Profound Biotinidase Deficiency in a Child With Predominantly Spinal Cord Disease

Abstract

Biotinidase deficiency is an autosomal recessively inherited disorder that manifests during childhood with various cutaneous and neurological symptoms particularly seizures, hypotonia, and developmental delay. Spinal cord disease has been reported rarely. We describe a 3-year-old boy with profound biotinidase deficiency who presented with progressive spastic paraparesis and ascending weakness in the absence of the usual characteristic neurological manifestations. Supplementation with biotin resulted in resolution of paraparesis with persistent mild spasticity in the lower limbs. DNA mutation analysis revealed that he was homozygous for a novel missense mutation (C>T1339;H447Y) in the BTD gene. This case indicates that biotinidase deficiency should be included in the differential diagnosis of subacute myelopathy and emphasizes the importance of a prompt diagnosis to prevent irreversible neurological damage.

Biotinidase deficiency should be considered in individuals exhibiting myelopathy with or without and vision loss

“…Spinal cord imaging usually shows hypodensity, demyelination and/or edema of the spinal cord that may extend from the brainstem/medulla down the spine involving the cervical, thoracic or entire spinal cord, [10,13,19]. It is important that the location, bulbar, upper and/or lower extremities, or severity of the peripheral symptoms may correlate with the degree of involvement of the cord observed on imaging.…”

“…Of the individuals who have had mutation analysis, all have had missense mutations with some residual enzymatic activity [10,13,19]. Of those who have had mutation analysis, none of those tested have had null mutations resulting in the complete absence of enzyme or enzyme activity.…”

“…Finding oligoclonal bands and elevated immunoglobulin G concentrations in cerebrospinal fluid have been used as markers for certain immunological disorders, such as transverse myelitis, neuromyelitis optica and multiple sclerosis, which are commonly treated with steroids and intravenous immunoglobulins. Other individuals were assumed to have transverse myelitis so they too were treated with steroids and intravenous immunoglobulins [13,15,16,20,22]. None of these individuals improved while on a course of anti-inflammatory medications which often took days to weeks to assess that they were ineffective.…”

Biotinidase Deficiency Accompanying Hair Changes and Periorificial Lesions: A Case Report

“…Kısmi biotin eksikliğinde ise kesin veriler olmamakla beraber 1-10 mg/gün biotin ile hastalığın semptomları baskıla-nabilir (5). Tedavi ile dermatolojik ve nörolojik bulgular hızla gerilerken, duyma ve görme bozuklukları ise tedaviye daha dirençlidir (10). Olgumuzda da saç dökülmesi ve periorifisyal dermatit nedeniyle akrodermatitis enteropatika düşünül-dü.…”

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

“…28 Some untreated children have exhibited spinal cord disease characterized by progressive spastic paresis and myelopathy. 29 Older affected children may develop ataxia and developmental delay. Many symptomatic children with biotinidase deficiency exhibit a variety of central nervous system abnormalities on magnetic resonance imaging or computerized tomography of the brain.…”