OBJECTIVETo study the clinical and laboratory features of the patients with Menkes disease.

METHODThree infants were diagnosed as Menkes disease. Their clinical feature, laboratory findings, radiological manifestation and genes were reviewed.

RESULTAll the three cases were male infants. Their clinical manifestations began at the 3, 5 and 6 months after birth. They all had light complexion, sparse fuzzy woolly hair. The main clinical manifestation was severe mental retardation. The first and the third case also had focal clonus seizures. The second case had feeding difficulty after birth. Their hair showed pili torti and trichorrhexis nodosa microscopically. Their ceruloplasmin in plasma were 32.3 mg/L, 72.5 mg/L and 60.7 mg/L, which were significantly lower as compared with the normal values. Their neuroimaging findings were cortical atrophy, delayed myelination of the white matter and tortuosity of the intracranial vessels. The gene examination of the first and the second case showed deletion and nonsense mutation on exon 14 respectively.

CONCLUSIONMenkes disease is an X-linked recessive disorder characterized by a copper-transporting ATPase defect. The main clinical manifestation is progressive nerve damage. Patients with the disease have special face and hair abnormality, and have morphological changes of brain blood vessels and cerebral atrophy.

Ceruloplasmin ; analysis ; Clinical Laboratory Techniques ; Humans ; Infant ; Male ; Menkes Kinky Hair Syndrome ; blood ; diagnosis

We report here on the diffusion-weighted imaging of unusual white matter lesions in a case of Menkes disease. On the initial MR imaging, the white matter lesions were localized in the deep periventricular white matter in the absence of diffuse cortical atrophy. The lesion showed diffuse high signal on the diffusion-weighted images and diffuse progression and persistent hyperintensity on the follow up imaging. Our case suggests that the white matter lesion may precede diffuse cortical atrophy in a patient with Menkes disease.
Menkes Kinky Hair Syndrome/*diagnosis ; Male ; Infant ; Humans ; *Diffusion Magnetic Resonance Imaging ; Diagnosis, Differential ; Brain Diseases/*diagnosis ; Atrophy

Menkes disease, so called kinky-hair syndrome, is a rare fatal X-linked recessive disorder, which is caused by a mutation in the ATP7A gene encoding the copper transporting ATPase. Dysfunction of copper-dependent enzymes results in various clinical features, including skin and hair hypopigmentation, progressive neurologic degeneration, bone and connective tissue alterations with soft doughy skin and joint laxity, and vascular abnormalities, including aneurysms and bladder diverticula. Patients have the characteristic hair, which is kinky, colorless or steel-colored, and brittle with cutis laxa. Early diagnosis and treatments are perquisites for improving the clinical outcomes. Herein, we describe a rare case of Menkes disease accompanied by hair abnormality and cutis laxa in a 35-days-old boy.
Adenosine Triphosphatases ; Aneurysm ; Connective Tissue ; Copper ; Cutis Laxa ; Diverticulum ; Early Diagnosis ; Hair ; Hair Diseases ; Humans ; Hypopigmentation ; Joint Instability ; Menkes Kinky Hair Syndrome ; Skin ; Urinary Bladder

Menkes disease, so called kinky-hair syndrome, is a rare fatal X-linked recessive disorder, which is caused by a mutation in the ATP7A gene encoding the copper transporting ATPase. Dysfunction of copper-dependent enzymes results in various clinical features, including skin and hair hypopigmentation, progressive neurologic degeneration, bone and connective tissue alterations with soft doughy skin and joint laxity, and vascular abnormalities, including aneurysms and bladder diverticula. Patients have the characteristic hair, which is kinky, colorless or steel-colored, and brittle with cutis laxa. Early diagnosis and treatments are perquisites for improving the clinical outcomes. Herein, we describe a rare case of Menkes disease accompanied by hair abnormality and cutis laxa in a 35-days-old boy.
Adenosine Triphosphatases ; Aneurysm ; Connective Tissue ; Copper ; Cutis Laxa ; Diverticulum ; Early Diagnosis ; Hair ; Hair Diseases ; Humans ; Hypopigmentation ; Joint Instability ; Menkes Kinky Hair Syndrome ; Skin ; Urinary Bladder

More than 6,000 rare disorders including genetic diseases have been reported. Of them, 1,500 diseases (1,211 for clinical diagnosis and 289 for research only) are technically possible for genetic testing. In Korea, since 2005, only 63 genetic diseases is permitted for prenatal genetic testing by the "Bioethics and Biosafety Law". The article 25 in the law prescribes 63 genetic diseases without clear indication for its selection and inclusion criteria. In EU, USA, and other foreign countries, however, there is no provision in the statute on prenatal genetic testing; it is not restricted by a law. Recently, a woman (Mrs. L, 38y) who is a carrier for Menkes disease made an appeal to a government for an amendment of the "Bioethics and Biosafety Law" prohibiting the prenatal diagnosis of her pregnancy at risk for Menkes disease. Menkes disease (MNK) is an X-linked recessive disorder characterized by neurodegeneration, connective tissue defects and hair abnormalities, and no effective treatment is available yet. The prevalence rate of MNK is one in about 250,000 live births. Menkes syndrome patients fail to absorb copper from the gastrointestinal tract in quantities adequate for meeting nutritional needs. These needs seem particularly acute during the initial 12 month of life, when the velocity of brain growth and motor neurodevelopment. Most of pts. die around 3yrs. of age. Mrs. L had a boy with Menkes disease who died at 2y.o. in 2001. Subsequent pregnancy in 2003, she was able to have prenatal genetic testing for mutation of the Menkes (ATP7A) gene and delivered a healthy baby boy. Now, She is pregnant again and wants to have prenatal diagnosis. however, this time, she was not allowed to have any more because Menkes disease is not included in 63 genetic diseases permitted by the law for prenatal genetic testing, in spite of the fact that she is a Menkes disease carrier and her pregnancy is at risk to have an affected baby. This case shows the practical problem of the legal restriction for prenatal genetic testing in Korea. In this study, we report a arguable case and discuss the controversial issues in the legal restriction for prenatal genetic testing in Korea.
Brain ; Connective Tissue ; Copper ; Diagnosis ; Female ; Gastrointestinal Tract ; Genetic Testing* ; Hair ; Humans ; Jurisprudence ; Korea* ; Live Birth ; Male ; Menkes Kinky Hair Syndrome ; Pregnancy ; Prenatal Diagnosis ; Prevalence

Menkes disease is a rare, neurodegenerative, copper metabolism disorder characterized by mutations in ATP7A gene. Clinical symptoms include epilepsy, growth delay, reduced muscle strength, skin hyperextension, hair deformation and urologic abnormalities. However, since these clinical symptoms occur 2–3 months after birth, early diagnosis of Menkes disease is very difficult for clinicians. We report here the case of a patient who initially presented urinary tract infection followed by neurologic symptoms of Menkes disease; he was accurately diagnosed via ATP7A genetic analysis and found to harbor a novel mutation. Although neurological symptoms are the primary diagnostic feature of Menkes disease, clinicians should take into account urinary abnormalities as well, which may be an important clue to the early diagnosis of these patients.
Copper ; Early Diagnosis ; Epilepsy ; Hair ; Humans ; Menkes Kinky Hair Syndrome* ; Metabolism ; Muscle Strength ; Neurologic Manifestations ; Parturition ; Skin ; Urinary Tract Infections ; Vesico-Ureteral Reflux*

