Related Experiment Video
Updated: May 14, 2026
Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
Published on: October 3, 2018
The mild form of menkes disease: a 34 year progress report on the original case
M C Tchan1,2,3, B Wilcken4,5, J Christodoulou4,5
1Department of Genetic Medicine, Westmead Hospital, 2145, Sydney, Australia. michel.tchan@health.nsw.gov.au.
Abstract:
Classical Menkes disease is a neurodegenerative disorder caused by mutations in the copper-transporting ATPase ATP7A gene which, when untreated, is usually fatal in early childhood. A mild form of Menkes disease was originally reported in 1981 and clinical progress of the patient at 10 years described subsequently. The causative mutation is c.4085C>T in exon 21, causing an alanine to valine substitution in the highly conserved TM7 domain at the C-terminal end of the Menkes protein. Here we report his status at 34 years of age. Intellectual impairment is mild. Ataxia has nearly resolved but motor retardation, dysarthria and an extreme slow speech rate remain. In contrast to patients with the occipital horn syndrome, there have been no connective tissue complications of his mild Menkes disease. He has been under long-term copper therapy for more than 30 years and he continues to enjoy a good quality of life.
Insights
This study tracks a mild Menkes disease patient for 34 years, showing long-term copper therapy improves quality of life despite persistent neurological symptoms.
Area of Science:
- Genetics
- Neuroscience
- Biochemistry
Background:
- Menkes disease is a fatal neurodegenerative disorder due to ATP7A gene mutations.
- A mild form presents unique long-term progression characteristics.
- Previous reports detailed a patient's early clinical course and genetic mutation.
Purpose of the Study:
- To report the long-term clinical status of a mild Menkes disease patient at 34 years of age.
- To evaluate the sustained effects of copper therapy in a mild Menkes disease case.
- To compare the patient's long-term outcomes with classical Menkes disease and occipital horn syndrome.
Main Methods:
- Longitudinal clinical follow-up of a single patient.
- Genetic analysis identifying the specific ATP7A mutation (c.4085C>T).
- Assessment of neurological function, motor skills, and connective tissue status.
Main Results:
- The patient exhibits mild intellectual impairment and persistent motor deficits (dysarthria, slow speech).
- Ataxia has significantly improved over the 30+ year follow-up period.
- No connective tissue complications were observed, differentiating from occipital horn syndrome.
- Long-term copper therapy has maintained a good quality of life.
Conclusions:
- Mild Menkes disease can be managed with long-term copper therapy, leading to a good quality of life.
- Specific ATP7A mutations influence disease severity and long-term prognosis.
- Early diagnosis and sustained treatment are crucial for managing neurodegenerative copper metabolism disorders.
