Transcript Ataxia in Children - Pune Ataxia Support Blog

B.S.Rao MD
Dept. of Pediatrics
S.Railway Hospital,
CHENNAI-600023, (INDIA)
ATAXIA
ACUTE
EPISODIC CHRONIC
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
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
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, CharcotMarie-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
Treatable causes of inherited ataxia
Refsum’s disease
Phytanic acid -hydroxylase deficiency
• Clinical features:
– Retinitis pigmentosa
– cardiomyopathy
– hypertrophic neuropathy
– Ichythiosis
• Treatment:
– Dietary restriction of Phytanic acid
Treatable causes of inherited ataxia
Bassen-Kornzweig syndrome
Abetalipoproteinemia
• Clinical features:
– Acanthocytosis
– Retinitis pigment
– Fat malabsorption
• Treatment:
– Vitamin E
Treatable causes of inherited ataxia
Wilson’s Disease
Copper accumulation
• Clinical features:
– Kayser-Fleischer ring
– Liver involvement
• Treatment:
– Chelators: Penicillamine, BAL , EDTA
Treatable causes of inherited ataxia
Hartnup’s disease
Tryptophan malabsorption
• Clinical features:
– Pellagra rash
– intermittent ataxia
• Treatment:
– Niacin
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
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
Treatable causes of inherited ataxia
Multiple Carboxylase Deficiency
Multiple carboxylase
deficiency:
Biotidinase deficiency
TREATMENT:
Clinical features:
Alopecia
recurrent infections
variable organic
aciduria
Biotin
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
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
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