Hereditary sensory neuropathy type I.

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Hereditary sensory neuropathy type I.

Auer-Grumbach M.

ABSTRACT: Hereditary sensory neuropathy type I (HSN I) is a slowly

progressive neurological disorder characterised by prominent

predominantly distal sensory loss, autonomic disturbances, autosomal

dominant inheritance, and juvenile or adulthood disease onset. The

exact prevalence is unknown, but is estimated as very low. Disease

onset varies between the 2nd and 5th decade of life.

The main clinical feature of HSN I is the reduction of sensation

sense mainly distributed to the distal parts of the upper and lower

limbs. Variable distal muscle weakness and wasting, and chronic skin

ulcers are characteristic. Autonomic features (usually sweating

disturbances) are invariably observed. Serious and common

complications are spontaneous fractures, osteomyelitis and necrosis,

as well as neuropathic arthropathy which may even necessitate

amputations. Some patients suffer from severe pain attacks. Hypacusis

or deafness, or cough and gastrooesophageal reflux have been observed

in rare cases.

HSN I is a genetically heterogenous condition with three loci and

mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis

is based on the clinical observation and is supported by a family

history. Nerve conduction studies confirm a sensory and motor

neuropathy predominantly affecting the lower limbs. Radiological

studies, including magnetic resonance imaging, are useful when bone

infections or necrosis are suspected. Definitive diagnosis is based

on the detection of mutations by direct sequencing of the SPTLC1 and

RAB7 genes.

Correct clinical assessment and genetic confirmation of the diagnosis

are important for appropriate genetic counselling and prognosis.

Differential diagnosis includes the other hereditary sensory and

autonomic neuropathies (HSAN), especially HSAN II, as well as

diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by

other neurotoxins / drugs, immune mediated neuropathy, amyloidosis,

spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying

skin tumours like amelanotic melanoma.

Management of HSN I follows the guidelines given for diabetic foot

care (removal of pressure to the ulcer and eradication of infection,

followed by the use of specific protective footwear) and starts with

early and accurate counselling of patients about risk factors for

developing foot ulcerations. The disorder is slowly progressive and

does not influence life expectancy but is often severely disabling

after a long duration of the disease.