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Menkes Disease
MK
Presentation
- There are no published reports of congenital skull fracture as a presenting sign of Menkes disease.[ncbi.nlm.nih.gov]
- METHODS: We present in vitro modeling for impaired osteogenesis in MD using human induced pluripotent stem cells (iPSCs) with a mutated ATP7A gene. MD-iPSC lines were generated from two patients harboring different mutations.[ncbi.nlm.nih.gov]
- Others, such as seizures, cerebral atrophy, and cerebrovascular tortuosity may be present but are under-reported and under- studied.[ncbi.nlm.nih.gov]
- The patient presented with a mild tremor at 2 days after delivery. A brain computed tomography (CT) scan showed an acute EDH in the posterior fossa, extending into the occipitoparietal area.[ncbi.nlm.nih.gov]
- RESULTS: The Menkes mRNA and protein were present in the RPE and neurosensory retina whereas the Wilson mRNA and protein were limited to the RPE. In the RPE, both proteins localized to the Golgi.[ncbi.nlm.nih.gov]
Immune System
Massive Splenomegaly
- In addition, 1 boy developed a previously unreported anomaly, namely, massive splenomegaly and hypersplenism as a consequence of a splenic artery aneurysm.[ncbi.nlm.nih.gov]
Entire Body System
Hypothermia
- Cardinal features include hair abnormalities, facial dysmorphism, severe neurological impairment, hypothermia, arterial anomalies, bone abnormalities and a fatal outcome.[ncbi.nlm.nih.gov]
- Menkes syndrome should be considered in any male infant with unexplained seizures, hypothermia, and mental retardation.[accessanesthesiology.mhmedical.com]
- In the early neonatal period, patients may present with prolonged jaundice, hypothermia, hypoglycemia and feeding difficulties. Pectus excavatum and umbilical and inguinal hernias have also been reported.[orpha.net]
- Patients with Menkes disease may also present hair changes (short, sparse, coarse, twisted hair, and colorless or steel-colored), hypothermia, hypoglycemia, hypotonia, and seizures. Onset of Menkes disease typically begins in the neonatal period.[asperbio.com]
Epilepsy
- BACKGROUND: Epilepsy is a frequent and severe feature of Menkes disease (MD) but only few studies described the long-term evolution of these children.[ncbi.nlm.nih.gov]
- Epilepsy is a major clinical feature of this disorder. We describe the clinical presentation, evolution of epilepsy and explore the biological underpinnings of epileptogenesis in Menkes disease.[ncbi.nlm.nih.gov]
- There are few reports of epilepsy and electroencephalography (EEG) findings and few reports of MD patients in Korea. We explored MD genotypes and phenotypes, including epilepsy, in Korean patients.[ncbi.nlm.nih.gov]
- , syndromic hair shaft abnormality, eyebrow/eyelashes structural anomaly, epidermal disease, metal transport or utilization disorder with epilepsy Normdatei Q639203 Reasonator Scholia Statistik[commons.wikimedia.org]
- , syndromic hair shaft abnormality, eyebrow/eyelashes structural anomaly, epidermal disease, metal transport or utilization disorder with epilepsy Controllo di autorità Q639203 Reasonator Scholia Statistica[commons.wikimedia.org]
Short Stature
- stature, and intellectual disabilities) 759.89 Rud's (mental deficiency, epilepsy, and infantilism) 759.89 Russell (-Silver) (congenital hemihypertrophy and short stature) 759.89 Seckel's 759.89 sick Silver's (congenital hemihypertrophy and short stature[icd9data.com]
Soft Tissue Mass
- He developed respiratory problems requiring continuous supplemental oxygen and a progressively enlarging soft tissue mass appeared on the neck. Imaging studies revealed cystic spaces in multiple lobes of the lung consistent with bullous emphysema.[ncbi.nlm.nih.gov]
Gastrointestinal
Failure to Thrive
- 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.[ncbi.nlm.nih.gov]
