Autoimmune thyroiditis in 18q deletion syndrome

Deletion of a segment of the long arm of chromosome 18 causes characteristic physical features and mental retardation. Autoimmune disorders have been described with this syndrome in a limited number of reports. We describe 2 cases of autoimmune hypothyroidism in children with 18q deletion syndrome.     

Measurement of reverse triiodothyronine for the newborn screening of thyroid disorders

Neonates were tested for filter paper blood spot reverse T₃ (rT₃) and Thyroxine (T₄). A significant correlation was found between T₄ and rT₃ levels, however, there was no correlation between low rT₄ and corresponding rT₃ levels. The study shows rT₃ measurement is not more sensitive than T₄ for screening neonates for thyroid disorders and measurement of both T₄ and rT₃ levels does not help in screening out false low T₄ values commonly observed in screening programs.     

A novel mutation in the monocarboxylate transporter 8 gene in a boy with putamen lesions and low free T4 levels in cerebrospinal fluid

We describe brain lesions in a patient with a monocarboxylate transporter 8 mutation. Imaging showed a high T2 lesion in the left putamen at age 3 and a right putamen lesion at age 6. Cerebrospinal fluid free thyroxine concentrations were low, with normal 3,3',5-triiodothyronine concentrations.     

Cognition and behavior at school entry in children with congenital hypothyroidism treated early with high-dose levothyroxine

OBJECTIVE: To document cognition and behavior at school entry in these patients.Study design Eighteen children with congenital hypothyroidism (CH; 9 severe and 9 moderate, based on a surface of the knee epiphyses at diagnosisor=0.05 cm(2)) treated from a median of 14 days with a median of 12.0 microg/kg per day of levothyroxine were evaluated at 5 years, 9 months, with the McCarthy Scale and the Questionnaire for Evaluation of Social Behavior, as were 40 control children. RESULTS: The global IQs at 5 years, 9 months, were similar: medians (range) were 102 (87 to 133), 102 (84 to 135), and 115 (88 to 136) (not significant) for severe CH, moderate CH, and control children, respectively. The behavioral scores of CH children were within the normal range. However, the number of times when plasma TSH was >6.0 mIU/L during treatment was correlated positively with anxiety (P=.02) and inattention (P=.05), whereas the number of times TSH was <0.8 mIU/L was correlated with lower verbal scores (P=.05). CONCLUSIONS: Children with severe CH treated early with a high dose of levothyroxine have normal global development and behavior at school entry.     

Neurodevelopmental outcomes in congenital hypothyroidism: comparison of initial T4 dose and time to reach target T4 and TSH

OBJECTIVES: To compare neurodevelopmental outcomes in severe and moderate congenital hypothyroidism (CH) among 3 different initial L-thyroxine doses and to examine the effect of the time to thyroid function normalization on neurodevelopmental outcomes. STUDY DESIGN: Neurodevelopmental assessments of 31 subjects included the Mullen Scales of Early Learning, Wechsler Preschool and Primary Scale of Intelligence-Revised, Wechsler Intelligence Scale for Children, Wide-Range Achievement Test, and Child Behavioral Checklist. RESULTS: Subjects started on higher initial L-thyroxine doses (50 mug) had full-scale IQ scores 11 points higher than those started on lower (37.5 mug) initial doses. However, verbal IQ, performance IQ, and achievement scores did not differ among the 3 treatment cohorts. Subjects with moderate CH had higher full-scale IQ scores than subjects with severe CH, regardless of the initial treatment dose. Subjects who took longer than 2 weeks to normalize thyroid function had significantly lower cognitive, attention, and achievement scores than those who achieved normal thyroid function at 1 or 2 weeks of therapy. CONCLUSIONS: Initial L-thyroxine dose and faster time to normalization of thyroid function are important to optimal neurodevelopmental outcome. In severe CH, it is important to choose an initial dose at the higher end of the recommended range to achieve these goals.     

Long-term follow-up of well-treated nephropathic cystinosis patients

We report the excellent clinical outcomes of siblings with nephropathic cystinosis treated diligently with cysteamine starting at 20 months and 2 months of age. Now 15 and 8 years old, they have glomerular filtration rates of 78 and 105 mL/min/1.73m 2 , respectively. These cases illustrate the critical importance of early diagnosis and treatment.     

VPS33B mutation with ichthyosis, cholestasis, and renal dysfunction but without arthrogryposis: incomplete ARC syndrome phenotype

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare multisystem disorder first described in 1979 and recently ascribed to mutation in VPS33B, whose product acts in intracellular trafficking. Arthrogryposis, spillage of various substances in the urine, and conjugated hyperbilirubinemia define an ARC core phenotype, in some patients associated with ichthyosis, central nervous system malformation, deafness, and platelet abnormalities. We describe a patient with cholestasis, aminoaciduria, ichthyosis, partial callosal agenesis, and sensorineural deafness who, although homozygous for the novel VPS33B mutation 971delA/K324fs, predicted to abolish VPS33B function, did not exhibit arthrogryposis. The phenotypes associated with VPS33B mutation may include incomplete ARC.