweating), cerebral glycopenia (e.g. symptoms such as hunger, irritability, seizures, somnolence and coma), lactic acidosis (e.g. respiratory compensation by hyperventilation) and secondary systemic consequences (e.g. cyanosis) improving in the short-term after feedings.
  • Severe (generally hypoketotic) hypoglycaemic episodes relating to increased fasting time or intercurrent illness or disease may occasionally lead to coma and sudden infant death.
  • Older infants may also present with failure to thrive and a protruding abdomen.
  • Other common clinical presentations include doll-like faces, growth failure, delayed development and hypotrophic muscles.
  • Long-term consequences of GSD Ia if left untreated include growth retardation, delayed puberty, gout, arterial and (rarely) pulmonary hypertension, osteoporosis or osteopenia, polycystic ovary syndrome, hepatocellular adenoma (HCA), hepatocellular carcinoma (HCC), chronic renal disease and renal failure, neuropathy, and cognitive delays and epilepsy because of repeated or severe hypoglycaemic events.
  • Nutritional deficiencies (protein and vitamin B12, folic acid, and vitamin D) are often observed in treated individuals because of the dietary restrictions and lack of appetite associated with daily uncooked cornstarch (UCCS) supplementation to prevent hypoglycaemia; therefore, a complete multivitamin is recommended.

Available treatment (medicinal and non-medicinal):

  • Management of individuals with GSD Ia involves a high degree of personalized medicine.
  • The cornerstone is based on medically prescribed dietary treatment and there are no approved pharmacological therapies that address or correct the underlying cause of the disease.
  • Oral glucose replacement therapy in the form of uncooked cornstarch (UCCS) is used in addition to regular meals and snacks to manage blood glucose levels, and adjunct therapies are administered to manage secondary manifestations of the disease.
  • In addition to maintaining euglycaemia (thus preventing hypoglycaemia), the aims of disease management are to avoid acute metabolic derangement, prevent acute and long-term complications, and ensure normal psychomotor development and good quality of life (QoL).
  • Additional therapies may be required to treat hyperuricaemia, hyperfiltration, albuminuria, hyperlipidaemia, hypocitraturia, arterial hypertension and osteoporosis or to prevent long-term complications such as HCA, HCC, and chronic renal disease and renal failure as well as to normalize growth.

Disease management tips:

  • Individuals with GSD Ia must always carry UCCS preparations with them as standard and may require extra for use in emergencies.
  • Timing of UCCS ingestion also needs to be carefully planned around mealtimes as it can lead to reduced appetite and ultimately anorexia, which coupled with the restricted diet can result in nutritional deficiencies.
  • Strict home/self-monitoring of blood glucose levels and adjustment of UCCS dosing is required to ensure appropriate glycaemic control for daily activities.
  • Children with GSD of any type can take part in sports, but contact sports such as rugby or karate should be avoided.
  • A plan of care should be in place before the patient child starts school. Speak to the teachers to ensure that they are able to meet the child’s needs during the school day.

References:

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