Testing and extending strategies for identifying genetic disease–related encounters in pediatric patients

Hypophosphatasia (HPP) is a rare genetic disease characterized by a decrease in the activity of tissue non-specific alkaline phosphatase (TNSALP). TNSALP is encoded by the ALPL gene, which is abundantly expressed in the skeleton, liver, kidney, and developing teeth. HPP exhibits high clinical variability largely due to the high allelic heterogeneity of the ALPL gene. HPP is characterized by multisystemic complications, although the most common clinical manifestations are those that occur in the skeleton, muscles, and teeth. These complications are mainly due to the accumulation of inorganic pyrophosphate (PPi) and pyridoxal-5′-phosphate (PLP). It has been observed that the prevalence of mild forms of the disease is more than 40 times the prevalence of severe forms. Patients with HPP present at least one mutation in the ALPL gene. However, it is known that there are other causes that lead to decreased alkaline phosphatase (ALP) levels without mutations in the ALPL gene. Although the phenotype can be correlated with the genotype in HPP, the prediction of the phenotype from the genotype cannot be made with complete certainty. The availability of a specific enzyme replacement therapy for HPP undoubtedly represents an advance in therapeutic strategy, especially in severe forms of the disease in pediatric patients.

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Current Approaches in Management of Patients with Hypophosphatasia

Педиатрическая фармакология ◽

10.15690/pf.v17i6.2202 ◽

2021 ◽

Vol 17 (6) ◽

pp. 519-528

Author(s):

Alexander A. Baranov ◽

Leyla S. Namazova-Baranova ◽

Sergey I. Kutsev ◽

Tea V. Margieva ◽

Nato D. Vashakmadze ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Genetic Disease ◽

Pediatric Patients ◽

Clinical Guideline ◽

Treatment Guidelines ◽

Differential Diagnostics ◽

Evidence Based ◽

Specific Alkaline Phosphatase ◽

Enzyme Replacement ◽

Based Medicine

he authors present the latest data on the hypophosphatasia (HPP) management in children. Hypophosphatasia is a rare genetic disease caused by deficiency of tissue-specific alkaline phosphatase due to mutation in the ALPL gene. The article covers all the features of epidemiology, etiology and pathogenesis, detailed stages of differential diagnostics. Treatment guidelines for pediatric patients are provided, they are based on the principles of evidence-based medicine. Special attention was given to the only effective method of hypophosphatasia management —enzyme replacement therapy (ERT). This material is the clinical guideline draft for the management of patients with hypophosphatasia prepared by the Union of Pediatricians of Russia and the Association of Medical Geneticists.

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The diagnostic trajectory of infants and children with clinical features of genetic disease

npj Genomic Medicine ◽

10.1038/s41525-021-00260-2 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Brock E. Schroeder ◽

Nina Gonzaludo ◽

Katie Everson ◽

Kyi-Sin Than ◽

Jeff Sullivan ◽

...

Keyword(s):

Genetic Testing ◽

Clinical Features ◽

Genetic Disease ◽

Pediatric Patients ◽

Genetic Disorders ◽

Genetic Diseases ◽

Cost Of Care ◽

Clinical Indicators ◽

Utilization Of Services ◽

Number Of Patients

AbstractWe characterized US pediatric patients with clinical indicators of genetic diseases, focusing on the burden of disease, utilization of genetic testing, and cost of care. Curated lists of diagnosis, procedure, and billing codes were used to identify patients with clinical indicators of genetic disease in healthcare claims from Optum’s de-identified Clinformatics® Database (13,076,038 unique patients). Distinct cohorts were defined to represent permissive and conservative estimates of the number of patients. Clinical phenotypes suggestive of genetic diseases were observed in up to 9.4% of pediatric patients and up to 44.7% of critically-ill infants. Compared with controls, patients with indicators of genetic diseases had higher utilization of services (e.g., mean NICU length of stay of 31.6d in a cohort defined by multiple congenital anomalies or neurological presentations compared with 10.1d for patients in the control population (P < 0.001)) and higher overall costs. Very few patients received any genetic testing (4.2–8.4% depending on cohort criteria). These results highlight the substantial proportion of the population with clinical features associated with genetic disorders and underutilization of genetic testing in these populations.

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Testing and extending recommended algorithms for identifying genetic disease-related encounters in pediatric patients

Molecular Genetics and Metabolism ◽

10.1016/s1096-7192(21)00608-9 ◽

2021 ◽

Vol 132 ◽

pp. S344

Author(s):

Lisa Spees ◽

Laura Farnan ◽

Michael C. Adams ◽

Karen Hicklin ◽

Jeannette Bensen ◽

...

Keyword(s):

Genetic Disease ◽

Pediatric Patients

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Adolescent Congenital Central Hypoventilation Syndrome: An Easily Overlooked Diagnosis

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph182413402 ◽

2021 ◽

Vol 18 (24) ◽

pp. 13402

Author(s):

Marta Ditmer ◽

Szymon Turkiewicz ◽

Agata Gabryelska ◽

Marcin Sochal ◽

Piotr Białasiewicz

Keyword(s):

Genetic Disease ◽

Pediatric Patients ◽

Late Onset ◽

Current Knowledge ◽

Adolescent Female ◽

Congenital Central Hypoventilation Syndrome ◽

Respiratory Drive ◽

Central Hypoventilation ◽

Hypoventilation Syndrome ◽

Made In

Congenital central hypoventilation syndrome (CCHS), also known as Ondine’s curse, is a rare, potentially fatal genetic disease, manifesting as a lack of respiratory drive. Most diagnoses are made in pediatric patients, however late-onset cases have been rarely reported. Due to the milder symptoms at presentation that might easily go overlooked, these late-onset cases can result in serious health consequences later in life. Here, we present a case report of late-onset CCHS in an adolescent female patient. In this review we summarize the current knowledge about symptoms, as well as clinical management of CCHS, and describe in detail the molecular mechanism responsible for this disorder.

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Audiology Service Models in a Family Physician Practice Setting

Perspectives on Audiology ◽

10.1044/poa6.1.24 ◽

2010 ◽

Vol 6 (1) ◽

pp. 24-32 ◽

Cited By ~ 2

Author(s):

Sridhar Krishnamurti

Keyword(s):

Pediatric Patients ◽

Practice Patterns ◽

Healthcare Delivery ◽

Direct Consequence ◽

Direct Access ◽

Practice Setting ◽

Pediatric Populations ◽

Family Practice Physicians ◽

Primary Focus ◽

Balance Problems

This article illustrates the potential of placing audiology services in a family physician’s practice setting to increase referrals of geriatric and pediatric patients to audiologists. The primary focus of family practice physicians is the diagnosis/intervention of critical systemic disorders (e.g., cardiovascular disease, diabetes, cancer). Hence concurrent hearing/balance disorders are likely to be overshadowed in such patients. If audiologists get referrals from these physicians and have direct access to diagnose and manage concurrent hearing/balance problems in these patients, successful audiology practice patterns will emerge, and there will be increased visibility and profitability of audiological services. As a direct consequence, audiological services will move into the mainstream of healthcare delivery, and the profession of audiology will move further towards its goals of early detection and intervention for hearing and balance problems in geriatric and pediatric populations.

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