The Higbee family never planned to become rare disease advocates. But when their daughter Harlow began experiencing health issues, they knew that they would do whatever they could to help. At first, reports First Coast News, doctors grew concerned when Harlow showed signs of hypotonia (low muscle tone) at birth. Six months later, an MRI found that one side of Harlow’s brain was bigger. Eventually, through genetic testing, Harlow was diagnosed with an ultra-rare disease called Pyruvate Dehydrogenase Complex Deficiency (PDCD).
Harlow’s parents, Kim and Rick, found themselves frustrated by the lack of research, with hardly any new research insights over the last 15 years. Even more frustrating was the difficulty the family faced while trying to fundraise. They were often told that the disease had far too small of a population size to raise funds for.
So they jumped into action as advocates. First, they brought Harlow to Dr. Pamela Trapane at UF Health Jacksonville for care; Dr. Trapane placed Harlow on a ketogenic diet. Next, they began starting conversions and advocating for PDCD inclusion on newborn screening panels. Perhaps most importantly of all, they—alongside other families whose children have PDCD—began advocating for increased research.
Right now, the University of Texas Southwestern is running a gene therapy study in murine models of PDCD. The Higbees hope that, in the future, this research will ultimately lead towards a cure. If you’d like to become an advocate or donate to the cause, you may do so at Hope for PDCD.
An Overview of Pyruvate Dehydrogenase Complex Deficiency (PDCD)
Pyruvate dehydrogenase complex deficiency (PDCD) is a rare carbohydrate metabolism disorder. People with PDCD are deficient in one of the three enzymes within the pyruvate dehydrogenase complex. This means that the body cannot properly break down nutrients for energy. PDCD also causes the buildup of lactic acid in the body. The Genetic and Rare Diseases Information Center (GARD) explains that:
The most common form of PDCD is caused by genetic changes in the PDHA1 gene [that] are inherited in an X-linked manner. Pathogenic variants in other genes including PDHB, DLAT, PDHX, DLD, and PDP1 can also cause PDCD…in an autosomal recessive manner.
Symptoms typically begin in infancy, though they may appear at birth or in childhood. These symptoms may become more pronounced after eating high-carbohydrate meals, when sick, or when stressed. Symptoms may include:
- Rapid breathing
- Developmental delays
- Poor feeding
- Ataxia
- Extreme fatigue and lethargy
- Low muscle tone
- Abnormal eye movements
- Brain structural abnormalities
- Seizures
There is no cure for PDCD and no PDCD-specific treatment. Some children benefit from thiamine treatment, antiepileptic drugs, and a ketogenic diet. Dichloroacetate may also be used to treat lactic acidosis.