- Deficiency in copper-dependent enzymes results in the unique kinky hair appearance, neurodegeneration, developmental delay, seizures, failure to thrive and other connective tissue or organ abnormalities.[ncbi.nlm.nih.gov]
- Patients with MD are characterized by progressive hypotonia, seizures, failure to thrive, and death in early childhood. Two Korean patients were diagnosed with Menkes disease by clinical and biochemical findings.[ncbi.nlm.nih.gov]
- We describe a child with classical Menkes disease with a novel ATP7A mutation, intractable seizures, severe hypotonia and developmental delay, hypopigmentation of the skin and hair, and failure to thrive, who was treated with daily subcutaneous copper[ncbi.nlm.nih.gov]
- Untreated affected individuals suffer failure to thrive and neurodevelopmental delays that usually commence at 6-8 weeks of age. Death by age three years is typical.[ncbi.nlm.nih.gov]
Epigastric Mass
- A 4-year-old Taiwanese male patient with MD was referred to the hospital and presented with a palpable epigastric mass. On the basis of the findings of ultrasonography and enhanced computed tomography, the diagnosis was retroperitoneal hematoma.[ncbi.nlm.nih.gov]
Skin
Alopecia
- Required Differential Diagnosis & Pitfalls Other disorders associated with pili torti : Bjornstad syndrome Crandall syndrome Mitochondrial disorders Netherton syndrome Bazex-Dupré-Christol syndrome Citrullinemia Laron syndrome Child abuse (eg, traumatic alopecia[visualdx.com]
- Diagnosis of Menkes disease was rapidly considered because the child had white fine brittle hair, a partial alopecia, an hypopigmentation and a skin xerosis, an hypothermia and several neurological abnormalities: slow psychomotor development, generalized[esciencecentral.org]
- […] glomerulonephritis, type 3 Holoacardius Holoacardius acephalus Holoacardius acormus Holoacardius amorphus Holt-Oram syndrome Homologous chimera Hyperhidrosis, premature cavities and premolar aplasia Hyperthermia-induced defect Hypogonadism, diabetes mellitus, alopecia[icd9data.com]
Normal Hair
- The microscopic aspect of the patient's hair showing normal hair, silver colored hair, hair shafts twisting 1800, trichoclasis, and trichoptilosis, was highly characteristic for Menkes disease.[ncbi.nlm.nih.gov]
Psychiatrical
Psychomotor Retardation
- Kinky-hair syndrome, a progressive neurodegenerative disorder which affects infant males and is characterized by unusual hair, seizures, psychomotor retardation, growth failure, and early death, was first described by Menkes et al. 1 Since the original[jamanetwork.com]
- Patients are normal in the first 2 or 3 months of life but then they develop failure to thrive, hypothermia, hypotonia, seizures, severe psychomotor retardation, and usually die before 2 years of age.[neuropathology-web.org]
- At the time of examination, he presented psychomotor retardation, hair changes (scarce, thin, coarse), severe head lag and inability to sit independently.[bmcpediatr.biomedcentral.com]
Face, Head & Neck
Pudgy Cheeks
- An odd appearance, with pale skin, frontal or occipital bossing, micrognathia and pudgy cheeks may be observed. Patients develop gradual motor dysfunction and seizures.[orpha.net]
- Typical facies consist of frontal or occipital bossing, abnormal or absent eyebrows, pudgy cheeks with sagging jowls, micrognathia, and pallor.[accessanesthesiology.mhmedical.com]
Neck Mass
- Pediatric neck masses should trigger a high index of suspicion for certain genetic disorders of connective tissue.[ncbi.nlm.nih.gov]
- The neck mass was determined to be an internal jugular venous aneurysm. At autopsy, extensive emphysematous change was evident.[ncbi.nlm.nih.gov]
Neurologic
Seizure
- At the onset, the most frequent type of seizures are FC and IS; in the next months, other kinds of seizures can appear. Many children are drug resistant.[ncbi.nlm.nih.gov]
- 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.[ncbi.nlm.nih.gov]
