A 7-year-old girl was admitted to the hospital with rapidly progressive vision loss. Since 1 year of age, she had exhibited developmental delay accompanied by visual impairment and neutropenia. Combined with genetic testing and molecular pathogenicity analysis, she was diagnosed with Cohen syndrome (CS) caused by compound heterozygous variants in VPS13B (c.6940+1G>T and c.2911C>T). The c.6940+1G>T variant resulted in exon 38 skipping, leading to a frameshift and premature termination. Reverse transcription quantitative polymerase chain reaction revealed significantly reduced VPS13B gene expression (P<0.05). Bioinformatic analysis suggested that both variants likely produce truncated proteins. This case highlights that integrating clinical features with molecular pathogenicity assessment (DNA, RNA, and protein analysis) can improve early diagnostic accuracy for CS.
Humans ; Female ; Child ; Vesicular Transport Proteins/genetics* ; Developmental Disabilities/etiology* ; Muscle Hypotonia/etiology* ; Myopia/etiology* ; Heterozygote ; Intellectual Disability/etiology* ; Microcephaly/etiology* ; Obesity/genetics* ; Growth Disorders/etiology* ; Retinal Degeneration/genetics* ; Psychomotor Disorders/genetics* ; Fingers/abnormalities*

A girl, aged 22 months, attended the hospital due to recurrent vulvar rashes for more than half a year. Skin biopsy showed Langerhans cell histiocytosis, and evaluation of systemic conditions showed no systemic involvement. Therefore, the girl was diagnosed with Langerhans cell histiocytosis (skin type). In conclusion, for rashes on the vulva alone, if there are no specific clinical manifestations, the possibility of Langerhans cell histiocytosis should be considered after molluscum contagiosum, sexually transmitted diseases, and Fordyce disease are excluded.
Developmental Disabilities ; Exanthema/etiology* ; Female ; Histiocytosis, Langerhans-Cell ; Humans ; Infant ; Vulvar Diseases/diagnosis*

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

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive hereditary disease and is a congenital metabolic disorder of neurotransmitter biosynthesis. It is mainly manifested as hypotonia, oculogyric crisis, autonomic dysfunction, and developmental delay. This article reports a boy manifested as delayed motor development, hypotonia, and oculogyric crisis. Gene screening for metabolic disorders revealed new compound heterozygous mutations, c.1063dupA (p.I355fs) and c.250A>C (p.S84R), in the exon of DDC gene. The boy had a significant increase in 3-O-methyldopa as measured by dried blood spot. Therefore, he was diagnosed with AADC deficiency. After treatment with the dopamine receptor agonist pramipexole dihydrochloride, the catechol-O-methyltransferase inhibitor entacapone, and vitamin B6, the boy showed mild improvements in hypotonia, blepharoptosis, and oculogyric crisis. Clinical physicians should enhance their ability for identifying AADC deficiency, so as to facilitate early diagnosis and treatment of this disorder. Genetic counseling for birth health and prenatal diagnosis should be performed for parents in need.
Amino Acid Metabolism, Inborn Errors ; complications ; Aromatic-L-Amino-Acid Decarboxylases ; deficiency ; Developmental Disabilities ; etiology ; Feeding and Eating Disorders ; etiology ; Humans ; Infant ; Male ; Nystagmus, Pathologic ; etiology

OBJECTIVETo investigate the influence of family environment on developmental coordination disorder (DCD) in preschool children.

METHODSStratified random cluster sampling was used to select 1 727 children (4-6 years old). The Movement Assessment Battery for Children was used to screen out the children with DCD. The Family Environment Scale on Motor Development for Preschool Urban Children and a self-designed questionnaire were used to assess family environment.

RESULTSA total of 117 children were confirmed with DCD. There were significant differences in mother's education level and family structure between the DCD and normal control groups. There were also significant differences in the scores of "Let children manage their daily items" and "Arrange all affairs" between the DCD and normal control groups. The multivariate logistic regression analysis indicated that when children's age and gender were controlled, mother's education level, family structure, "Let children manage their daily items", and "Arrange all affairs" were main factors influencing the development of DCD in children (P<0.05).

CONCLUSIONSFamily environment may affect the development of DCD in preschool children. Therefore, parents should not arrange all affairs for children and should provide more opportunities for children to manage their daily life, in order to promote the development of early motor coordination and prevent the development of DCD.

