Child Neurology: Molybdenum cofactor deficiency

Abstract

Molybdenum cofactor deficiency (MoCD) is a rare inherited metabolic disorder characterized by neonatal onset intractable seizures, severe psychomotor retardation, dysmorphic facies, and dislocated ocular lenses.1 A characteristic biochemical profile permits early diagnosis. Although more than 100 genetically characterized patients have been reported, this number is discrepant with the actual prevalence as MoCD is often mistaken for hypoxic-ischemic encephalopathy (HIE) secondary to perinatal asphyxia. It is important to recognize MoCD to provide appropriate genetic counseling and prenatal diagnosis.2 Effective pharmacotherapies that overcome the primary biochemical defect are also in the pipeline. We present a child with biochemically and genetically confirmed MoCD and discuss the clinical, imaging, biochemical, and genetic profile of this disorder.CASE REPORT A 4-year-old boy from the south Indian state of Kerala presented with developmental delay and seizures. He was the only child of consanguineous parents (first cousins). He was born at term following an uneventful antenatal period with a birthweight of 3.25 kg, cried immediately at birth, and did not have features of birth asphyxia. He developed generalized seizures on the fifth day of life. The seizures remained refractory to multiple anticonvulsants at optimal dosages. He also developed episodes of intermittent sudden flexion of trunk and limbs once in 1-2 minutes. The frequency of these episodes was reduced with time and occurred in response to sound only. Since 6 months of age, he developed progressive stiffness with intermittent posturing of neck and trunk. There was no history of neurologic illness in the family.On examination, he was irritable and poorly nourished with intermittent stridor. He had microcephaly with head circumference of 46 cm, bilaterally dislocated lenses, and could not fix or track light. He had exaggerated startle to sound. There was severe spasticity, cervical dystonia, and opisthotonus. Investigations showed normal hemogram, renal and hepatic function tests, serum vitamin B 12 , folic acid, and biotidinase levels. Cytogenetic study showed normal male karyotype. Screening for amino-acidemias, organic acidemias, and disorders of fatty acid oxidation by tandem mass spectrometry drew negative results. Urine analysis for abnormal metabolites, glycosaminoglycans, total mucopolysaccharides, and organic acids was normal. Lactate (32.9 mg/dL; ref 4.5-20 mg/dL) and ammonia (67.7 mg/dL; ref 11-35 mg/dL) were mildly elevated. Mild laryngomalacia was detected on bronchoscopic examination. Brain MRI done at fourth month of life showed severe diffuse cerebral atrophy, areas of T2 shortening in bilateral basal ganglia suggestive of intracranial haemorrhage, and pontine hypoplasia with enlargement of the prepontine cistern ( figure, A-D). EEG showed recurrent multifocal epileptiform discharges.Serum homocysteine was markedly reduced (0.9 mmol/L; ref 4-12 mmol/L), and uric acid was undetectable. Examination of purine metabolites in urine showed the

The Persistent Generalized Muscle Contraction in Siblings with Molybdenum Cofactor Deficiency Type A

“…The MRI findings of MoCD are apparently similar to those of hypoxicischemic injury (HIE) as they exhibit extensive edematous lesions in the cerebrum and the basal ganglia. 7 The pattern of widespread restricted diffusion involving the depths of sulci with sparing of the peripheral cortex is fairly distinctive for MoCD. Restricted diffusion involving the depths of sulci can occur in mild perinatal HIE as well; however, when this pattern occurs in HIE, the affected deep cortex tends to be localized to watershed territories, as opposed to MoCD where the cortical involvement is much more widespread.…”

“…In previous reports, the motor symptoms of MoCD are described variously as dystonia, spasticity, and hyperkinesis. 4,7,8 Dystonia is defined as abnormal, often repetitive movements or postures that are caused by sustained or intermittent muscle contraction. Dystonic movements tend to be initiated or worsened by voluntary action.…”

“…Restricted diffusion involving the depths of sulci can occur in mild perinatal HIE as well; however, when this pattern occurs in HIE, the affected deep cortex tends to be localized to watershed territories, as opposed to MoCD where the cortical involvement is much more widespread. 7,8,13 The caudate nucleus is rarely affected in HIE and is always affected in MoCD. The symmetrical pallidum is damaged easily in MoCD, and more diffusely in HIE.…”

Diffic ulties of diagnostics of epilepsy due to mol ybdenum cofactor deficienc y: a case report

“…Дефицит кофактора молибдена является тяжелым наследственным аутосомно-рецессивным неонатальным метаболическим заболеванием, которое вызывает рефрактерные к терапии эпилептические приступы, черепные дизморфии, выраженное нервно-психическое недоразвитие и зачастую приводит к ранней смерти [1,4]. Клинические симптомы и данные нейровизуализации могут напоминать признаки, характерные для гипоксически-ишемической энцефалопатии новорожденных, что нередко приводит к диагностическим ошибкам [6,7].…”

“…Основные этапы биосинтетического пути кофактора молибдена представлены на рис. 1 [6]. Основываясь на этих 3 основных стадиях, дефицит кофактора молибдена подразделяют на 3 типа: A, B и C, обусловленные соответственно мутациями генов MOCS1, MOCS2 и Gephyrin (см.…”