[I had a female patient with biotinidase deficiency who presented at 3 years of age with ataxia. Serum lactate was 33 (<20). CSF glucose was 47. Remarkably, CSF lactate was 123 (<20). On repeat assay, the lactate was 75.6. Her one year old asymptomatic brother was also found to have biotinidase deficiciency.]
Krishnakumar D, Maw A, Brown R, Hogg S, Calvin J, Parker AP. Abnormal cerebrospinal fluid biochemistry in biotinidase deficiency causing diagnostic conundrum. J Child Neurol. 2014 Jan;29(1):93-5.
Biotinidase deficiency is a treatable cause of infantile epilepsy and the presentation can be nonspecific. The seizures are difficult to differentiate from other causes of epileptic encephalopathy, which generally have a poor prognosis. We report 2 infants who presented with seizures, and whose low cerebrospinal fluid glucose and high cerebrospinal lactate caused a diagnostic dilemma. Subsequent urine organic acids pointed to the correct diagnosis and avoided invasive investigation. The children had a good clinical outcome with resolution of their seizures on biotin treatment.
From the manuscript
[Case 1] Subsequent urine organic acid analysis revealed mild lactic aciduria, moderate increase in 3-hydroxyisovalerate, mild increase in methylcitrate, and a trace of triglylglycine, consistent with biotinidase deficiency. Biotinidase activity was recorded as 0.5 nmol/mL/min, confirming the diagnosis. The child was initially started on phenobarbital and treated with biotin when the diagnosis was confirmed…
[Case 2] Urine organic acids were suggestive of biotinidase deficiency with moderate lactic aciduria, marked increase in 3-hydroxyisovalerate with a slight increase in 3-meth ylcrotonylglycine and methylcitrate. Blood spot acylcarnitines were also abnormal with increased hydroxyisovalerylcarnitine. Biotinidase activity was low at 0.4 nmol/mL/min. Treatment with phenobarbital was instituted at presentation, followed by biotin. She responded well to the biotin and the phenobarbital was subsequently withdrawn. She remains seizure free 2 years after treatment.
Cerebrospinal fluid lactate, blood lactate, and blood glucose results are often available before the urine metabolic screen, as was the case in these children. In both, high cerebrospinal fluid lactate was suggestive of mitochondrial disease, although hypoglycorrhachia would be unusual. Both children had cerebrospinal glucose: plasma glucose ratios consistent with GLUT1 deficiency (ie, <0.40), although raised cerebrospinal fluid lactate is not a feature of GLUT1 deficiency.
The biochemical results caused diagnostic confusion with potential delay of definitive therapy. A muscle biopsy for the investigation of a mitochondrial disorder was being