Radiological characteristics of skeletal growth in neonates and infants with achondroplasia.

Achondroplasia (ACH) is the most common form of skeletal dysplasia characterized by a rhizomelic short stature. Radiological skeletal findings in pediatric and adult patients with ACH include short long bones, a relatively longer fibula compared to the tibia, a narrow lumbar interpedicular distance, and a hypoplastic iliac wing. Nonetheless, the characteristics of skeletal growth during the neonatal and infantile periods have scarcely been explored. Therefore, this retrospective study aimed to analyze the radiological skeletal growth during the neonatal and infantile periods in 41 Japanese patients with genetically confirmed ACH. The length of long bones in the upper and lower limbs and the lumbar interpedicular distances at L1 and L4 were measured. These parameters showed significant positive correlations with age. The upper segment-to-lower segment ratio in the lower limbs resembled the data of healthy controls from previous reports. The L1/L4 and fibula/tibia ratios increased with age, suggesting that some representative skeletal phenotypes of ACH were less distinct during the neonatal and infantile periods. In conclusion, for the first time, this study radiologically characterized skeletal growth during the neonatal and infantile periods of patients with genetically confirmed ACH.

Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods.

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by pathogenic variants of cartilage oligomeric matrix protein (COMP). Clinical symptoms of PSACH are characterized by growth disturbances after the first year of life. These disturbances lead to severe short stature with short limbs, brachydactyly, scoliosis, joint laxity, joint pain since childhood, and a normal face. Epimetaphyseal dysplasia, shortened long bones, and short metacarpals and phalanges are common findings on radiological examination. Additionally, anterior tonguing of the vertebral bodies in the lateral view is an important finding in childhood because it is specific to PSACH and normalizes with age. Here, we report five Japanese patients with PSACH, with one recurrent (p.Cys351Tyr) and four novel heterozygous pathogenic COMP variants (p.Asp437Tyr, p.Asp446Gly, p.Asp507Tyr, and p.Asp518Val). These five pathogenic variants were located in the calcium-binding type 3 (T3) repeats. In four of the novel variants, the affected amino acid was aspartic acid, which is abundant in each of the eight T3 repeats. We describe the radiological findings of these five patients. We also retrospectively analyzed the sequential changes in the vertebral body and epimetaphysis of the long bones from the neonatal to infantile periods in a patient with PSACH and congenital heart disease.

A pediatric case of ureterolithiasis due to cystinuria accompanied by acute appendicitis; a case report.

INTRODUCTION: Acute abdominal pain, a chief complaint frequently seen in the emergency department, can be triggered by a vast range of conditions. Although ureterolithiasis is a less common cause in children, renal colic can be caused by calculi due to hereditary metabolic diseases among patients in those age groups. PRESENTATION OF CASE: We report a 12-year-old girl with abdominal pain who was diagnosed with concurrent acute appendicitis and ureterolithiasis due to cystinuria. Acute appendicitis was successfully treated with cefmetazole, and the calculus was eliminated after adequate fluid loading. DISCUSSION: Synchronous acute appendicitis and ureterolithiasis is reported to be rare. Cystinuria is a hereditary metabolic stone-forming disease, and the first calculi can be detected in childhood. Increasing the solubility of cystine in the urine is required to prevent recurrent stone formation and accompanying complications. Urinalysis, ultrasound, and computed tomography coincidentally demonstrated two different acute pathological processes of ureterolithiasis and appendicitis. CONCLUSION: Careful physical and laboratory examination can help clinicians find coexisting etiologies of acute abdominal pain. Ureterolithiasis can be seen in children with hereditary disorders such as cystinuria. Early diagnosis of cystinuria and close monitoring may lead to a better long-term outcome.

Coronary artery lesions and the increasing incidence of Kawasaki disease resistant to initial immunoglobulin.

