Homocystinuria is More Common Than We Thought, It’s Just Not Detected Well in NBS

Most patients diagnosed with Homocystinuria (HCU), a rare metabolic disorder, don’t receive their diagnosis until later in life. Scientists were at a loss for why patients with phenylketonuria (PKU), a similar disorder, were diagnosed much earlier. It comes down to ineffective newborn screening (NBS). It turns out that although HCU is actually more common than PKU, the HCU diagnostic process is simply lacking.

Both conditions have newborn screening, but a new evaluation has shown that HCU is normally not detected during the screening process while PKU is. This results in the vast majority of HCU diagnoses to occur between the ages of 44-64. PKU is typically diagnosed between birth to age 11.

The main problem of a later diagnosis is, of course, that it takes HCU patients far too long to receive the treatment they need.

The Conditions

HCU and PKU are both caused by the body’s inability to turn food into energy. They are both genetic and both affect metabolism.

Classical Homocystinuria results when the body is deficient in cystathionine beta synthase (CBS), an enzyme which works to convert methionine to homocysteine to cysteine. Elevated levels of homocysteine can cause cardiovascular, skeletal, opthalmic, and neurologic conditions. These symptoms can become debilitating if not treated.

Orphan Technologies is working to develop an enzyme therapy treatment for the complications caused by HCU. But currently, the only treatment given to patients is simply a protein restricted diet. Unfortunately, the amount of protein patients are allowed to consume is so low, compliance is extremely difficult. When the diet is not followed exactly, patients suffer poor metabolic control.

The moral of the story

The moral of the story is, we need to develop not only new therapies to treat HCU, we need to uncover better ways to detect its presence. Being diagnosed 40-60 years earlier than the current diagnostic averages could be life-changing for HCU patients.

Not only does NBS data show this need, a recent study has shown a staggering number of people living with HCU are still undiagnosed. In an analysis of 1.9 million people, 15,012 had high enough levels of homocysteine to be in the range of HCU. However, only 10% of those individuals had received a HCU diagnosis. This indicates that there may be many individuals living with HCU who still do not have a diagnosis.

You can read more about these studies and some of the ongoing research for HCU and PKU here.

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