Adult onset hereditary spastic paraplegia

Gene: TRMT5

I don't know

Comment on list classification: There are at least 2 unrelated families with affected individuals harbouring biallelic TRMT5 variants, presenting with spastic paraparesis / spastic gait. However, spasticity is not the main presenting feature of this progressive syndrome. Based on available evidence, this gene can only be rated Amber for Adult onset hereditary spastic paraplegia.

Created: 18 Mar 2026, 11:38 a.m. | Last Modified: 18 Mar 2026, 11:38 a.m.

Panel Version: 6.9

PMID: 26189817 Powell et al., 2015
Subject 73901- lifelong exercise intolerance, presented at the age of 25 years with prolonged dyspnea associated with lactic acidosis, diagnosed with a mitochondrial myopathy associated with a marked histochemical and biochemical deficiency of COX and a defect in complex III activity. At 35 yrs showed hyperreflexia and extensor plantar reflexes with some clinical spasticity. Compound het for c.312_315del (p.Ile105Serfs∗4) frameshift and a c.872G>A (p.Arg291His).

PMID: 29021354 Tarnopolsky et al., 2017
P1 - 46yo female, presented at age 27 years with a lifelong history of exercise intolerance, muscle weakness, and shortness of breath on exertion. EMG normal at 27yo, progressive axonal sensory neuropathy seen at 43 years. 46yo - progression of proximal weakness with a waddling and spastic gait.
P2 (sister of P1) - presented at age 33 yrs with worsening gait and an increased frequency of falls; diagnosed with cerebral palsy in childhood; lower extremities: mild proximal and severe distal weakness/atrophy, severe spasticity, and upgoing toes; she showed gross motor, cognitive, and speech delays.
Both sisters compound het for TRMT5: c.872G>A (p.Arg291His) and c.312_315del (p.Ile105Serfs4X), confirmed in trans.

TRMT5 is associated with Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay, OMIM:616539 in OMIM (accessed 18 Mar 2026).
Sources: Literature

Created: 18 Mar 2026, 11:35 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay, OMIM:616539

Publications

• 26189817
• 29021354