Let’s start with a little vocabulary lesson. Today’s word? Biomarker. A biological marker, or biomarker, refers to some sort of measurable indicator of disease. For example, blood pressure, cellular gene expression, and blood enzyme levels may all be used as biomarkers in certain research or evaluations. A news release from the National Institute of Child Health and Human Development (NICHD) at the NIH recently discussed how biomarkers for Niemann-pick disease type C1 (NPC type 1 or NPC1) could potentially be used in the diagnostic process for congenital disorders of glycosylation (CDGs). 

Biomarker Evaluation

Congenital disorders of glycosylation include conditions like CDG-1a; these rare inherited conditions cause a problem with glycoprotein production. The body makes deficient or non-functional enzymes that can’t play a role in glycosylation, or adding sugar molecules to proteins. CDGs can affect multiple body systems. Symptoms may vary from hypotonia (poor muscle tone) and developmental delays to organ failure and failure to thrive. 

Within this study, published in the Journal of Inherited Metabolic Disease, the authors share a case study of a young baby boy. At just 3 months old, the baby presented with raised oxysterol levels and liver enlargement, both of which can be used to diagnose NPC type 1. But further testing after the child died showed no NPC1 or NPC2 mutations. Instead, testing showed that the child had an ATP6AP1 mutation relating to a congenital disorder of glycosylation. 

This led researchers to wonder what other overlaps existed. They found that children with NPC type 1 had elevated N-(3β,5α,6β-trihydroxy-cholan-24-oyl) glycine (TCG) and N-palmitoyl-O-phosphocholineserine (PPCS) levels, whereas children with CDGs only had elevated PPCS levels. 

In the future, the authors suggest that doctors test infants with liver disease and high PPCS levels for both NPC1 and CDGs. 

What is Niemann-Pick disease type C (NPC)? 

There are three types (A, B, and C) of Niemann-Pick disease, a rare and fatal inherited metabolic condition. As described briefly above, NPC1 and NPC2 gene mutations cause NPC; SMPD1 mutations play a role in Niemann-Pick type A and B. These gene mutations prevent the body from properly metabolizing cholesterol and lipids (fats), leading to cellular death. NPC is variable in symptoms, presentation, age, and severity. In many cases, a diagnosis is given perinatally or in early infancy. However, some individuals may not present symptoms until adulthood; these individuals may show neurological symptoms that mimic mood disorders such as bipolar disorder. Additional NPC symptoms may include:

• Cholestasis (abnormal bile flow)
• Failure to thrive
• Jaundice (yellowing of the skin, eyes, and mucous membranes)
• Enlarged liver and spleen
• Hypotonia (low/poor muscle tone)
• Fetal ascites (abnormal abdominal fluid accumulation)
• Frequent respiratory infections
• Difficulty speaking and swallowing
• Vertical eye movement paralysis
• Hearing loss
• Dementia 
• Severe liver disease

Experimental treatments have shown promise for NPC. Unfortunately, there are no FDA-approved treatments available yet.