Autosomal recessive spastic paraplegia type 46

What it is

From: Orphanet

Autosomal recessive spastic paraplegia type 46 (SPG46) is a rare, complex type of hereditary spastic paraplegia characterized by an onset, in infancy or childhood, of the typical signs of spastic paraplegia (i.e. spastic gait and weakness of the lower limbs) associated with a variety of additional manifestations including upper limb spasticity and weakness, pseudobulbar dysarthria, bladder dysfunction, cerebellar ataxia, cataracts, and cognitive impairment that can progress to dementia. Brain imaging may show thinning of the corpus callosum and mild atrophy of the cerebrum and cerebellum. SPG46 is due to mutations in the GBA2 gene (9p13.2) encoding non-lysosomal glucosylceramidase.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Ataxia · Very frequent (99-80%)

Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).

Babinski sign · Very frequent (99-80%)

Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.

Cataract · Very frequent (99-80%)

A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Gait disturbance · Very frequent (99-80%)

The term gait disturbance can refer to any disruption of the ability to walk.

Lower limb spasticity · Very frequent (99-80%)

Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis.

Abnormal cerebral white matter morphology · Frequent (79-30%)

An abnormality of the cerebral white matter.

Cerebellar atrophy · Frequent (79-30%)

Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.

Cerebral atrophy · Frequent (79-30%)

Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.

Cerebral cortical atrophy · Frequent (79-30%)

Atrophy of the cortex of the cerebrum.

Cognitive impairment · Frequent (79-30%)

Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.

Corpus callosum atrophy · Frequent (79-30%)

The presence of atrophy (wasting) of the corpus callosum.

Abnormal pyramidal sign · Occasional (29-5%)

Functional neurological abnormalities related to dysfunction of the pyramidal tract.

Abnormal sperm morphology · Occasional (29-5%)

A structural anomaly of sperm.

Abnormal tendon morphology · Occasional (29-5%)

An abnormality of the structure or form of the tendons, also often called sinews.

Other findings in the same source

From: Orphanet

Additional reported features include Broad-based gait (Occasional (29-5%)); Decreased testicular size (Occasional (29-5%)); Dementia (Occasional (29-5%)); Head tremor (Occasional (29-5%)); Hearing impairment (Occasional (29-5%)); Hyperreflexia (Occasional (29-5%)); Impaired vibration sensation at ankles (Occasional (29-5%)); Nystagmus (Occasional (29-5%)); Peripheral axonal neuropathy (Occasional (29-5%)); Pes cavus (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Childhood; Infancy

Inheritance in the source

From: Orphanet

Autosomal recessive

Frequency and the population described

From: Orphanet

Reported case(s): 5.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Autosomal recessive spastic paraplegia type 46 is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Autosomal recessive spastic paraplegia type 46. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.