Child ; Child, Preschool ; Developmental Disabilities ; etiology ; Environment ; Family ; Female ; Humans ; Logistic Models ; Male

OBJECTIVETo examine the association between autism spectrum disorder (ASD) and epilepsy in children.

METHODSA total of 190 children with ASD were enrolled. A self-designed questionnaire, Childhood Autism Rating Scale, and Autism Behavior Checklist were used to determine the association between ASD and epilepsy.

RESULTSAmong the 190 children with ASD, 20 (10.5%) had epileptic seizures and 12 (6.3%) were diagnosed with epilepsy. The rates of abnormal physical development and hearing disorders before the age of one year were significantly higher in ASD children with epileptic seizures than in those without epileptic seizures (P<0.05). The ASD children diagnosed with epilepsy and those receiving epilepsy treatment had a significantly increased rate of abnormal physical development before the age of one year (P<0.05). The ASD children with epileptic seizures had poorer sensory responses and behavioral competencies than those without epileptic seizures (P<0.05). Epilepsy treatment have a positive effect on behavioral competencies in ASD children (P<0.05).

CONCLUSIONSThere is a significant association between ASD and epilepsy in children. The possibility of the comorbidity between ASD and epilepsy may be assessed according to the status of growth and development before the age of one year, sensory responses and behavioral competencies, and the presence or absence of epileptic seizures.

Adolescent ; Autism Spectrum Disorder ; complications ; Child ; Child, Preschool ; Developmental Disabilities ; etiology ; Epilepsy ; complications ; Female ; Hearing Disorders ; etiology ; Humans ; Male

OBJECTIVETo explore the value of urine gas chromatography-mass spectrometry (GC-MS) in the screening of children at risk of inherited metabolic diseases (IMD), and to identify the disease spectrum of IMD and the clinical characteristics of children with IMD.

METHODSThe clinical data of 15 851 children at risk of IMD who underwent urine GC-MS in the Tianjin Children's Hospital between February 2012 and December 2016 were retrospectively analyzed.

RESULTSIn the 15 851 children, 5 793 (36.55%) were detected to have metabolic disorders. A total of 117 (0.74%) children were confirmed to have IMD, including 77 cases of methylmalonic acidemia (65.8%). The clinical manifestations of confirmed cases in the neonatal period mainly included jaundice, metabolic acidosis, abnormal muscular tension, feeding difficulty, poor response, and lethargy or coma. The clinical manifestations of confirmed cases in the non-neonatal period mainly included delayed mental and motor development, metabolic acidosis, convulsion, recurrent vomiting, and anemia.

CONCLUSIONSGC-MS is an effective method for the screening for IMD in children at risk. Methylmalonic acidemia is the most common IMD. The clinical manifestations of IMD are different between the confirmed cases in the neonatal and non-neonatal periods.

Acidosis ; etiology ; Adolescent ; Amino Acid Metabolism, Inborn Errors ; complications ; diagnosis ; Child ; Child, Preschool ; Developmental Disabilities ; etiology ; Female ; Gas Chromatography-Mass Spectrometry ; Humans ; Infant ; Infant, Newborn ; Male ; Metabolism, Inborn Errors ; complications ; diagnosis ; Retrospective Studies ; Risk

OBJECTIVETo investigate the neurodevelopmental outcomes of extremely low birth weight (ELBW) and very low birth weight (VLBW) infants at a corrected age (CA) of 18 months and related factors influencing the outcomes.

METHODSThe ELBW and VLBW infants who were admitted to the neonatal intensive care unit, survived, and discharged between January 2013 June 2014 were enrolled. These infants were followed up at CAs of 40 weeks and 1, 3, 6, 12, and 18 months to evaluate the neurodevelopmental outcomes. According to the neurodevelopmental status, the infants were divided into normal and abnormal neurodevelopment groups. The differences in clinical data were compared, and the risk factors for abnormal neurodevelopment in ELBW and VLBW infants were analyzed.

