Cystinuria is an inherited renal and intestinal disease characterized by defective amino acids reabsorption and cystine urolithiasis. It is unusually associated with neurologic symptoms. Mutations in two genes, SLC3A1 and SLC7A9, have been identified in cystinuric patients. This report presents a 13-yr-old boy with cystinuria who manifested difficulty in walking, ataxia, and mental retardation. Somatosensory evoked potential of posterior tibial nerve stimulation showed the central conduction dysfunction through the posterior column of spinal cord. He was diagnosed non-type I cystinuria by urinary amino acid analysis and oral cystine loading test. We screened him and his family for gene mutation by direct sequencing of SLC3A1 and SLC7A9 genes. In this patient, we identified new missence mutation G173R in SLC7A9 gene.
Adolescent ; Amino Acid Substitution ; Amino Acid Transport Systems, Basic/*genetics ; Amino Acids/urine ; Ataxia/complications/diagnosis/*genetics ; Base Sequence ; Cystine/blood ; Cystinuria/complications/diagnosis/*genetics ; Humans ; Intellectual Disability/complications/diagnosis/*genetics ; Male ; *Mutation, Missense ; Pedigree ; Republic of Korea

Albinism, Oculocutaneous ; complications ; diagnosis ; genetics ; Angelman Syndrome ; complications ; diagnosis ; genetics ; Child ; Chromosomes, Human, Pair 15 ; Developmental Disabilities ; etiology ; genetics ; Epilepsy ; etiology ; genetics ; Female ; Humans ; Intellectual Disability ; etiology ; genetics ; Karyotyping

OBJECTIVETo analyze clinical characteristics of a combination of dystrophinopathies and Klinefelter's syndrome (karyotype 47, XXY) in one patient.

METHODThe patient was diagnosed as Duchenne muscular dystrophy (DMD) and Klinefelter's syndrome in Beijing Children's Hospital in March, 2013. The clinical manifestations, physical examinations and laboratory test results were analyzed respectively. The clinical characteristics of four cases reported previously were analyzed as well.

RESULTThe 8.5 years old boy presented with symptoms of walking disorder and developmental delay. The patient had facial dysmorphism, waddling gait, Gower's manoeuvre and enlarged calves.Serum creatine kinase level was 21 040 U/L, and he had mild intellectual impairment. Deletions of exons 49-54 of the dystrophin gene were found.Gene dosage analysis revealed a heterozygous deletion in his mother. Five cases have been reported till now, their age ranged from 3.5 to 18 years; 3 of them were DMD, while the other 2 cases were Becker muscular dystrophy (BMD). One of them, detected in pedigree study, whose weakness was minimal in contrast to the proband. The others came to the hospital because of walking disorder or developmental delay. All the patients had enlarged calves, some of them also had Gower's manoeuvre and waddling gait. The patients' height was between 3 rd and 50 th percentile, while 2 of them had facial dysmorphism.Some degree of mental impairment is usual. Their serum creatine kinase were 2 469-24 750 U/L.One of them was detected in pedigree study. Three of them were diagnosed by muscle biopsy, while in the other one mutation analysis was used.

CONCLUSIONThe combination of dystrophinopathies and Klinefelter's syndrome is quite rare, and has clinical features of these two diseases. Mutation analysis (or muscle biopsy) and karyotype analysis can finally diagnose the syndrome.

Child ; Creatine Kinase ; blood ; DNA Mutational Analysis ; Dystrophin ; genetics ; metabolism ; Exons ; genetics ; Gene Deletion ; Heterozygote ; Humans ; Intellectual Disability ; Klinefelter Syndrome ; complications ; diagnosis ; genetics ; Male ; Muscle Weakness ; etiology ; Muscular Dystrophy, Duchenne ; complications ; diagnosis ; genetics ; Mutation ; Pedigree

A boy was admitted at the age of 17 months. He had psychomotor retardation in early infancy. Physical examination revealed microcephalus, unusual facies, and a single palmar crease on his right hand, as well as muscle hypotonia in the extremities and hyperextension of the bilateral shoulder and hip joints. Genetic detection identified two pathogenic compound heterozygous mutations, c.8868-1G>A (splicing) and c.11624_11625del (p.V3875Afs*10), in the VPS13B gene, and thus the boy was diagnosed with Cohen syndrome. Cohen syndrome is a rare autosomal recessive disorder caused by the VPS13B gene mutations and has complex clinical manifestations. Its clinical features include microcephalus, unusual facies, neutropenia, and joint hyperextension. VPS13B gene detection helps to make a confirmed diagnosis.
Base Sequence ; Developmental Disabilities ; diagnosis ; genetics ; Fingers ; abnormalities ; Humans ; Infant ; Intellectual Disability ; diagnosis ; genetics ; Male ; Microcephaly ; diagnosis ; genetics ; Muscle Hypotonia ; diagnosis ; genetics ; Mutation ; Myopia ; diagnosis ; genetics ; Neutropenia ; complications ; genetics ; psychology ; Obesity ; diagnosis ; genetics ; Psychomotor Disorders ; diagnosis ; etiology ; genetics ; Retinal Degeneration ; diagnosis ; genetics ; Vesicular Transport Proteins ; genetics

Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency.
17-alpha-Hydroxyprogesterone/blood ; 46, XY Disorders of Sex Development/drug therapy/*genetics ; Adolescent ; Adrenal Hyperplasia, Congenital/drug therapy/*genetics ; Adrenal Insufficiency/*congenital/diagnosis/drug therapy/genetics ; Adrenocorticotropic Hormone/*metabolism ; Bone Development/genetics ; Child ; Child, Preschool ; DAX-1 Orphan Nuclear Receptor/genetics ; Female ; Genetic Diseases, X-Linked/drug therapy/*genetics ; Genotype ; Glucocorticoids/therapeutic use ; Humans ; Intellectual Disability/complications ; Male ; Mineralocorticoids/therapeutic use ; Obesity/complications ; Phosphoproteins/genetics ; Puberty, Precocious/complications ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics