Identification of a Novel ATP7A Variant in a Chinese Boy With Developmental Delay and Epilepsy
Abstract:
Menkes disease (MD) is a rare X-linked recessive syndrome that is caused by mutations in the ATP7A gene, which encodes the P-type ATP enzyme. The ATP7A gene encodes 1500 amino acids and is expressed in a number of organs, including the brain, muscles, kidneys and lungs. ATP7A transports copper between cell membranes using energy generated by ATP hydrolysis. Patients with the pathogenic variant in the ATP7A gene exhibit a distinctive pattern of severe neurodegeneration, which is often accompanied by specific alterations in hair morphology. The clinical manifestations of MD have been attributed to the dysfunction of copper-dependent enzymes. Here, we report a 7-month-old boy with MD associated with a novel variant of ATP7A (c.1965_1973del, p.Val656_Leu658del). Genetic testing revealed that both his mother and grandmother had identical ATP7A mutations, and we studied this family to better understand the natural history of this syndrome. In this article, we report for the first time the novel mutation in the ATP7A gene in a Chinese family. In our case, he suffers from simian line, developmental delay, epilepsy, hair changes (short, thin, thick, twisted, often light-coloured), decreased muscle tone, joint relaxation, brain vessel distortion, low serum copper, ceruloplasmin, elevated lactate and an abnormal EEG. Because of its rarity, MD is easily to be misdiagnosed.
Insights
Menkes disease (MD), a rare genetic disorder, is caused by ATP7A gene mutations affecting copper transport. This study identifies a novel ATP7A mutation in a Chinese family, highlighting diagnostic challenges.
Area of Science:
- Genetics
- Biochemistry
- Neuroscience
Background:
- Menkes disease (MD) is a rare, X-linked recessive disorder.
- It results from mutations in the ATP7A gene, crucial for copper transport.
- MD leads to neurodegeneration and characteristic hair abnormalities due to impaired copper-dependent enzyme function.
Purpose of the Study:
- To report a novel ATP7A gene mutation in a Chinese family with Menkes disease.
- To investigate the natural history of MD in this family.
- To emphasize the diagnostic challenges associated with this rare condition.
Main Methods:
- Clinical case study of a 7-month-old boy with suspected MD.
- Genetic analysis to identify ATP7A gene variants.
- Family-based study to trace the mutation's inheritance.
Main Results:
- Identification of a novel ATP7A mutation (c.1965_1973del, p.Val656_Leu658del) in the affected boy, his mother, and grandmother.
- Clinical presentation included developmental delay, epilepsy, abnormal hair, hypotonia, and neurological abnormalities.
- Biochemical findings revealed low serum copper and ceruloplasmin levels.
Conclusions:
- The novel ATP7A mutation expands the known spectrum of genetic variants causing Menkes disease.
- Early diagnosis is critical due to the potential for misdiagnosis.
- Understanding the natural history in affected families aids in better patient management.