RESULTSA total of 338 ELBW and VLBW infants were enrolled, and 15 died during hospitalization. At the CA of 18 months, 145 infants (44.9%) survived and had complete follow-up data, 75 (23.2%) died, and 103 (31.9%) were lost to follow-up. Of the 145 infants who survived and had complete follow-up data, 71 (49.0%) had neurodevelopmental impairment (NDI), and 3 (2.1%) had cerebral palsy. No infants experienced visual damage with blindness in one or both eyes or hearing loss with a need for hearing aid. The logistic regression analysis showed that bronchopulmonary dysplasia (BDP) (OR=3.530, P<0.001) and sepsis (OR=2.528, P=0.035) were independent risk factors for NDI in ELBW and VLBW infants, and the incidence of NDI increased with the severity of BDP.

CONCLUSIONSSepsis and BPD, especially severe BPD, are risk factors for NDI in ELBW and VLBW infants.

Brain ; growth & development ; Child Development ; Developmental Disabilities ; etiology ; Female ; Humans ; Infant, Extremely Low Birth Weight ; growth & development ; Infant, Low Birth Weight ; growth & development ; Infant, Newborn ; Male

A one-year-old girl visited the hospital due to limb torsion and developmental regression for one month after hand, foot and mouth disease. At the age of 11 months, she visited a local hospital due to fever for 5 days and skin rash with frequent convulsions for 2 days and was diagnosed with severe hand, foot and mouth disease, viral encephalitis, and status epilepticus. Brain MRI revealed symmetric abnormal signals in the bilateral basal ganglia, bilateral thalamus, cerebral peduncle, bilateral cortex, and hippocampus. She was given immunoglobulin, antiviral drugs, and anticonvulsant drugs for 2 weeks, and the effect was poor. Blood and urine screening for inherited metabolic diseases were performed to clarify the etiology. The analysis of urine organic acids showed significant increases in glutaric acid and 3-hydroxyglutaric acid, which suggested glutaric aciduria type 1, but her blood glutarylcarnitine was normal, and free carnitine significantly decreased. After the treatment with low-lysine diets, L-carnitine, and baclofen for 1 month, the patient showed a significant improvement in symptoms. Hand, foot and mouth disease is a common viral infectious disease in children, and children with underlying diseases such as inherited metabolic diseases and immunodeficiency may experience serious complications. For children with hand, foot and mouth disease and unexplained encephalopathy, inherited metabolic diseases should be considered.
Amino Acid Metabolism, Inborn Errors ; etiology ; Brain Diseases, Metabolic ; etiology ; Developmental Disabilities ; etiology ; Female ; Glutaryl-CoA Dehydrogenase ; deficiency ; Hand, Foot and Mouth Disease ; complications ; Humans ; Infant ; Torsion Abnormality ; etiology

OBJECTIVETo investigate the environmental risk factors for autism spectrum disorders (ASD) in children.

METHODSIn this case-control study, 81 boys with ASD, 74 boys with global developmental delay (GDD), and 163 healthy boys were enrolled. A self-designed nurturing environment questionnaire was used to record general demographic data, family social-economic status, parents' living habits and environmental exposure, maternal health status during pregnancy, birth situations, and rearing environment after birth. Multivariate logistic regression was used to identify environmental risk factors for ASD and GDD.

RESULTSMultivariate logistic regression analysis showed that six environmental risk factors such as maternal occupational toxicant exposure, diseases during pregnancy and a history of passive smoking, children's birth places, the frequency of outdoor activities in the second year after birth, and the opportunities to communicate with other age-matched children were significantly associated with the incidence of ASD (OR=20.67, 3.559, 2.422, 2.646, 23.820, and 5.081, respectively; P<0.05). Among the above six risk factors, passive smoking during pregnancy, the opportunities to communicate with their peers, and the frequency of outdoor activities in the second year after birth were also significantly associated with the incidence of GDD (P<0.05).

CONCLUSIONSMaternal occupational toxicant exposure, diseases during pregnancy, and low level of children's birth places may be the specific risk factors associated with ASD, and passive smoking during pregnancy, fewer opportunities to communicate with their peers, and fewer outdoor activities in the second year after birth are non-specific risk factors for ASD, indicating that the development of ASD may be influenced by both genes and environmental factors.

Autism Spectrum Disorder ; etiology ; Case-Control Studies ; Child, Preschool ; Developmental Disabilities ; etiology ; Female ; Humans ; Logistic Models ; Male ; Maternal Exposure ; Pregnancy ; Risk Factors ; Tobacco Smoke Pollution ; adverse effects