Menkes disease is a rare X-linked recessive disorder characterized by multi-systemic disorder of copper deficiency caused by ATP7A gene mutation. In this study, the clinical and laboratory features of three patients with Menkes disease were analyzed. Prenatal diagnosis had been performed for a fetus of a family. Three patients were admitted at the age of 8-9 months due to severe epilepsies and marked delayed psychomotor development. Significantly light complexion, pudgy cheeks and sparse fuzzy wooly hair were observed. On their cranial MR imaging, cortical atrophy, leukoencephalopathy, basal ganglia damage and tormesity of the intracranial vessels were found. Their plasma ceruloplasmin decreased to 70.2, 73.5 and 81 mg/L, significantly lower than normal range (210-530 mg/L). c.3914A>G (p. D1305G) was detected on ATP7A gene of case 1 and 2. A novel mutation, c.3265G>T (p.G1089X) was found in case 3. Both of them were firstly found in Chinese patients of Menkes disease. The mother of case 1 was tested at 20 weeks of pregnancy. Karyotype and ATP7A gene studies of the amniocytes were performed for the prenatal diagnosis of her fetus. Normal male karyotypes without c.3914A>G mutation on ATP7A gene was showed. Postnatal genetic analysis and normal development confirmed the prenatal diagnosis.
Adenosine Triphosphatases ; genetics ; Cation Transport Proteins ; genetics ; Copper-transporting ATPases ; Humans ; Infant ; Male ; Menkes Kinky Hair Syndrome ; diagnosis ; genetics ; Mutation ; Prenatal Diagnosis

Menkes disease is an X-linked recessively inherited neurodegenerative disorder of copper metabolism leading to death in early childhood. This disease is characterized by low serum, liver and brain Cu levels, whereas the Cu content in nearly all other organs is increased. The main clinical features are irregular kinky hair, characteristic face, progresssive degeneration of the central nervous system, bone changes, arterial rupture and thrombosis, and instability of temperature. We have experienced a case of Menkes disease in a eight months old male patient, who manifested by seizure, developmental delay, hypotonia, characteristic hair and face along with low levels of serum copper and ceruloplasmin. We report the characteristic findings of cranial MRI and MR angiography in this Menke's patient. In cranial MRI, he showed progressive brain atrophy with subdural hemorrhage and effusion. MR angiography revealed tortuosity of vessels clearly obviating necessity of more invasive conventional arteriography in diagnosis of this disease. This study suggested that cranial MRI and especially MR angiography might be helpful in making early diagnosis of this disease.
Angiography ; Atrophy ; Brain ; Central Nervous System ; Ceruloplasmin ; Copper ; Diagnosis ; Early Diagnosis ; Hair ; Hematoma, Subdural ; Humans ; Liver ; Magnetic Resonance Imaging ; Male ; Menkes Kinky Hair Syndrome ; Metabolism ; Muscle Hypotonia ; Neurodegenerative Diseases ; Rupture ; Seizures ; Thrombosis

Menkes disease is an infantile-onset X-linked recessive neurodegenerative disorder caused by diverse mutations in a copper-transport gene, ATP7A. Affected patients are characterized by progressive hypotonia, seizures, failure to thrive and death in early childhood. Here, we report a case of Menkes disease presented by intractable seizures and infantile spasms. A 3-month-old male infant had visited our pediatric clinic for lethargy, floppy muscle tone, poor oral intake and partial seizures. His hair was kinky, brown colored and fragile. Partial seizures became more frequent, generalized and intractable to antiseizure medications. An EEG showed frequent posteriorly dominant generalized spikes that were consistent with a generalized seizure. From a genetic analysis, a c.2743C>T (p.Gln915X) mutation was detected and diagnosed as Menkes disease. The mutation is a novel one that has not been previously reported as a cause of Menkes disease.
Adenosine Triphosphatases/*genetics ; Asian Continental Ancestry Group/*genetics ; Cation Transport Proteins/*genetics ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Menkes Kinky Hair Syndrome/*diagnosis/genetics ; Mutation ; Republic of Korea ; Seizures/diagnosis ; Sequence Analysis, DNA ; Spasms, Infantile/diagnosis