BACKGROUNDS: Kawasaki disease (KD) is a systemic vasculitis of childhood involving coronary arteries. Treatment for intractable cases at a higher risk of cardiac sequelae remains controversial. METHODS: Clinical outcomes of KD patients diagnosed in Yamaguchi prefecture, Japan between 2003 and 2014 were analyzed using the medical records from all 14 hospitals covering the prefecture. The study included 1487 patients (male:female, 873:614; median age at diagnosis, 24months). RESULTS: The proportion of initial intravenous immunoglobulin (IVIG)-resistant patients increased from 7% to 23% during this decade, although no patients died. Twenty-four patients developed coronary artery lesions (CALs) over one month after the KD onset. The incidence of CAL in patients who received corticosteroid during the disease course (10/37; 27.0%) was higher than that in those who did not (14/1450; 0.97%, p=2.0×10(-35)). Nine patients who responded to initial IVIG plus corticosteroids had no CAL. Conversely, IVIG-resistant patients with alternate corticosteroid therapy more frequently developed CAL than those without it (10/28; 35.7% vs. 5/194; 2.6%, p=8.9×10(-10)). Multivariate analyses indicated corticosteroid therapy (p<0.0001), hyperbilirubinemia (p=0.0010), and a longer number of days before treatment (p=0.0005) as risk factors associated with CAL over a month after onset. The odds ratio of corticosteroid use increased from 18.3 to 43.5 if the cases were limited to initial IVIG non-responders and corticosteroid free-IVIG responders. CONCLUSIONS: IVIG-failure has recently increased. The incidence of CAL increased in intractable cases with prolonged corticosteroid use. Corticosteroid may not be alternate choice for IVIG-failure to reduce the risk of cardiac sequelae.

Analysis of linear growth in survivors of childhood acute lymphoblastic leukemia.

Therapy for childhood acute lymphoblastic leukemia (ALL) is entering a new era in terms of quality-of-life. In the current study, 21 patients with childhood-onset ALL were assessed for linear growth, bone mineral density (BMD), and endocrinological status, focusing especially on longitudinal analysis of the growth of each patient. Linear growth was uniformly attenuated during therapy in all patients. In contrast, after the cessation of therapy, the growth of each patient varied widely from attenuated to dramatic catch-up growth. In pubertal survivors who had received chemotherapy and cranial irradiation during prepuberty, the degree of growth after the cessation of therapy was negatively correlated with changes in height Z scores during therapy ( r = -0.76, P= 0.004). One of the factors involved in catch-up growth, urinary N-telopeptide/creatinine (U-NTx/Cr), was significantly higher in patients whose Z scores decreased after cessation of therapy ( P = 0.01), despite normal pubertal development and normal endocrinological assessments. The present study revealed individual differences in linear growth after the cessation of therapy and suggests the importance of catch-up growth during puberty.

Ultrasound assessment of tibial cortical bone acquisition in Japanese children and adolescents.

The purpose of the present study was to evaluate the normal process of cortical bone acquisition during childhood and adolescence, and the relationship between speed of sound (SOS), measured by the Sound Scan 2000 system, and linear growth. A total of 1689 healthy Japanese children and adolescents (862 males and 827 females, aged 7-19 years) were enrolled in the study. SOS (m/s) was measured at the right tibial midshaft and the standard SOS values in the children and adolescents were generated. Various growth parameters were also measured. SOS of tibia increased significantly with age in both males and females (P < 0.001 each). In both sexes, a spurt in SOS was noted 1 year after the standard age at which Japanese peak height velocity (PHV; cm/year) occurs, and SOS increased markedly after the age at which the length of tibia reached a maximum. Multiple regression equations for SOS were generated as a function of various growth parameters; for males, SOS = 3047 + 6.2 x height (cm) + 2.1 x weight (kg) - 9.8 x length of tibia (cm) (R2 = 0.50; P < 0.001) and for females, SOS = 2713 + 10.3 x height (cm) + 1.8 x weight (kg) - 15.5 x length of tibia (cm) (R2 = 0.49; P < 0.001). In both sexes, SOS correlated positively with body height and weight, but negatively with length of tibia. Our results indicate that SOS is quite useful for evaluating cortical bone status in children and adolescents; the results of these measurements may provide an explanation for the relative weakness of the mechanical properties of the bone during childhood and adolescence.