- Three prior surveys indicated clinical seizures and electroencephalographic (EEG) abnormalities in a combined 27 of 29 (93%) symptomatic Menkes disease patients diagnosed at 2 months of age or older.[ncbi.nlm.nih.gov]
- All but one patient had refractory seizures. Seizure types included multifocal clonic seizures (n 3), myoclonic jerks (n 4) and tonic spasms (n 1). EEG was markedly abnormal in all except in the patient without clinical seizures.[ncbi.nlm.nih.gov]
- The five male patients with identified molecular defects experienced anticonvulsant-resistant seizures. EEGs in focal seizures usually revealed interictal focal epileptiform discharges over the posterior region without focal slowing.[ncbi.nlm.nih.gov]
Focal Seizure
- EEGs in focal seizures usually revealed interictal focal epileptiform discharges over the posterior region without focal slowing.[ncbi.nlm.nih.gov]
- RESULTS: The large majority of our patients presented at the onset of epilepsy focal seizures (FS) and infantile spasms (IS). Five patients had recurrent status epilepticus (SE).[ncbi.nlm.nih.gov]
- Early presentations typically involve focal seizures, with progression to epileptic spasms and a chronic late stage of epilepsy characterized by tonic seizures, myoclonic jerks, and multifocal epileptiform activity on the EEG.[ncbi.nlm.nih.gov]
Progressive Macrocephaly
- We present a case of Menkes disease complicated by progressive macrocephaly following the development of massive subdural haematomas.[ncbi.nlm.nih.gov]
Workup
- Physicians should use microscopic evaluation of the hair more often when suspicion of Menkes disease is raised, aiming a narrow further diagnostic workup and early positive diagnosis and genetic advice for the affected families.[ncbi.nlm.nih.gov]
- (See Etiology, Presentation, and Workup .) Although it is extremely rare in clinical practice, Wilson disease is important because it is often fatal if not recognized and treated when symptomatic.[emedicine.medscape.com]
EEG
Hypsarrhythmia
- The younger boy, followed from birth, started seizures at the age of 3 months and had a hypsarrhythmia-like EEG.[ncbi.nlm.nih.gov]
- This was followed by modified hypsarrhythmia with less polymorphic background activity in spasms and anteriorly dominant diffuse slowing with generalized and multifocal epileptiform discharges in myoclonic or generalized tonic seizures.[ncbi.nlm.nih.gov]
- Electroencephalography (EEG) revealed left hemisphere dominant hypsarrhythmia and slowing in the left hemisphere.[ncbi.nlm.nih.gov]
- While focal epileptiform discharges predominated before six months of age modified hypsarrhythmia was characteristically noted thereafter.[ncbi.nlm.nih.gov]
Focal Epileptiform Discharges
- EEGs in focal seizures usually revealed interictal focal epileptiform discharges over the posterior region without focal slowing.[ncbi.nlm.nih.gov]
- While focal epileptiform discharges predominated before six months of age modified hypsarrhythmia was characteristically noted thereafter.[ncbi.nlm.nih.gov]
Generalized Polyspikes
- EEG showed gross generalized polyspike waves. Opthalmoscopic examination showed pale optic disc. Microscopic examination of hair revealed classical sign of pili torti (Figure 4 ).[casesjournal.biomedcentral.com]
Multifocal Epileptiform Discharges
- This was followed by modified hypsarrhythmia with less polymorphic background activity in spasms and anteriorly dominant diffuse slowing with generalized and multifocal epileptiform discharges in myoclonic or generalized tonic seizures.[ncbi.nlm.nih.gov]
Treatment
- […] duration of treatment.[ncbi.nlm.nih.gov]
- No adverse effects of pamidronate treatment were noted. Pamidronate treatment was associated with an increase in bone mineral density and may be an effective treatment modality for the management of osteoporosis in children with Menkes disease.[ncbi.nlm.nih.gov]
