extremely rare autosomal recessive disorder. The disease has its onset in childhood, and progresses through three distinct stages. Stage I of the disease is characterized by a subacute encephalopathy of undefined origin that includes confusion, vomiting, and a history of febrile illness. By stage II, this progresses into acute encephalopathy with sudden loss of developmental milestones, slurred speech, loss of motor function, and development of quadriparesis or quadriplegia, along with seizures. If left untreated, the disease progresses to stage III, characterized by an akinetic mute state, which culminates in death.
MRI in patients shows specific bilateral necrosis in the head of the caudate nucleus and the putamen. Interestingly, they can be almost completely cured with the continuous administration of high doses of biotin, starting early in the disorder. In cases where this treatment is started later in the disease, some symptoms remain, such as residual paraparesis, mild mental retardation, and dystonia. To date, all patients diagnosed have been Arab in origin, having Saudi, Syrian, or Yemeni origin.
Joshi et al. (2002) carried out a retrospective analysis of all patients born with inborn errors of metabolism in Oman between June 1998 and December 2000. Among 82 patients, only one was diagnosed with biotin responsive basal ganglia disease [CTGA Database Editor's note: Computed annual incidence rate is 0.8/100,000].
Ozand et al. (1998) described a biotin-responsive basal ganglia disease in 10 patients, eight of whom were Saudi, one Syrian, and one of Yemeni origin. The parents in all cases were consanguineous, being first cousins in seven of the 10. In one family with first-cousin parents, two sisters were affected and four of their sibs, two boys and two girls, had died of a similar disease without diagnosis. Presentation ranged from 1 to 14 years. The disease appeared at onset as a subacute encephalopathy, with confusion, dysarthria, and dysphagia and occasional supranuclear facial nerve palsy or external ophthalmoplegia, and progressed to severe cogwheel rigidity, dystonia, and quadriparesis. These symptoms disappeared within a few days if biotin (5-10 mg/kg/day) was administered, and there were no neurologic sequela. Symptoms reappeared within one month if biotin was discontinued. Patients diagnosed late, or who had had repeat episodes, suffered from residual symptoms such as paraparesis, mild mental retardation, or dystonia. Biochemical studies of intermediary metabolism, autoimmune toxicologic studies, enzyme assays including those for biotinidase, carboxylase, and lysosomal activities, and bacterial and viral studies were all normal. The etiology was thought to be related to a defect in the transporter of biotin across the blood-brain barrier. The only consistent radiologic abnormality was central necrosis of the head of the caudate bilaterally and complete, or partial, involvement of the putamen on brain MRI. This finding was present during the initial acute encephalopathy and remained unchanged during follow-up of 3 to 10 years. Using linkage analysis in these four families, Zeng et al. (2005) mapped the genetic defect to 2q36.3 to a minimum candidate region of approximately 2 Mb on the basis of complete homozygosity.
[See: Saudi Arabia > Ozand et al., 1998; Zeng et al., 2005].