Asymptomatic adults and older siblings with biotinidase deficiency ascertained by family studies of index cases

Abstract

We report 32 biotinidase-deficient patients detected by family studies in the index cases. The study group consisted of 10 mothers, 4 fathers and 18 siblings. There were 17 individuals (3 mothers, 4 fathers and 10 siblings) with profound biotinidase deficiency (BD) (< 10% of mean normal activity) and 15 (7 mothers and 8 siblings) with partial BD (10-30% of mean normal activity). In the profound BD group, only three siblings were symptomatic. Dermatitis, microcephaly, developmental delay and convulsions were observed. The patients with partial BD did not have any clinical symptoms except one sibling with borderline IQ score. None of the parents was symptomatic. Family investigation of patients with BD is very important for the detection of asymptomatic patients who are at risk of exhibiting symptoms at any age. Careful evaluation of these untreated individuals with BD is important to obtain additional information about the natural history of this disorder and may provide clues to phenotype-genotype relationships and treatment regimes.

A Case of Biotinidase Deficiency in an Adult with Respiratory Failure in the Intensive Care Unit

“…Two months earlier, she had been admitted to another ICU with tachypnea and hyperventilation. Previous arterial blood gas analysis had revealed respiratory alkalosis with a pH of 7.60, paCO 2 of 12 mmHg, PaO 2 of 103 mmHg, lactate of 2.6 mmol/L, BE of 9.4 mmol/L, HCO 3 -of 12.3 mmol/L and Cl -of 100 mmol/L. While the patient was being monitored in our ICU, we found no systemic disorder.…”

“…The major symptoms of BD are hypotonia, respiratory abnormalities, ataxia, vision and hearing loss, skin lesions, alopecia, developmental delays, metabolic acidosis and hyperammonemia (2). The worldwide incidence of this disease is 1 per 60,000 births (3).…”

Clinical utility gene card for: Biotinidase deficiency—update 2015

“…Asymptomatic Individuals having partial biotinidase deficiency or even sometimes profound biotinidase deficiency may be clinically asymptomatic. 22 In rare cases, due to the absence of any biotin therapy, stress might trigger development of symptoms in these individuals, including principally hypotonia, skin rash, and hair loss; 4,10,20,21 more similar observations would be necessary however to assess the genuine risk for developing biotinidase deficiency associated with stress. Biotin treatment prevents the development of symptoms in affected children identified before they have clinical findings or are identified by newborn screening.…”

Biotinidase deficiency: “if you have to have an inherited metabolic disease, this is the one to have”

“…Several adults with profound biotinidase deficiency identified through family studies have never exhibited symptoms. 44,45 In addition, several enzyme-deficient siblings of symptomatic children have apparently never exhibited symptoms. It is possible that these individuals would become symptomatic if stressed.…”