B.S.Rao MDDept. of PediatricsS.Railway Hospital,

CHENNAI-600023, (INDIA)

ACUTE EPISO DIC CHRO NIC

ATAXIA

CAUSES OF ATAXIA : ACUTE

• Idiopathic

• Metabolic:

– Hypoglycemia

– Hyponatremia

– Hyperammonemia

– Leigh’s disease

– Wernicke’s encephalopathy

Causes of Ataxia : ACUTE

• Infections:

– Bacterial meningitis

– Viral meningitis

– Brain stem encephalitis

• Toxins

• Hydrocephalus

• Cerebellar lesions

• Neuroblastoma

• Hypotonia

• Pendular reflexes

• Limb movement impairment

– Asthenia

– Ataxia

– Decompensation of movements

– Asynergia

– Tremor

– Deviation from line of movement

Findings in cerebellar disease

• Impaired rebound

• Dysdiadochokinesia

• Static tremor

• Vertigo

• Dysarthria

• Nystagmus

• Gait difficulties

Causes of Ataxia : ACUTE

• Polyradiculopathy

– Guillain - Barre syndrome

– Tick paralysis

• Labrynthitis

• Brain stem tumors

• Multiple sclerosis

• Trauma

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

– Refsum’s

– Porphyria

Causes of ataxia : CHRONIC• Fixed deficit : CP , Malformations

• Degenerative:– Friedreich’s ,Dominant hereditary ataxia, Charcot-

Marie-Tooth disease, Roussy-Levy

• Other inherited diseases:– Wilson’s , Refsum’s, Bassen-Kornweig – Ataxia telengiectasia, Sphingolipidoses– Neuronal ceroid-lipofuscinoses– Chediak Higashi, von Hippel-Lindau disease

Causes of ataxia :CHRONIC

• Acquired diseases:

– Hypothyroidism

– Neoplasms

– Drugs and toxins

– Multiple sclerosis

– Nutritional cerebellar degenerations

Phytanic acid -hydroxylase deficiency• Clinical features:

– Retinitis pigmentosa– cardiomyopathy– hypertrophic neuropathy– Ichythiosis

• Treatment:– Dietary restriction of Phytanic acid

Treatable causes of inherited ataxia Refsum’s disease

Abetalipoproteinemia

• Clinical features:

– Acanthocytosis

– Retinitis pigment

– Fat malabsorption

• Treatment:– Vitamin E

Treatable causes of inherited ataxia Bassen-Kornzweig syndrome

Copper accumulation

• Clinical features:– Kayser-Fleischer ring– Liver involvement

• Treatment:– Chelators: Penicillamine, BAL , EDTA

Treatable causes of inherited ataxia Wilson’s Disease

Tryptophan malabsorption• Clinical features:

– Pellagra rash– intermittent ataxia

• Treatment:– Niacin

Treatable causes of inherited ataxia Hartnup’s disease

Familial Periodic Ataxia :

Cause not known

Clinical features:• Episodic attacks• Worst with

pregnancy or birth control pills

TREATMENT: Acetazolamide

Treatable causes of inherited ataxia Familial Periodic Ataxia

Urea cycle defects: Urea cycle enzyme defects

Clinical features:Hyper ammonemia

TREATMENT: Protein restriction Arginine , benzoate , alfa-ketoacids

Treatable causes of inherited ataxia Urea Cycle Defects

Multiple carboxylase

deficiency:

Biotidinase deficiency

Clinical features:Alopeciarecurrent infectionsvariable organic

aciduria

TREATMENT: Biotin

Treatable causes of inherited ataxia Multiple Carboxylase Deficiency

Friedreich’s ataxia:Clinical 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

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

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

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

Biotin deficiency:Clinical 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

Biotin deficiency: Lab findings

• Metabolic acidosis

• specific organic aciduria :

– 3 methyl - crotonylglycine

– 3 hydroxyisovaleric acid

– 3 hydroxypropinic acid, and

– 2 methylcitric acid

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

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.

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

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

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

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

• 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

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

Pathophysiology: