Neonatal Adrenoleukodystrophy (NALD)
What is NALD?
Neonatal adrenoleukodystrophy (NALD) belongs on the Zellweger spectrum, which includes conditions like Zellweger syndrome and Refsum disease. NALD is the moderate form, falling in between Refsum and Zellweger. These three conditions used to be classified independently of each other, but it is now understood that they all fall onto the same spectrum.
Most organs of the body are affected, often resulting in life-threatening complications in early childhood or infancy. Determining the incidence rate is difficult, as this condition is often misdiagnosed, but it is estimated that one of every 50,000 births in the U.S. is affected by one of these three variants.
What are the symptoms of NALD?
Symptoms vary widely between affected individuals. Not everybody will have all of the symptoms listed below, and they can all vary in severity. For those with NALD, the onset typically occurs during infancy. Symptoms include:
- Lack of muscle tone
- Lethargy, poor reaction to stimuli
- Inability to suck or swallow, leading to issues with feeding, weight gain, and growth
- Poor reflexes
- Intellectual disabilities
- Missing developmental milestones
- Involuntary movement of the eyes
- Vision and hearing loss
- Enlarged spleen
- Liver problems
- Heart defects
- Respiratory issues
Those affected also experience facial and skeletal abnormalities. These include high forehead, a flattened face, broad nose bridges with a small and upturned nose, soft spots on the skull, a small jaw, a small chin, an arched palate, malformation of the ears, extra folds of skin on the neck, shallow eye sockets with widely spaced eyes, clubfoot, bent fingers, and hardened spots of calcium on the knee caps and long bones of the limbs.
What causes NALD?
One of 13 genes must be mutated in order to have this condition, all of which are inherited in an autosomal recessive pattern. These genes are involved in peroxisomes, which are structures within the cytoplasm of a cell that are necessary for body function.
The PEX1 gene is most commonly the cause for NALD, with the other 12 being PEX2, PEX3, PEX5, PEX6, PEX10, PEX11, PEX12, PEX13, PEX14, PEX16, PEX19, and PEX26.
How is NALD diagnosed?
Doctors typically notice the characteristic symptoms quickly, which is followed by a clinical evaluation and understanding the patient’s medical history. Blood and urine tests are also used, with genetic testing to confirm a diagnosis.
What are the treatments for NALD?
The first treatment for Zellweger spectrum disorders, Cholbam, was approved in 2015. Early intervention provides the best outcomes. Other treatment includes feeding tubes, anti-epileptic drugs, hearing aids or cochlear implants, vitamin supplements, surgery for cataracts, glasses, adrenal replacement, morning cortisol, adrenocorticotropic hormone, and monitoring for bone diseases.