Handbook of Pediatric Electroencephalography by Veena Kander now on ICNApedia VLE

CNS degenerative disorders of infancy

CNS degenerative disorders of infancy

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DiseaseEnzyme Defect and GeneticsOnsetEarly ManifestationsVision and HearingSomatic FindingsMotor FindingsSeizuresLabsClinical Course
White matter
Globoid (Krabbe) leukodystrophy Recessive galactocerebroside β-galactosidase deficiency. Chromosome 14q21–14q31 Infantile form first 6 mo. Late-onset form 2–6 y. Adolescent and adult forms are rare

Feeding difficulties

Shrill cry

Irritability

Arching of back

Optic atrophy

Hyperacusis occasionally

Underweight

Microcephaly

Spasticity

Earlier hypotonia

Decerebrate posturing

Myoclonic Generalized Elevated CSF protein, prolonged sural nerve conduction, enzyme deficiency in leukocytes, cultured skin fibroblasts. Demyleination and gliosis on MRI and CT.

Rapid. Death usually by 1.5–2 y.

Late-onset cases may live 5–10 y.

Hematopoietic stem cell transplantation and enzyme replacement therapy is an experimental.

Metachromatic leukodystrophy Recessive Arylsulfatase A (ASA) deficiency 22q13 Variant: Saposin B deficiency Infantile form at 18–24 mo Juvenile and adult forms Incoordination, gait disturbance, general regression. Optic atrophy Macrocephaly in infantile form

Upper and lower motor neuron signs

Ataxia

Infrequent CSF protein elevated. Urine sulfatide increased. Enzyme deficiency in leukocytes and fibroblasts. Imaging: diffuse white matter

Moderately slow.

Infantile form death by 3–8 y.

Juvenile form death by 10–15 y. Hematopoietic stem cell transplantation is an experimental treatment

Pantothenate kinase–associated neurodegeneration (Hallervorden-Spatz syndrome)

AR

Most common chromosome 20 PANK2 gene

Age 10 y Rigidity, dystonia, gait disturbance, tremor Retinal degeneration.   Extrapyramidal signs, dysarthria, hyperreflexia Variable Axonal degeneration (spheroids). Iron deposits in basal ganglia on MRI: eye-of-the-tiger appearance Progressive mental/motor deterioration
Pelizaeus-Merzbacher disease X-linked recessive; rare female. Proteolipid protein (myelin) decreased. Xq22. Birth (perinatal) to 2 y. Eye rolling often shortly after birth. Head bobbing. Slow loss of intellect. Slowly developing optic atrophy. Hearing normal. Nystagmus. Head and body normal.

Cerebellar signs Spasticity

Hyperreflexia

Usually only late

None specific

Point mutations or duplications of PLP gene account for 65%–90% of cases.

Very slow
Diffuse, but primarily gray matter
Poliodystrophy (Alpers disease)

Recessive

Metabolic forms

Infancy to adolescence Variable: regression, seizures, incoordination, hepatic failure Cortical blindness and deafness  

Incoordination

Spasticity

Myoclonic, akinetic, and generalized

POLG1 and mitochondrial mutations

Liver steatosis and cirrhosis

Muscle and liver biopsy

Rapid with death within 1–3 y after onset

Variants in older children, adults

Tay-Sachs disease and GM2 gangliosidosis variants: Sandhoff disease; juvenile; chronic-adult

AR Hexosaminidase deficiencies caused by HEXA gene on chromosome 15q23–24.62,63.

Sandhoff hexosaminidase A and B deficiency Juvenile partial hexosaminidase A.

Tay-Sachs and Sandhoff 3–6 mo

Others 2 y or later.

Variable: shrill cry, vision loss, infantile spasms, developmental arrest.

In juvenile and chronic forms: motor and mental difficulties

Cherry-red macula

Blindness

Hyperacusis

Juvenile form: Strabismus and late blindness

 

Early hypotonia. Late decerebrate rigidity.

Juvenile and chronic forms: dysarthria, ataxia, spasticity

Infantile spasms and generalized.

Blood smear: vacuolated lymphocytes; basophilic hypergranulation.

Enzyme deficiencies in leukocytes and fibroblasts. Imaging: abnormal thalami and white matter

Moderately rapid. Death usually by 2–5 y. In juvenile form, 5–15 y.
Niemann-Pick disease and variants

AR

Sphingomyelinase deficiency in types A and C

First 6 mo

In variants onset later often non-Jewish.

