Neonatal adrenoleukodystrophy

L’adrénoleucodystrophie néonatale (NALD) est une maladie neurodégénérative rare qui appartient au groupe des maladies peroxysomales héréditaires. Elle touche entre 1/50 000 et 1/100 000 nouveau-nés, affecte aussi bien les garçons que les filles, et débute à la naissance ou dans la petite enfance.

Neonatal adrenoleukodystrophy (or NALD) is a neurodegenerative disease belonging to the group of peroxisomal disorders. It is a variant of the Zellweger syndrome.

Despite its name, this disease is distinct from X-linked adrenoleukodystrophy.

 

 

Description

Neonatal adrenoleukodystrophy begins at birth or in early childhood and affects both girls and boys. Its frequency varies between 1 in 50 000 and 1 per 100 000 births.

It is characterized by seizures at birth, a diffuse encephalopathy, impaired vision and hearing, peripheral neuropathy, facial dimorphism, growth impairment and a severely delayed psychomotor development. The neurological regression is progressive. Moderate to severe hypotonia and liver hypertrophy are also described.

In most cases, a severe adrenal insufficiency occurs: the adrenal glands are severely atrophied and plasma ACTH levels were markedly elevated.

The majority of children die in infancy.

 

From a biochemical point of view, multiple abnormalities are observed: elevated levels of plasma very long chain fatty acids (VLCFA), of phytanic acid and of bile trihydroxycoprostanic acid.
Genetics
Neonatal adrenoleukodystrophy is an autosomal recessive inherited disease. Thus, for a couple whose members are both carriers of the mutation, the risk of having an affected child (girl or boy) is 25% for each pregnancy.
The genes responsible for the disease belong to the family of PEX genes (genes involved in peroxisome formation and protein transport) specifically PEX5 and PEX1. The lack of interaction between PEX1 and PEX6 has also been identified as a cause of the disease.
Diagnosis
It is based on the determination of plasma VLCFA, phytanic acid, bile and pipecolic acids intermediates
Treatments
Treatment of adrenal insufficiency
The extremely simple treatment is based on prescription of hydrocortisone or fludrocortisone. This daily oral treatment is essential and can never be stopped.
Treatment of symptoms
A multidisciplinary care will improve the children quality of life: reduction of pain, stiffness, spasticity, treatment of orthopedic complications, tube-feeding to allow adequate nutrient intake. 
Psychological care
This care should include not only the patient but also brothers and sisters of affected boys, parents, spouse and often several members of the same family.