Hyperinsulinism-hyperammonemia syndrome

Hyperinsulinism-hyperammonemia syndrome (HI/HA syndrome) is a rare genetic disorder characterized by the combination of hyperinsulinism and elevated levels of ammonia in the blood. This condition is typically diagnosed in infancy or early childhood and can lead to severe hypoglycemia and neurological complications if not properly managed.

Etiology

HI/HA syndrome is caused by mutations in the GLUD1 gene, which encodes the enzyme glutamate dehydrogenase. This enzyme plays a crucial role in the regulation of insulin secretion and ammonia metabolism. Mutations in the GLUD1 gene lead to an overactive enzyme, resulting in excessive insulin release and elevated ammonia levels.

Clinical Features

The primary clinical features of HI/HA syndrome include:

• Persistent hypoglycemia due to excessive insulin secretion
• Elevated blood ammonia levels (hyperammonemia)
• Seizures
• Developmental delay
• Poor feeding and growth

Diagnosis

Diagnosis of HI/HA syndrome involves a combination of clinical evaluation, laboratory tests, and genetic testing. Key diagnostic criteria include:

• Persistent hypoglycemia with inappropriately high insulin levels
• Elevated plasma ammonia levels
• Identification of mutations in the GLUD1 gene through genetic testing

Management

Management of HI/HA syndrome focuses on controlling hypoglycemia and hyperammonemia. Treatment strategies include:

• Frequent feeding or continuous enteral feeding to prevent hypoglycemia
• Administration of medications such as diazoxide to reduce insulin secretion
• Use of ammonia scavengers to lower blood ammonia levels
• Dietary modifications to manage protein intake

Prognosis

The prognosis for individuals with HI/HA syndrome varies depending on the severity of the condition and the effectiveness of treatment. Early diagnosis and appropriate management are crucial for preventing severe hypoglycemia and minimizing neurological complications.

Related Pages

• Hyperinsulinism
• Hyperammonemia
• GLUD1
• Hypoglycemia
• Genetic disorder