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- A polyneuropathy that advances slowly over 10 years or more is almost invariably genetic in origin.
- The time of onset of these very chronic neuropathies is usually in early life but often cannot be dated with certainty by the patient or family.
- INFANTS: mistaken for muscular dystrophy or infantile muscular atrophy until sensory testing becomes possible.
- DEVELOPING CHILD: musculature naturally increases in power and volume with age, it may be difficult to decide whether the disease is progressive but
typically, there is trouble running or walking making it difficult to keep up with other children, repeated ankle injuries, toe catching,
labeled as clumsiness," or falls.
- Strongly indicative of one of these conditions at any age are pes cavus, hammertoes, and, in extreme forms, talipes equinus.
- ADULT: some of the inherited neuropathies are manifest as trophic changes of skin and bone in distal parts of the limbs indicate involvement of small
(pain) fibers and the presence of deformed and degenerated joints (Charcot joint)
- . The mutilating effects are the result repeated injury to analgesic parts and to a lack of autonomic vascular reflexes. Atrophy of muscle and trophic
changes in the skin are generally more marked than in the acquired forms of polyneuropathy.
- Charcot-MarieTooth (CMT) disease (type 1) shows slowed nerve conduction as a consequence of a disorder of myelin.
- A distinctive feature of hereditary neuropathy is the uniformity of the electrophysiologic changes, e.g., a similar degree of slowing of nerve
conduction velocity in all
the nerves, a feature that distinguishes this group from most acquired neuropathies.
- Demyelinating vs Axonal types of Inherited Neuropathies is based on the motor nerve (typically ulnar or median nerve) conduction velocities in the
arms
o Demyelinating category: slowing to velocities below 38 m/ s defines the demyelinating category.
INHERITED POLYNEUROPATHIES OF MIXED SENSORIMOTOR-AUTONOMIC TYPES
Description Features/Manifestations Diagnosis Treatment
HEREDITARY SENSORY AND Mutilating Hereditary Polyneuropathy in Begins with subtle loss of pain and PATHOLOGY:
AUTONOMIC NEUROPATHY Adults temperature sensation in the feet
TYPE I later of the fingers 1. Slowly progressive sensory distal
Autosomal Dominant Calluses, later blistering, ulceration of axonal degeneration and segmental
Onset: Second decade or later feet demyelination affecting non-
Osteomyelitis and osteolysis myelinated and small myelinated
also entails progressive, disabling, distal Shooting pain and sensory loss fibers
motor weakness, a consequence of Mild muscle weakness 2. Loss of function of enzyme serine
ongoing axonopathy and denervation Hypo/areflexia palmitoyl transferease (rate limiting
HSAN1 is a consequence of a loss of Loss of sweating step in biosynthesis of sphingolipids )
function of the enzyme serine Sensory nerve conduction: absent or
PROGNOSIS: Good
palmitoyltransferase, which is the slowed
ratelimiting step in the biosynthesis of
sphingolipids.
RECESSIVE MUTILATING Autosomal recessive Walking is delayed
SENSORY POLYNEUROPATHY Onset: Infancy and early childhood Ataxia
OF CHILDHOOD Ulceration of tips of toes and fingers
Some of the infantile hereditary sensory Areflexia
neuropathies are a result of a Impaired sensory modalities distal
disruption of molecular signaling part of the limbs but also over trunk
pathways for neurotropic Disruption of nerve growth factors
substances, such as nerve growth (Destruction of all sorts in the lower
factor, that are critical to neural extremities)
development
HSN II (MORVANS Autosomal recessive (Increase in size of Distal sensory deficit Prognosis: Poor; does not reach
SYNDROME, INFANTILE CENTRAL CANAL of spinal cord; Can adulthood
SYRINGOMYELIA, spread to the anterior part and affect
CONGENITAL SN) motor activity; If severe enough can
affect sensory part)
Onset: Infancy
HSN IV (CONGENITAL SN W/ Autosomal recessive High fever due to absence of
ANHYDROSIS / CONGENITAL Onset: infancy sweating mechanisms
INSENSITIVITY TO PAIN) Mental retardation
Short stature
Insensitivity to pain
Absence of neurons in dorsal root
ganglia, Lissauers tract and
decreased size of descending tract
of CN V (Patient has autonomic
dysfunctions. Patient may not
reach up to 5 years old)
HSN WITH FAMILIA Autosomal recessive Congenital absence of autonomic and HISTOPATHOLOGY: Diminished
DYSAUTONOMIA Ashkenazic Jewish families dorsal root ganglia sensory neurons myelinated and unmyelinated fibers,
(RILEY-DAY SYNDROME) Autonomic neuropathy (fluctuating and sympathetic and parasympathetic
Familial dysautonomia is usually body temperature, no tears, ganglion cells
manifested soon after birth: postural hypotension, dry mouth,
- poor sucking impaired taste sensation w/ PROGNOSIS: Poor (die at age 15 or
- failure to thrive strikingly smooth tongue, poor suck, below) due to autonomic dysfunction
- unexplained fever failure to thrive episodes of
- episodes of pneumonia TREATMENT: Symptomatic relief of GI
Later in life: neuropathy becomes pneumonia) symptoms and orthostatic fainting
overshadowed by other Main manifestations: Loss of pain and
manifestations of the disease, temperature sense with
notably repeated infections and preservation of pressure and tactile
abnormalities of the autonomic sense
nervous system Absent reflexes, hyporeflexia
Motor functions slightly affected
shown more effectively by reduced
motor conduction velocity in
peripheral nerves than it is by
weakness
Corneal ulceration, fixed pupils,
blotchiness of skin, excessive
sweating, difficulty in swallowing,
esophageal and intestinal dilatation,
emotional instability, recurrent
vomiting, stunted growth
NON-FAMILIAL SYSTEMIC primary (nonfamilial) systemic deposition Multiple myeloma Diagnosis - biopsy of sural nerve,
AMYLOIDOSIS of amyloid (termed AL), which is derived rectum / gum
from a circulating monoclonal protein Death cardiac or renal
Generalized symmetrical sensorimotor involvement by amyloid
neuropathy w/ serious autonomic
involvement
MANAGEMENT: high
doses of fat-soluble
vitamins & dietary fat
restrictions
FABRYS DISEASE (ANDERSON- -GALACTOSIDASE A Lipid deposition in all tissues and body fluids TREATMENT:
FABRY DSE., ANGIOKERATOMA DEFICIENCY Deposition of glycolipid (ceramide anticonvulsants
CORPORIS DIFFUSUM) X-linked recessive trihexodase) in nerves and cells of spinal (phenytion,
ganglia and anterior and intermediolateral carbamazepine,
horns of spinal cord gabapentine, amitriptline)
Heterozygous women (10%) have later onset for pain, enzyme
and milder neuropathic symptoms than men replacement therapy
DIAGNOSIS OF EARLY CHRONIC POLYNEUROPATHY DIAGNOSIS OF LATE CHRONIC DIAGNOSIS OF LATE CHRONIC
POLYNEUROPATHY POLYNEUROPATHY
SENSORIMOTOR PARALYSIS Diabetes Usually heredofamilial or CIDP
(LEGS>arms, DISTAL > Occult neoplasia sporadic mutations of Refsum disease
proximal) HIV infection genes Tangier disease
Paraproteinemia DNA testing is very Porphyria
Connective tissue helpful GBS
diseases Slowly progressive
CIDP Alcoholic-nutritional
polyneuropathy with CNS
Toxic neuropathies Toxic neuropathies
degeneration particularly
Vit. B deficiency / cerebellar ataxia is most
malnutrition
often hereditary