- The description of this new mutation and the response of the patient to Cu-His treatment will contribute to the growing body of knowledge about treatment response in Menkes disease.[ncbi.nlm.nih.gov]
- He was born healthy, biochemical markers were reduced and treatment was indicated. Molecular analysis was performed confirming mutation in both the mother and the proband, while the other son did not have mutation, so treatment was discontinued.[ncbi.nlm.nih.gov]
- During treatment, the lactate signal faded away, whereas the NAA signal gradually increased to a z-score of -1.5 at 120 days of treatment.[ncbi.nlm.nih.gov]
Prognosis
- The prognosis in Menkes disease is dependent on early copper-histidine therapy. Effective treatment has led to children surviving into adulthood. Diagnosing the syndrome during the neonatal period is difficult.[ncbi.nlm.nih.gov]
- Prognosis Prognosis is poor and patients usually die in early childhood. However, careful medical care, and possibly copper administration, may extend life span. The documents contained in this web site are presented for information purposes only.[orpha.net]
- Because of the severity of the prognosis and in order to plan treatment, the correct diagnosis has to be reached quickly. Typical manifestations of the syndrome are likely to develop after 3 months of age, with a pleiotropic appearance.[ncbi.nlm.nih.gov]
- The prognosis in Menkes disease is associated with early detection, early initiation of treatment and with the preservation of some ATP7A activity, which is necessary for Cu-His treatment response.[ncbi.nlm.nih.gov]
- With the advent of subcutaneous copper-histidine therapy, the early diagnosis of Menkes disease becomes of utmost importance for patients' prognosis.[ncbi.nlm.nih.gov]
Etiology
- ., iron and copper) have been implicated in the etiology of many oxidative stress-related diseases including also neurodegenerative disorders.[ncbi.nlm.nih.gov]
- Etiology MD is caused by mutations in the ATP7A gene (Xq21.1) encoding a copper-transport protein, Cu2 -transporting ATPase-alpha polypeptide. To date, about 200 different mutations in this gene have been reported.[orpha.net]
Epidemiology
- Summary Epidemiology Prevalence data are not available. The birth incidence is 1/300,000 in Europe and 1/360,000 in Japan. In Australia, the birth incidence is reported to be much higher (1/50,000-100,000), which may be due to a founder effect.[orpha.net]
Sex distribution
Age distribution
Pathophysiology
- Menkes disease is due to a dysfunction of ATP7A, but the pathophysiology of neurologic manifestation is poorly understood during embryonic development.[ncbi.nlm.nih.gov]
- We hypothesized that gene expression changes in a MD patient with a lethal ATP7A mutation would indicate pathophysiological cascades relevant to the effects of copper deficiency in the developing brain.[ncbi.nlm.nih.gov]
- These contrary results for the thickness of the IEL in the MA and the EA in this animal model of Menkes' disease may reflect differences in the anatomical and pathophysiological properties of the two types of vessels.[ncbi.nlm.nih.gov]
- Pathophysiology Copper is a trace metal in many essential enzyme systems, including cytochrome C oxidase, superoxide dismutase, lysyl oxidase, tyrosinase, ascorbic acid oxidase, ceruloplasmin, and dopamine beta hydroxylase.[emedicine.com]
Prevention
- In MD patients, an early copper-histidine treatment may prevent the neurological impairment and prolong survival leading to an OHS phenotype.[ncbi.nlm.nih.gov]
- Prevention There is no known way to prevent Menkes syndrome. If you have a family history of the disorder, you can talk to a genetic counselor when deciding whether to have children.[winchesterhospital.org]
- Early parenteral administration of copper can prevent the neurological disturbances and lead to a better outcome. In the present study, a survey on MNK in Japan was performed.[doi.org]