Menkes' kinky hair syndrome
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《美国医学杂志》
Institute of Child Health, Kottayam, Kerala, India
This one and a half-year-old boy presented with global developmental delay and myoclonic seizures from 3 months of age. Parents had also noticed hypopigmented brittle hair from birth. He was the only child of non consanguineous parents with history of birth asphyxia and low birth-weight. On examination he was found to be fair complexioned with hypopigmented sparse twisted hair, pleigocephaly, global developmental delay, hypothermia and cortical blindness. The child had callus formation from fracture clavicle sustained earlier. He had no head control with varying tone of all limbs, grade two power and exaggerated reflexes. Laboratory investigations: Serum copper (59 micrograms/dl) and serum ceruloplasmin (10 mg/dl) were low, urine neurometabolic screening was normal and EEG showed hypsarrhythmia. MRI revealed severe cerebral and cerebellar atrophy, hydrocephalus and multiple flow voids in the basal regions due to elongated and tortuous vessels. Hair microscopy showed trichorrhexis nodosa.
This child clearly has Menke syndrome. It is an X- linked disease due to an apparent defect in copper absorption from the gut, possibly, resulting from an inadequate transport mechanism. Deficiency of copper affects the Copper containing enzymes and is characterized by major motor seizures, progressive neurologic deterioration, abnormal hair, hypothermia, deformities of the skeleton, abnormally tortuous arteries and early death.[1]
Clinical manifestations include motor seizures, often myoclonic or generalized tonic clonic, with early onset within the first few months of life, most commonly in the neonatal period. Abnormalities of EEG include hypsarrhythmia and paroxysmal discharges. Hypothermia may be prominent. Hair is coarse ,shortened and light coloured, and hair microscopy shows periodic narrowing (monilethrix), twisting (pili torti) and fragmentation ( trichorrhexis nodosa). Face is rounded with a depressed nasal bridge. Motor development is grossly retarded with poor head control and hypotonia, along with severe intellectual impairment. Blindness has also been seen in some patients.
Serum copper and ceruloplasmin levels are low; radiographic studies of skeletal system demonstrate flaring of the ribs and metaphyseal spurring. Arteriograms demonstrate tortuosity of cerebral vessels; Neuroimaging often demonstrates cerebral atrophy, low density cortical areas, enlarged tortuous vessels and sub- dural collections. Treatment with copper-histidine administered subcutaneously is effective, especially if started in the neonatal period as it prevents neurological deterioration.[2] But prognosis is poor and death occurs by 2-3 years due to other complications.
Prenatal diagnosis is possible by chorion villus biopsy and estimation of copper content using radioactive copper uptake in fibroblasts. Molecular methods are also available
References
1. Kenneth F S and Paul RD. Degenerative diseases primarily of grey matter. Pediatric Neurology : Principles and Practice, Vol II , 3rd edn. Mosby 1999 : 833-835.
2. Michael VJ. Neurodegenerative disorders of childhood. In Behrman et al, ed. Nelson Textbook of Pediatrics. 17th edn. Saunders 2004 : 2034.(George Sunil, Matthai Son)
This one and a half-year-old boy presented with global developmental delay and myoclonic seizures from 3 months of age. Parents had also noticed hypopigmented brittle hair from birth. He was the only child of non consanguineous parents with history of birth asphyxia and low birth-weight. On examination he was found to be fair complexioned with hypopigmented sparse twisted hair, pleigocephaly, global developmental delay, hypothermia and cortical blindness. The child had callus formation from fracture clavicle sustained earlier. He had no head control with varying tone of all limbs, grade two power and exaggerated reflexes. Laboratory investigations: Serum copper (59 micrograms/dl) and serum ceruloplasmin (10 mg/dl) were low, urine neurometabolic screening was normal and EEG showed hypsarrhythmia. MRI revealed severe cerebral and cerebellar atrophy, hydrocephalus and multiple flow voids in the basal regions due to elongated and tortuous vessels. Hair microscopy showed trichorrhexis nodosa.
This child clearly has Menke syndrome. It is an X- linked disease due to an apparent defect in copper absorption from the gut, possibly, resulting from an inadequate transport mechanism. Deficiency of copper affects the Copper containing enzymes and is characterized by major motor seizures, progressive neurologic deterioration, abnormal hair, hypothermia, deformities of the skeleton, abnormally tortuous arteries and early death.[1]
Clinical manifestations include motor seizures, often myoclonic or generalized tonic clonic, with early onset within the first few months of life, most commonly in the neonatal period. Abnormalities of EEG include hypsarrhythmia and paroxysmal discharges. Hypothermia may be prominent. Hair is coarse ,shortened and light coloured, and hair microscopy shows periodic narrowing (monilethrix), twisting (pili torti) and fragmentation ( trichorrhexis nodosa). Face is rounded with a depressed nasal bridge. Motor development is grossly retarded with poor head control and hypotonia, along with severe intellectual impairment. Blindness has also been seen in some patients.
Serum copper and ceruloplasmin levels are low; radiographic studies of skeletal system demonstrate flaring of the ribs and metaphyseal spurring. Arteriograms demonstrate tortuosity of cerebral vessels; Neuroimaging often demonstrates cerebral atrophy, low density cortical areas, enlarged tortuous vessels and sub- dural collections. Treatment with copper-histidine administered subcutaneously is effective, especially if started in the neonatal period as it prevents neurological deterioration.[2] But prognosis is poor and death occurs by 2-3 years due to other complications.
Prenatal diagnosis is possible by chorion villus biopsy and estimation of copper content using radioactive copper uptake in fibroblasts. Molecular methods are also available
References
1. Kenneth F S and Paul RD. Degenerative diseases primarily of grey matter. Pediatric Neurology : Principles and Practice, Vol II , 3rd edn. Mosby 1999 : 833-835.
2. Michael VJ. Neurodegenerative disorders of childhood. In Behrman et al, ed. Nelson Textbook of Pediatrics. 17th edn. Saunders 2004 : 2034.(George Sunil, Matthai Son)