Slow development

Protruding belly

Cherry-red macula in 35%–50%. Blindness

Deafness

 

Early hypotonia

Late spasticity

Extrapyramidal signs

Ataxia

Rare and late

Vacuolated lymphocytes

X-rays: "mottled" lungs, decalcified bones

Leukocyte and fibroblast enzyme deficiency

Moderately slow

Death usually by 3–5 y

Infantile Gaucher disease (glucosylceramide lipidosis) AR First 6 mo Stridor or hoarse cry Feeding difficulties. Cherry red macula. Convergent squint. Deafness   Early opisthotonos followed by decerebrate rigidity Rare and late Anemia X-rays: thinned cortex, trabeculation of bones. "Gaucher cells" in bone marrow. Leukocytes or fibroblasts enzyme deficiency Rapid Experimental enzyme replacement therapy
Generalized gangliosidosis and juvenile type (GM1 gangliosidoses)

AR

β-galactosidase

Infantile: first 6 mo

Late infantile: 7 mo to 3 y

Juvenile onset

Developmental arrest Protruding belly

Coarse facies Juvenile form: ataxia and dysarthria

50% "cherry-red spot." Corneal clouding

Juvenile: retinitis pigmentosa

Macrocephaly

Hepatosplenomegaly

Gingival hypertrophy Cardiomyopathy

Early hypotonia

Later spasticity

Late Vacuolated lymphocytes. X-rays: dorsolumbar kyphosis, "breaking" of vertebrae.

Rapid within a few years

Slower in juvenile type

Subacute necrotizing encephalomyelopathy (Leigh disease) Variable: pyruvate carboxylase, pyruvate dehydrogenase, cytochrome enzymes, mitochondrial DNA. Infancy to late childhood

Feeding difficulties

Feeble or absent cry

Hypotonia

Apnea

Developmental regression

Ataxia

Optic atrophy

Roving eye movements

Ophthalmoplegia

Head usually normal. Cardiac and renal tubular dysfunction

Flaccid hypotonia

Later spasticity

Ataxia

Myelopathy

Rare

Tonic

Increased CSF and blood lactate and pyruvate. High-signal MRI T2 foci in thalami and basal ganglia. DNA and enzyme tests on muscle

Usually rapid

Central hypoventilation a frequent cause of death

Menkes disease (kinky hair disease)

X-linked

Defect in copper absorption

Infancy

Peculiar facies

White, twisted and split hair

Hypothermia

Optic disk pallor and micro-cysts of pigment epithelium Growth retardation Variable: floppy to spastic

Myoclonic infantile spasms

Status epilepticus

Cerebral angiography shows elongated arteries. Copper and ceruloplasmin low

Moderately rapid

Death usually by 3–4 y

Carbohydrate-deficient glycoprotein syndrome

AR

Glycoprotein abnormality

Infancy Failure to thrive, retardation, protein-losing enteropathy

Strabismus

Retinopathy

Dysmorphic facies

Prominent fat pads

Inverted nipples

Variable hypotonia

Neuropathy

Rare

Normal transferrin decreased

Carbohydrate-deficient transferrin increased

Liver steatosis

Cerebellar hypoplasia

Cardiomyopathy

Thrombosis

Hepatic fibrosis

Abetalipoproteinemia (Bassen-Kornzweig disease)

AR

Microsomal triglyceride transfer protein (MTP) on chr 4q22–24

Early childhood Diarrhea in infancy

Retinitis pigmentosa

Ophthalmoplegia

None

Ataxia

Movement disorder

None

Abetalipoproteinemia: acanthocytosis, low serum vitamin E

Cerebellar atrophy

Progression arrested with vitamin E

AR, autosomal recessive; CNS, central nervous system; CSF, cerebrospinal fluid; CT, computed tomography; EEG, electroencephalogram; ERG, electroretinogram; MRI, magnetic resonance imaging; WBC, white blood cell.

http://icnapedia.org/wiki/neurolists/cns-degenerative-disorders-of-infancy
APA Style
CNS degenerative disorders of infancy. (n.d.). In ICNApedia. Retrieved May 22,2017 16:19:40 from http://icnapedia.org/wiki/neurolists/cns-degenerative-disorders-of-infancy
MLA Style
"CNS degenerative disorders of infancy." ICNApedia: The Child Neurology Knowledge Environment, Inc. October 14, 2015. Web. May 22,2017 16:19:40
AMA Style
ICNApedia contributors. CNS degenerative disorders of infancy. ICNApedia, The Child Neurology Knowledge Environment. October 14, 2015. Available at: http://icnapedia.org/wiki/neurolists/cns-degenerative-disorders-of-infancy.Accessed May 22,2017 16:19:40.

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