Ataxia in Children

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Ataxia in Children
B.S.Rao MD Dept. of Pediatrics S.Railway
Hospital, CHENNAI-600023, (INDIA)
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CAUSES OF ATAXIA ACUTE

• Idiopathic
• Metabolic
• Hypoglycemia
• Hyponatremia
• Hyperammonemia
• Leighs disease
• Wernickes encephalopathy

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Causes of Ataxia ACUTE

• Infections
• Bacterial meningitis
• Viral meningitis
• Brain stem encephalitis

• Toxins
• Hydrocephalus
• Cerebellar lesions
• Neuroblastoma

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Findings in cerebellar disease

• Hypotonia
• Pendular reflexes
• Limb movement impairment
• Asthenia
• Ataxia
• Decompensation of movements
• Asynergia
• Tremor
• Deviation from line of movement

• Impaired rebound
• Dysdiadochokinesia
• Static tremor
• Vertigo
• Dysarthria
• Nystagmus
• Gait difficulties

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Causes of Ataxia ACUTE

• Polyradiculopathy
• Guillain - Barre syndrome
• Tick paralysis
• Labrynthitis
• Brain stem tumors
• Multiple sclerosis
• Trauma

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Causes of Ataxia EPISODIC

• Basilar artery migraine (benign paroxysmal
  vertigo)
• Epilepsy
• Postictal state
• Minor motor status
• Toxins
• Dominant paroxysmal ataxia

• Metabolic
• Hypoglycemia
• Hyperammonemia
• Organic acid disorders , Maple syrup
• Hartnup ,hyperpyruvic acidemia
• Refsums
• Porphyria

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Causes of ataxia CHRONIC

• Fixed deficit CP , Malformations
• Degenerative
• Friedreichs ,Dominant hereditary ataxia,
  Charcot-Marie-Tooth disease, Roussy-Levy
• Other inherited diseases
• Wilsons , Refsums, Bassen-Kornweig
• Ataxia telengiectasia, Sphingolipidoses
• Neuronal ceroid-lipofuscinoses
• Chediak Higashi, von Hippel-Lindau disease

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Causes of ataxia CHRONIC

• Acquired diseases
• Hypothyroidism
• Neoplasms
• Drugs and toxins
• Multiple sclerosis
• Nutritional cerebellar degenerations

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Treatable causes of inherited ataxia Refsums
disease

• Phytanic acid ?-hydroxylase deficiency
• Clinical features
• Retinitis pigmentosa
• cardiomyopathy
• hypertrophic neuropathy
• Ichythiosis
• Treatment
• Dietary restriction of Phytanic acid

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Treatable causes of inherited ataxia
Bassen-Kornzweig syndrome

• Abetalipoproteinemia
• Clinical features
• Acanthocytosis
• Retinitis pigment
• Fat malabsorption
• Treatment
• Vitamin E

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Treatable causes of inherited ataxia Wilsons
Disease

• Copper accumulation
• Clinical features
• Kayser-Fleischer ring
• Liver involvement
• Treatment
• Chelators Penicillamine, BAL , EDTA

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Treatable causes of inherited ataxia Hartnups
disease

• Tryptophan malabsorption
• Clinical features
• Pellagra rash
• intermittent ataxia
• Treatment
• Niacin

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Treatable causes of inherited ataxia Familial
Periodic Ataxia
Familial Periodic Ataxia Cause not known

• Clinical features
• Episodic attacks
• Worst with pregnancy or birth control pills

TREATMENT Acetazolamide
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Treatable causes of inherited ataxia Urea Cycle
Defects
Urea cycle defects Urea cycle enzyme defects
Clinical features Hyper ammonemia
TREATMENT Protein restriction Arginine ,
benzoate , alfa-ketoacids
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Treatable causes of inherited ataxia Multiple
Carboxylase Deficiency
Multiple carboxylase deficiency Biotidinase
deficiency
Clinical features Alopecia recurrent
infections variable organic aciduria
TREATMENT Biotin
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Friedreichs ataxiaClinical features

• AR inheritance
• Onset before puberty of gait ataxia or scoliosis
• Rapid progression in initial 2 yr of
• Limb ataxia ,scoliosis,loss of DTR
• position and light touch sensation
• Cardiomyopathy
• Absence of ophthalmoplegia dementia

