Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.
If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.
This week’s study is…
Elevated Oxysterol and N-Palmitoyl-O-Phosphocholineserine Levels in Congenital Disorders of Glycosylation
We previously published about this research in a story titled “A Biomarker for Niemann-Pick Disease Type C Could Improve Congenital Disorders of Glycosylation Diagnosis” which can be found here. The study was originally published in the research journal Journal of Inherited Metabolic Disease. You can read the full text of the study here.
This research team was affiliated with the National Institutes of Health (NIH).
Niemann-Pick disease Type C1 (NPC1) is a rare neurodegenerative disorder affecting the metabolism of cholesterol. One biomarker that is commonly used to test for the disease is N-palmitoyl-O-phosphocholineserine (PPCS). Congenital disorders of glycosylation (CDGs) are a group of diseases that impact the process that cells use add certain sugar molecules to proteins. In the case study of an infant that suffered an early death, the research team appears to have discovered that PPCS could also be used to diagnosed certain types of CDG.
The case study involved a male infant that was three months old. The boy presented with high oxysterol levels and an enlarged liver; oxysterols are molecules that known to derive from cholesterol. Unfortunately, the boy passed away, so the researchers decided to conduct tests for gene abnormalities that can trigger severe liver disease in the first few months of life. However, these evaluations did not lead to an answer; they continued genetic testing and ultimately found an alteration in the gene ATP6AP1. This mutation is known to be responsible for a form of CDG.
The scientists were not expecting this finding since the boy’s symptoms were similar to NPC1. They decided to investigate if other forms of CDG presented similarly. They did this through the evaluation of a number of samples provided by NIH collaborators and other partners that follow CDG patients. What they found was the PPCS was elevated in CDG linked to mutations impacting the following genes: ALG1, ATP6AP1, ALG8, and PMM2.
The team concluded that children with elevated oxysterols and PPCS with liver disease should not only be tested for NPC1, but for CDG as well.
About Niemann-Pick Disease Type C
Niemann-Pick disease type C is a form of lysosomal storage disease which is characterized by a deficiency not in an enzyme, but most typically in a type of transporter protein that prevents water soluble molecules from moving within a cell. It is caused by mutations of either the NPC1 or NPC2 gene. There is broad disparity in the severity and presentation of symptoms in Niemann-Pick disease type C, making symptoms an unreliable method for diagnosis. They may appear in childhood or as late as a patient’s sixth decade of life. Such symptoms include spleen and/or liver enlargement, jaundice, severe depression, ataxia, epilepsy, difficulty speaking and swallowing, dystonia, poor muscle tone, bipolar disorder, microcephaly, progressive loss of hearing, progressive dementia, and psychosis. Most treatment is supportive, but there are some medicines that can delay disease progression and prolong life. Lifespan is connected to the onset of symptoms, with those with the earliest symptoms usually dying sooner. To learn more about Niemann-Pick disease type C, click here.
About Congenital Disorders of Glycosylation
Congenital disorders of glycosylation (CDG) are a group of genetic metabolic disorders which can sometimes cause severe and lethal dysfunction of a variety of body systems and organs, such as the intestines, nervous system, and muscles. These disorders are quite rare and are not well known. While there are a wide variety of different disorders that fall under CDG, they can be classified into type I (which affects lipid-linked oligosaccharides) and type II (which affects protein-bound oligosaccharides). Though signs and symptoms differ between the different variants, they often include vision problems, ataxia, low muscle tone, peripheral neuropathy, failure to thrive, reduced brain volume, certain structural deformities, liver disease, and seizures. There is a dire need for disease-modifying treatments for CDG, as most forms do not have any available treatment. The severity of symptoms can vary widely. To learn more about these disorders, click here.
Why Does it Matter?
Congenital disorders of glycosylation are a several group of metabolic disorders that can result in devastating effects. These problems are only exacerbated by delays in diagnosis, which is a common problem across many different rare diseases.
Through the discovery of a new diagnostic method that could help detect multiple forms of CGD, patients are more likely to get an accurate diagnosis more quickly; while treatment for CGD is very limited in effectiveness, patients will still have a better chance if they get a correct diagnosis in a timely fashion.