Holocarboxylase synthetase is an important mitochondrial enzyme for processing dietary biotin. An hereditary defect in the enzyme impacts gluconeogenesis, amino acid catabolism and fatty acid synthesis.


Inheritance: autosomal recessive (may have affected siblings)


Onset: early onset, from birth to 21 months of age, with most presenting before 3 months of age


Common metabolic findings (present in all or most patients):

(1) metabolic acidosis (ketolactic acidosis)

(2) organic aciduria

(3) hyperammonemia


Respiratory findings:

(1) tachypnea

(2) hyperventilation


Neurologic findings:

(1) lethargy

(2) irritability

(3) abnormal muscle tone (hyper or hypotonia)

(4) seizures

(5) abnormal reflexes (hyper or hyporeflexia)

(6) developmental delay

(7) ataxia

(8) tremor

(9) coma


Skin changes:

(1) skin rash

(2) alopecia


Other findings:

(1) odor of urine

(2) thrombocytopenia

(3) feeding problems

(4) vomiting

(5) hypothermia


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