ALDH7A1 gene

Also known as: AASADH Deficiency, ALDH7A1 Deficiency, Alpha Aminoadipic Semialdehyde (α-AASA) Dehydrogenase Deficiency, Antiquitin (ATQ) Deficiency, PDE-ALDH7A1


1. The disease

Pyridoxine-dependent epilepsy – ALDH7A1 (PDE-ALDH7A1) is a rare neurometabolic disease characterized by recurrent intractable seizures in the prenatal, neonatal and postnatal period characterized not well controlled with anti-seizure medications that are responsive clinically and electrographically to large daily supplements of pyridoxine (vitamin B6).

2. The Symptoms

Phenotypic spectrum that ranges from classic to atypical PDE-ALDH7A1. Intellectual disability is common, particularly in classic PDE-ALDH7A1. Lack of early signs or symptoms does not exclude the diagnosis.

  • Classic PDE-ALDH7A1: Untreated seizures begin within the first weeks to months of life. Dramatic presentations of prolonged seizures and recurrent episodes of status epilepticus are typical; recurrent self-limited events including partial seizures, generalized seizures, atonic seizures, myoclonic events, and infantile spasms also occur. Electrographic seizures can occur without clinical correlates.
  • Atypical PDE-ALDH7A1: Findings in untreated individuals can include late-onset seizures beginning between late infancy and age three years, seizures that initially respond to anti-seizure medications and then become intractable, seizures during early life that do not respond to pyridoxine but are subsequently controlled with pyridoxine several months later, and prolonged seizure-free intervals (≤5 months) that occur after discontinuation of pyridoxine.

3. Actions to take in case of early diagnosis

  • Babies with a positive genetic test (having 2 pathogenic variants or 2 copies of a single pathogenic variant in ALDH7A1 gene) should continue breastfeeding.
  • Early treatment is essential in preventing chronic symptoms.
  • Biochemical correlation is essential for confirming diagnosis with increased concentration of α-aminoadipic semialdehyde (α-AASA) in urine and/or plasma.
  • PDE-ALDH7A1 is a lifelong disease that requires lifetime management and regular follow-up with a metabolic physician and dietician, a part from a multidisciplinary approach to care.
  • The International PDE Consortium has published clinical practice guidelines for PDE-ALDH7A1. Effective treatment requires lifelong pharmacologic supplements of pyridoxine; the rarity of the disorder has precluded controlled studies to evaluate the optimal dose. The guidelines recommend the following doses by age: newborns 100 mg/day; infants 30 mg/kg/day with a maximum of 300 mg/day; and children, adolescents, and adults 30 mg/kg/day with a maximum of 500 mg/day. To prevent exacerbation of clinical seizures and/or encephalopathy during an acute illness, the daily dose of pyridoxine may be doubled for several days.
  • Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.

 4. For more information