Inborn error of metabolism present in the neonatal
period and characterized by tachypnea or Kussmaul breathing, hypotonia, and
seizures. Severe metabolic acidosis with ketosis and hyperammonemia. If
present during infancy and childhood, lethargy, hypotonia, seizures ataxia;
apnea/hyperventilation, and frequent stridor are characteristic. Usually
corrected with oral biotin.
Biotinidase Deficiency; Holocarboxylase Synthetase
First described in 1971 by Wolf et al. It was immediately observed that biotin
administration was curative.
1:112,000-129,000 live births (biotinidase deficiency).
Autosomal recessive; more than 40 different
mutations have been described. Gene locus on chromosome 3p25 (biotinidase)
or 21q22.1 (holocarboxylase).
Biotinidase is essential for generation of free
biotin from endogenous recycling or protein-bound biotin found in diet.
Holocarboxylase synthetase is required to catalyze binding of biotin to
carboxylases. Biotin is required as a cofactor for carboxylases within the
body, which are involved in the metabolic pathways for a number of amino
acids, gluconeogenesis, and fatty acid synthesis. Defects in either enzyme
lead to organic acidosis.
Clinical features, particularly skin rash and alopecia,
but variability of symptoms according to importance of deficiency and amount
of free biotin intake. Organic aciduria. Deficiency of specific enzyme
measured in plasma. Included in neonatal screening programs in many
Deficiency of holocarboxylase synthetase presents in more than 50% of cases in the
neonatal period with tachypnea or Kussmaul breathing, hypotonia, and
seizures. Severe metabolic acidosis with ketosis and hyperammonemia.
Untreated patients and those with less severe defects present with mental
retardation, hair loss, and skin lesions (erythematous rash often with
superinfection with Candida). Deficiency of biotinidase presents later in infancy or childhood. Lethargy,
hypotonia, seizures, ataxia; respiratory problems (apnea/hyperventilation,
frequent stridor). Skin manifestations such as periorificial eczematoid
dermatitis and alopecia are less common. Intermittent organic aciduria.
Immune deficiency leads to recurrent infections. If untreated, psychomotor
delay and permanent neurologic deficit (hearing loss, optic atrophy).
Treatment: In both conditions there is a dramatic response to biotin, with resolution
of clinical and biochemical abnormalities but not fixed neurologic sequelae.
The dose of biotin varies from 2.5 to 5 mg/week (partial deficiency in
biotinidase) to 2.5 to 10 mg/day (profound deficiency in biotinidase) or
even more; 10 to 20 mg/day in case of holocarboxylase deficiency.
Patient should be receiving his or
her usual biotin supplements until the morning of surgery. However, if the patient has not received
biotin supplementation, a complete evaluation of the cardiovascular,
respiratory, and muscle functions should be done. Seizure medications should
be continued until the morning of surgery.
Anesthesia management in this condition
has not been described. Patients who are receiving adequate supplementation
with biotin may be free of clinical and biochemical abnormalities.
Intravenous administration of biotin may be necessary in the perioperative
period. Perioperative monitoring of glycemia, lactates, and ammonium (NH4). If the
patient has not received his or her medication, then cardiovascular,
respiratory, and muscular ...