Pyruvate Dehydrogenase Deficiency (PDCD)

Summary by

Adil Parvaiz
231451928
BIOT – 302 – A
Submitted to

Dr. Wajahat Hussain

Summary
 The article under study, written by Dr. Richard E Frye, MD, PhD, who is an expert in
human neurology and specializes in child diseases. The focus of given article is the inspection of
Pyruvate Dehydrogenase Complex Deficiency (PDCD), its causes, importance, investigative
techniques, medications, and occurrence. PDCD is categorized under common
neurodegenerative disorders linked with imbalance of mitochondrial metabolism. The deficiency
of PDC disturbs the citric acid cycle, resulting in deprivation of energy in body. The disease is
most common in infants and has rare chance to occur in adults.
The importance of Pyruvate dehydrogenase Complex is briefed as it turns pyruvate into
acetyl-coenzyme A (ACoA), that is a key substrate to produce citrate. The production of citrate
is reduced to deficiency of PDC which results in halt of the citric acid cycle and an energy deficit
emerges in the body. This lack of energy leads to congenital brain malformation and other
neurological diseases. The cases of PDCD occur rarely i.e., 1:50,000. For X-linked cases, there is
mostly a chance of 2 in 3 risk that mother would be unexpressing carrier. For recessive case,
which is rare, there is a 1 in 4 repetition risk. In-frame mutations of the X-linked E1 alpha gene
has is held responsible in mild cases.
Moving on, to the mortality, if the disease onsets at neonatal or infantile stage, there is rare
chance of survival for the child. However, if disease occurs in later childhood disease, the patient
may or may not survive into adulthood. The survival chance for infants with PDC activity lesser
than 15% is almost zero, whereas, if PDC activity is above 25% it is regarded as less severe and
is termed as Ataxia or mild psychomotor delay, the morbidity of which can be delayed by some
therapies. PDCD mostly affects males, rather than females because the disease is X-linked. Most
female carriers may have mild symptoms but are much lower than the X-linked form of disease.
Ethnicity on the other hand, is seen having no effect on the occurrence of disease and age ranges
from prenatal to early childhood, depending upon the residual activity of PDC. There are three
basic substrate processing enzymes that compose the intramitochondrial PDC and a dysfunction
in all components can lead to PDCD. However, the most usual form of PDCD is resulted due to
mutations in the X-linked, E1 alpha gene and all other causes are due to modifications in
recessive genes.
The article transcends further explaining different laboratory procedures indicate and
identify the PDCD in patients. Such as, high lactate and pyruvate levels in blood and
cerebrospinal fluid indicate error in mitochondrial metabolism, and serum and urine amino acid
analysis indicate hyperalaninemia. Consultation with an expert is important for proper diagnosis
and treatment. Genetic counseling can prevent any future cases of PDCD for parents. The disease
can trigger renal failure and a nephrologist should be consulted and the disease can also cause
complications in anesthesia for which anesthesiologist should be consulted before any procedure
that requires anesthesia. The diet of patients affected by PDCD should have limited carbohydrate
content and Fat intake should be 65 – 80 % of caloric intake. Ketogenic diet must be opted for
appropriate lactic acid level. At last, the medication of PDCD include supplements of cofactors,
with thiamine, carnitine, and lipoic acid. Dichloroacetate sodium is the drug that acts as an
enzyme activator for PDC which inactivates kinase and promotes pyruvate oxidation by
inhibiting the lactate production.
 In conclusion, the entire article can be winded up as, Pyruvate Dehydrogenase Complex
deficiency is a common neurological disease which is X-linked mostly occurring in male infants
and rarely promoting to adulthood. The lifespan of patient depends upon the enzyme residue
level. The disease halts the citric acid cycle, depriving body of energy. Different lab tests
contribute to diagnosis of PDCD, and proper consultation must be opted by the parents for
treatment, prevention, and diagnosis. Ketogenic diet is preferrable for the patients and
medications include cofactor supplements along with drug that promotes pyruvate oxidation.