Child Neurology Net

Menkes Syndrome

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Etiology/ Pathogenesis

A disease of deficient transport of copper in the gastrointestinal tract, results in overall copper deficiency. Manifestations of the syndrome are primarily due to the resulting deficiency of copper dependent enzymes in muscle, brain, and liver. There are also vascular manifestations manifested as intimal disruption, resulting in cleavage.

Age of Onset

<3 mo

Classic Presentation

Present during the neonatal period with seizures, either myoclonic or tonic-clonic in nature, often provoked by stimulation. The infant becomes less active and gradually more lethargic, exhibiting first developmental delay and then regression. Hypothermia and failure to thrive are commonly seen.

Facial abnormalities are often seen, for example full cheeks, high palate, the nasal bridge is depressed, teeth erupt later, and micrognathia is seen. Hair and eyebrows are characteristically sparse, wiry and easily breakable with poor pigmentation.

Connective tissue abnormalities are common, such as umbilical and inguinal hernias, loose skin and joint hypermobility.

Skeletal abnormalities seen include osteoporosis, pectus excavatum and multiple congenital fractures and deformities.

Rarer Symptoms

Usual Course

Progression of neurodegenerative changes over time, usually dead by 12-36 months, survival into teens and 20s has been reported

Genetics

Xq13

Gene encodes a copper transporting ATPase

Chorionic villi can be used for 1st trimester diagnosis

Groups at high risk

Diagnostic Testing

Serum copper <70 mg/dL (reference 80-160)

Serum ceruloplasmin <20 mg/dL (reference 20-60)

Genetic testing- diagnostic, available prenatally

EEG- often reveals hypsarrhythmia and paroxysmal discharges

X-Ray- multiple fractures, similar to osteogenesis imperfecta

Biopsy of the brain- meningoencephalitits, mononuclear and eosinophilic cell infiltration, myelin is affected more severely than the encompassed axons, areas that are myelinated postnatally are almost completely destroyed. Gliosis is prominent
Pronounced loss of the internal granule cell layer and loss and distortion of the purkinje cells in the cerebellum.

CT or MRI- cerebral atrophy and low-density cortical areas, enlarged and tortuous vessels.

Differential

Child abuse
Leigh disease
Phenylketonuria (PKU)
Trichorrhexis nodosa
Biotin deficiency
Argininosuccinic aciduria
Pollitt syndrome
Citrullinemia
Trichothiodystrophy

Treatment

Copper supplementation may prolong survival

Some clinical reports of copper-histidine therapy helping

Misc

Websites with additional info

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Etiology/ Pathogenesis	A disease of deficient transport of copper in the gastrointestinal tract, results in overall copper deficiency. Manifestations of the syndrome are primarily due to the resulting deficiency of copper dependent enzymes in muscle, brain, and liver. There are also vascular manifestations manifested as intimal disruption, resulting in cleavage.
Age of Onset	<3 mo
Classic Presentation	Present during the neonatal period with seizures, either myoclonic or tonic-clonic in nature, often provoked by stimulation. The infant becomes less active and gradually more lethargic, exhibiting first developmental delay and then regression. Hypothermia and failure to thrive are commonly seen. Facial abnormalities are often seen, for example full cheeks, high palate, the nasal bridge is depressed, teeth erupt later, and micrognathia is seen. Hair and eyebrows are characteristically sparse, wiry and easily breakable with poor pigmentation. Connective tissue abnormalities are common, such as umbilical and inguinal hernias, loose skin and joint hypermobility. Skeletal abnormalities seen include osteoporosis, pectus excavatum and multiple congenital fractures and deformities.
Rarer Symptoms
Usual Course	Progression of neurodegenerative changes over time, usually dead by 12-36 months, survival into teens and 20s has been reported
Genetics	Xq13 Gene encodes a copper transporting ATPase Chorionic villi can be used for 1st trimester diagnosis
Groups at high risk
Diagnostic Testing	Serum copper <70 mg/dL (reference 80-160) Serum ceruloplasmin <20 mg/dL (reference 20-60) Genetic testing- diagnostic, available prenatally EEG- often reveals hypsarrhythmia and paroxysmal discharges X-Ray- multiple fractures, similar to osteogenesis imperfecta Biopsy of the brain- meningoencephalitits, mononuclear and eosinophilic cell infiltration, myelin is affected more severely than the encompassed axons, areas that are myelinated postnatally are almost completely destroyed. Gliosis is prominent Pronounced loss of the internal granule cell layer and loss and distortion of the purkinje cells in the cerebellum. CT or MRI- cerebral atrophy and low-density cortical areas, enlarged and tortuous vessels.
Differential	Child abuse Leigh disease Phenylketonuria (PKU) Trichorrhexis nodosa Biotin deficiency Argininosuccinic aciduria Pollitt syndrome Citrullinemia Trichothiodystrophy
Treatment	Copper supplementation may prolong survival Some clinical reports of copper-histidine therapy helping
Misc
Websites with additional info