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Biotin (Vitamin H)

• Biotin is a cofactor for 4 carboxylation enzymes
• these enzymes are involved in carbon chain
  elongation reactions Gluconeo- genesis ,fatty
  acid synthesis, leucine catabolism etc.
• Biotin is present in low conc. in several foods
  - intestinal synthesis serves as a major source

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Biotin (Vitamin H)

• The enzyme biotidinase cleaves Biotin biotin
  from biocytin(biotin - lysine) -thus allowing
  biotin reuse
• Recommended daily intake
• 35 microgram for neonates
• 100-200 for adults

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Biotin deficiency

• Deficiency from inadequate dietary intake is
  quite rare - reported in 2 children on large
  quantities of raw albumin (avidin binds biotin)
• has been reported as a consequence of
  hyperalimentation and chronic hemodialysis

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Biotin deficiencyClinical features

• Generalized scaly erythematous rash resembling
  seborrhoea
• alopecia totalis
• anorexia , metabolic acidosis
• developmental delay ,seizures , progressive
  ataxia and hearing loss
• In neonates infants may progress rapidly -with
  vomiting ,FTT , hypotonia , severe met.acidosis
  to coma

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Biotin deficiency Lab findings

• Metabolic acidosis
• specific organic aciduria
• 3 methyl - crotonylglycine
• 3 hydroxyisovaleric acid
• 3 hydroxypropinic acid, and
• 2 methylcitric acid

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Biotin dependency

• Biotin-dependent Propionic acidemia
• deficiency of the enzyme Propionyl CoA
  carboxylase (Biotin essential cofactor)
• Clinical features
• rapid onset of an overwhelming illness with
  severe vomiting and dehydration leading to
  lethargy and coma
• may appear first in neonatal period or infancy
  precipitated by febrile illness

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Biotin dependency management

• Dietary therapy with restriction of intake of
  Leucine ,valine, threonine , and methionine
• Biotin 5 mg bid
• Acute episodes Fluid therapy , electrolytes ,
  glucose and supplementary proteins to prevent
  tissue breakdown , PD, exchange Tr.

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Biotin dependent holocarboxylase synthetase
deficiency(multiple carboxylase eficiency)

• Neonatal Vomiting ,lethargy ,hypotonia
  associated with ketoacidosis, lactic acidosis ,
  and organic aciduria in first few days of life
• Result of the deficiency of the enzyme
  Holocarboxylase synthetase- the enzyme that
  attaches Biotin to various carboxylases
• Most improve dramatically following oral
  administration of Biotin 10mg/ day

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Biotinidase deficiency Late onset Multiple
carboxylase deficiency

• Clinical manifestations by 2 - 3 months
• seizure, episodic ataxia, hyperventilation,
  hearing loss, optic atrophy, developmental delay,
  skin rash, candidiasis, conjunctivitis
• Laboratory
• lactic acidosis, hyperammonemia, organic
  aciduria, decreased B and T cell activity
• Except for visual hearing loss - responds to
  Biotin 10mg/day

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Ataxia telangiectasia(Louis-Bar)

• neurological, cutaneous, hepatic, skin,
  immunological endocrinological abnormalities
• Telangiectasias develop around 3yr of age
• Bulbar conjunctivae, nasal bridge, malar areas ,
  ext. ears, hard palate, upper chest, antecubital
  fossa
• Cutaneous stigmata café au lait spots,
  premature graying of hairs, sclerodermatous
  changes

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Clinical features

• Progressive cerebellar ataxia
• oculocutaneous telangiectasia
• chronic sinupulmonary infections
• high incidence of malignancy
• variable humoral cellular immunedeficiency
• Ataxia begins soon after child begins to walk

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Pathophysiology

• Patients cells have
• increased sensitiveness to ionizing radiation
• defective DNA repair
• frequent chrosomal abnormalities
• Chromosomal breakages in Ch 7 and 14 , genes
  coding for T-cell receptor Ig heavy chains
• Malignancies reported lymphoreticular type

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Pathophysiology

• Humoral immunoglobulin abnormality
• absence of IgA (50-80)
• Lymphocyte function is generally depressed
• AR inheritance
• Genetics abnormal gene mapped out to the long
  arm of chromosome 11