Rare Pulmonology News

Disease Profile

Menkes disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

E83.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Menkes syndrome; Steely hair disease; Menkea syndrome;

Categories

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders;

Summary

Menkes disease (MD) is an inherited condition that impacts the way the body processes copper levels in the body. MD primarily affects the nervous system and connective tissue with symptoms that tend to get worse over time. Symptoms of MD usually appear within the first few months of life and include sparse, kinky hair; slow growth (failure to thrive); and seizures. Additional features may include low muscle tone (hypotonia), sagging facial features, and developmental and intellectual disability. Most children with MD have severe symptoms that lead to death at an early age. Occipital horn syndrome is a less severe form of MD that begins in early to middle childhood. The adult-onset form is the least severe and primarily impacts the nerves and muscles. MD is caused by alterations (mutations) in the ATP7A gene and is inherited in an X-linked recessive pattern. MD mainly affects boys. Early treatment with copper may improve the long-term outcome in some children with this disease.[1][2]

Symptoms

Symptoms of Menkes disease (MD) begin shortly after birth and may vary from person to person. Early signs and symptoms may include:[1][2][3]

  • Progressive nervous system decline
  • Seizures
  • Kinky, light colored, easily breakable hair
  • Low muscle tone (hypotonia)
  • Twisted blood vessels (arterial tortuosities)
  • Characteristic facial features
  • Bladder sacs or pouches (diverticula)

A milder form of the disease, called the occipital horn syndrome or X-linked cutis laxa, is characterized by loose skin and joints, bony growths at the back of the skull, twisted blood vessels and bladder problems. Symptoms of occipital horn syndrome typically begin in childhood.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal palate morphology
Abnormality of the palate
Abnormality of the roof of the mouth

[ more ]

0000174
Aplasia/Hypoplasia of the abdominal wall musculature
Absent/small abdominal wall muscles
Absent/underdeveloped abdominal wall muscles

[ more ]

0010318
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Dry skin
0000958
Fatigue
Tired
Tiredness

[ more ]

0012378
Feeding difficulties in infancy
0008872
Hyperextensible skin
Hyperelastic skin
Skin hyperelasticity
Stretchable skin

[ more ]

0000974
Hypopigmentation of hair
Loss of hair color
0005599
Inguinal hernia
0000023
Intracranial hemorrhage
Bleeding within the skull
0002170
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Muscular hypotonia
Low or weak muscle tone
0001252
Pectus excavatum
Funnel chest
0000767
Seizure
0001250
Sparse hair
0008070
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Umbilical hernia
0001537
Vascular dilatation
Wider than typical opening or gap
0002617
Woolly hair
Kinked hair
0002224
30%-79% of people have these symptoms
Abnormal carotid artery morphology
0005344
Abnormality of the metaphysis
Abnormality of the wide portion of a long bone
0000944
Arterial stenosis
Narrowing of an artery
0100545
Atypical scarring of skin
Atypical scarring
0000987
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances

[ more ]

0000708
Exostoses
Formation of new noncancerous bone on top of existing bone
0100777
Full cheeks
Apple cheeks
Big cheeks
Increased size of cheeks
Large cheeks

[ more ]

0000293
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Malabsorption
Intestinal malabsorption
0002024
Mask-like facies
Expressionless face
Lack of facial expression
Mask-like facial appearance

[ more ]

0000298
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Muscle weakness
Muscular weakness
0001324
Narrow chest
Low chest circumference
Narrow shoulders

[ more ]

0000774
Nausea and vomiting
0002017
Prolonged neonatal jaundice
Prolonged yellowing of skin in newborn
0006579
Prominent occiput
Prominent back of the skull
Prominent posterior skull

[ more ]

0000269
Thickened skin
Thick skin
0001072
Venous insufficiency
Poorly functioning veins
0005293
Wormian bones
Extra bones within cranial sutures
0002645
5%-29% of people have these symptoms
Bladder diverticulum
0000015
Bowing of the long bones
Bowed long bones
Bowing of long bones

[ more ]

0006487
Chondrocalcinosis
Calcium deposits in joints
0000934
Chorea
0002072
Gastrointestinal hemorrhage
Gastrointestinal bleeding
0002239
Hypoglycemia
Low blood sugar
0001943
Hypothermia
Abnormally low body temperature
0002045
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Osteomyelitis
Bone infection
0002754
Osteoporosis
0000939
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures

[ more ]

0002757
Sepsis
Infection in blood stream
0100806
Spontaneous hematomas
0007420
Tarsal synostosis
Fused ankle bones
0008368
Percent of people who have these symptoms is not available through HPO
Abnormality of the face
Abnormal face
Facial abnormality

[ more ]

0000271
Brachycephaly
Short and broad skull
0000248

Cause

Menkes disease is caused by genetic alterations in the ATP7A gene.[1]

Diagnosis

Menkes disease is typically diagnosed based on the clinical features, medical examination, and genetic testing for alterations in the ATP7A gene. Other types of tests that may be helpful include analysis of catecholamines (chemicals that are sensitive to copper) and copper levels in the blood.[2]

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    There is no specific treatment for Menkes disease (MD). Some boys with MD respond to early treatment (started in the first weeks of life) with copper complexes (mainly copper-histidine). This treatment may prevent or slow nervous system damage, decrease the number of seizures, and increase lifespan. Copper treatment does not work for all patients with MD. Other treatments are aimed at preventing and/or managing the symptoms and complications associated with this condition. These may include:[2][3]

    Some of the specialists who might be involved in the care of someone with Menkes disease include:[1][2]

    • Neurologist
    • Gastroenterologist
    • Developmental specialist
    • Urologist
    • Genetics professional

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          Genetics of Menkes Kinky Hair Disease
          Menkes Disease (Neurology)
          Dermatologic Manifestations of Menkes Kinky Hair Disease
        • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Menkes disease. Click on the link to view a sample search on this topic.

          References

          1. Kaler S. ATP7A-Related Copper Transport Disorders. GeneReviews. Updated Aug. 18, 2016; https://www.ncbi.nlm.nih.gov/books/NBK1413.
          2. Vairo FPE, Chwal BC, Perini S, Ferreira MAP, de Freitas Lopes AC, Saute JAM. A systematic review and evidence-based guideline for diagnosis and treatment of Menkes disease. Mol Genet Metab. Jan 2019; 126(1):6-13. https://pubmed.ncbi.nlm.nih.gov/30594472.
          3. Kim MY, Kim JH ,Cho MH ,Choi YH, Kim SH, Im YJ, et al. Urological Problems in Patients with Menkes Disease. J Korean Med Sci. Jan 7, 2019; 34(1):e4. https://pubmed.ncbi.nlm.nih.gov/30618512.
          4. Caicedo-Herrara G, Candelo E, Pinilla J, Vidal A, Cruz S, Pachajoa HM. Novel ATP7A gene mutation in a patient with Menkes disease. Appl Clin Genet. Nov 22, 2018; 11:151-155. https://pubmed.ncbi.nlm.nih.gov/30538525.

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