Subject(s)
Abnormalities, Multiple/diagnosis , Craniofacial Abnormalities/diagnosis , Intellectual Disability/diagnosis , Limb Deformities, Congenital/diagnosis , Craniofacial Abnormalities/complications , Humans , Infant , Intellectual Disability/complications , Limb Deformities, Congenital/complications , MaleABSTRACT
We report a case with a new syndrome that presents with glaucoma, cryptorchidism, oculocutaneous albinism, ataxia, hypotonia, autistic behaviour besides various major and minor craniofacial dysmorphic, skeletal, and neuroimaging findings, and suggest that this case represents a new syndrome not reported previously.
Subject(s)
Albinism, Oculocutaneous/genetics , Craniofacial Abnormalities/genetics , Cryptorchidism/genetics , Glaucoma/genetics , Intellectual Disability/genetics , Albinism, Oculocutaneous/diagnosis , Ataxia/diagnosis , Ataxia/genetics , Brain/abnormalities , Brain/pathology , Child Development Disorders, Pervasive/diagnosis , Child Development Disorders, Pervasive/genetics , Child, Preschool , Choristoma/diagnosis , Craniofacial Abnormalities/diagnosis , Cryptorchidism/diagnosis , Glaucoma/diagnosis , Humans , Intellectual Disability/diagnosis , Magnetic Resonance Imaging , Male , SyndromeABSTRACT
A 25-year-old female was referred for short stature and joint deformities. Except for previous corneal transplantation, her medical history was unremarkable. Initial physical examination revealed the presence of a coarse facies, short neck, kyphosis, restricted joint movements and deformities, and cardiac murmur besides a normal intellect. Urine glycosaminoglycan levels were high, and blood enzyme assay indicated significantly low alpha-L-iduronidase levels. Mucopolysaccharidosis I (MPS I) was diagnosed and prompted the onset of enzyme replacement therapy (ERT), which significantly improved articular complaints, while cardiac pathology remained stable. At the eighteenth month of ERT, sudden vision loss developed. She spontaneously recovered her vision in a month. MPS I is a progressive disease, in which tissue accummulation of heparan and dermatan sulphate result from defective activity or lack of alpha-L-iduronidase. ERT in MPS I usually presents favourable outcomes or at least stabilization of symptoms. This present case qualifies as the first report ofa MPS I patient developing sudden vision loss under ERT. We suggest that further research studies are warranted for defining the efficiency and possible limitations of ERT.
Subject(s)
Blindness/chemically induced , Blindness/diagnosis , Enzyme Replacement Therapy/methods , Iduronidase/adverse effects , Iduronidase/therapeutic use , Mucopolysaccharidosis I/diagnosis , Mucopolysaccharidosis I/drug therapy , Adult , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Infusions, Intravenous , Remission, SpontaneousABSTRACT
The efficacy and utility of the Connexin-26 (Cx-26) gene (also called GJB2) analysis from DNA isolated from Guthrie newborn screening cards is demonstrated. This analysis precisely defined a major cause of prelingual nonsyndromic deafness in those children requiring amplification in our study. Guthrie cards were obtained from 49 deaf children requiring amplification identified over the last 5 years by the Rhode Island Newborn Screening Program. Children with syndromes or other recognizable causes of hearing loss were excluded. DNA was extracted from the Guthrie cards and analyzed sequentially for the Cx-26 35delG mutation and then for the 167delT mutation followed by gene sequencing on remaining heterozygotes. Three of 42 children were 35delG homozygotes; 2/42 children were 35delG/167delT compound heterozygotes. One child was identified as being a 35delG heterozygote with no other mutation found by sequencing. Nine Guthrie cards yielded no amplification or uninterpretable results. Cx-26 mutations were identified as causing 11.9% of the deafness in the children studied. In conclusion, Cx-26 analysis is an important test that identifies a major cause of prelingual nonsyndromic deafness. Molecular analysis of hearing-impaired newborns will be important for genetic counseling in these families. Failures with Guthrie cards may make use of other collection methods preferable.
